WEBVTT 00:00:00.000 --> 00:00:01.994 align:middle line:90% [SQUEAKING] 00:00:01.994 --> 00:00:03.488 align:middle line:90% [RUSTLING] 00:00:03.488 --> 00:00:04.982 align:middle line:90% [CLICKING] 00:00:04.982 --> 00:00:10.960 align:middle line:90% 00:00:10.960 --> 00:00:12.440 align:middle line:90% JOSH MCDERMOTT: We made it. 00:00:12.440 --> 00:00:14.640 align:middle line:84% It's the last lecture of the term. 00:00:14.640 --> 00:00:16.140 align:middle line:84% I hope everybody's hanging in there. 00:00:16.140 --> 00:00:19.320 align:middle line:84% I know it's a little bit of a hectic time. 00:00:19.320 --> 00:00:22.160 align:middle line:84% Today we're going to talk about the sense of smell 00:00:22.160 --> 00:00:26.320 align:middle line:84% and the sense of taste, which are fairly related. 00:00:26.320 --> 00:00:29.820 align:middle line:84% Scientific terms for that is olfaction and gustation. 00:00:29.820 --> 00:00:32.667 align:middle line:84% So these are really interesting senses. 00:00:32.667 --> 00:00:35.000 align:middle line:84% They're kind of an important part of a lot of the things 00:00:35.000 --> 00:00:38.120 align:middle line:84% we care a lot about in life, but they're not nearly 00:00:38.120 --> 00:00:41.320 align:middle line:84% as well studied, especially in humans, 00:00:41.320 --> 00:00:44.960 align:middle line:84% as the other senses that we've been talking about so far. 00:00:44.960 --> 00:00:50.280 align:middle line:84% So we'll talk about the sense of smell and the sense of taste. 00:00:50.280 --> 00:00:54.920 align:middle line:84% So the basic idea of smell is that there 00:00:54.920 --> 00:01:00.350 align:middle line:84% are odorants that are given off by substances in the world. 00:01:00.350 --> 00:01:04.590 align:middle line:84% So the term "odor" refers to the sensation of smell, 00:01:04.590 --> 00:01:06.170 align:middle line:90% and it's caused by an odorant. 00:01:06.170 --> 00:01:10.470 align:middle line:84% So an odorant is a molecule that produces the sensation of smell. 00:01:10.470 --> 00:01:13.753 align:middle line:84% So for a molecule to be smelled, the odorant has to be volatile. 00:01:13.753 --> 00:01:15.670 align:middle line:84% So it has to be able to float through the air. 00:01:15.670 --> 00:01:17.070 align:middle line:90% It's got to be small. 00:01:17.070 --> 00:01:19.590 align:middle line:84% It's got to be hydrophobic, repellent to water. 00:01:19.590 --> 00:01:22.530 align:middle line:84% But not all such molecules can be smelled. 00:01:22.530 --> 00:01:25.710 align:middle line:84% So a famous example is carbon monoxide. 00:01:25.710 --> 00:01:28.390 align:middle line:84% So most people have carbon monoxide detectors or alarms 00:01:28.390 --> 00:01:33.490 align:middle line:84% in the places where they live because it's toxic, 00:01:33.490 --> 00:01:35.070 align:middle line:90% but it doesn't produce a smell. 00:01:35.070 --> 00:01:37.230 align:middle line:84% So you have to have an alarm that goes off. 00:01:37.230 --> 00:01:39.910 align:middle line:84% So we think these kinds of molecules 00:01:39.910 --> 00:01:44.670 align:middle line:84% were probably irrelevant when the odorant receptors evolved. 00:01:44.670 --> 00:01:47.430 align:middle line:84% So the sense of smell, it's obviously 00:01:47.430 --> 00:01:50.910 align:middle line:84% pretty important to humans in a lot of respects. 00:01:50.910 --> 00:01:53.910 align:middle line:84% We use it to evaluate lots of things. 00:01:53.910 --> 00:01:56.310 align:middle line:84% For some animal species, it's sometimes 00:01:56.310 --> 00:01:58.390 align:middle line:90% their most important sense. 00:01:58.390 --> 00:02:01.910 align:middle line:84% So it's well known that animals can track odorant signals 00:02:01.910 --> 00:02:03.050 align:middle line:90% over very long distances. 00:02:03.050 --> 00:02:04.383 align:middle line:90% This is a really famous picture. 00:02:04.383 --> 00:02:07.990 align:middle line:84% I think this is from National Geographic from a long time 00:02:07.990 --> 00:02:14.910 align:middle line:84% ago, where there's a dog and a bird that 00:02:14.910 --> 00:02:16.670 align:middle line:90% was dragged across a field. 00:02:16.670 --> 00:02:19.510 align:middle line:84% And the dog has some lights on its collar. 00:02:19.510 --> 00:02:22.530 align:middle line:90% So this is a time-lapse photo. 00:02:22.530 --> 00:02:24.150 align:middle line:84% So there's a yellow trace here that 00:02:24.150 --> 00:02:28.030 align:middle line:84% shows the path over which the bird was 00:02:28.030 --> 00:02:29.470 align:middle line:90% dragged across this field. 00:02:29.470 --> 00:02:32.910 align:middle line:84% And then the dog was trained to find animals, 00:02:32.910 --> 00:02:34.490 align:middle line:90% like in the context of hunting. 00:02:34.490 --> 00:02:39.210 align:middle line:84% And so you can see the track of the dog over time. 00:02:39.210 --> 00:02:42.930 align:middle line:84% And so it's following the scent trace back and forth. 00:02:42.930 --> 00:02:45.790 align:middle line:84% So initially, it runs around until it 00:02:45.790 --> 00:02:47.910 align:middle line:84% finds some hint of the smell, and then it kind of 00:02:47.910 --> 00:02:48.970 align:middle line:90% is able to follow this. 00:02:48.970 --> 00:02:50.970 align:middle line:84% And so dogs are really good at this. 00:02:50.970 --> 00:02:54.310 align:middle line:84% And you've probably heard about this 00:02:54.310 --> 00:02:56.760 align:middle line:84% being done in the context of police work and stuff, 00:02:56.760 --> 00:03:00.540 align:middle line:84% and they've been doing this for millennia. 00:03:00.540 --> 00:03:03.340 align:middle line:90% So animals do this a lot. 00:03:03.340 --> 00:03:05.000 align:middle line:84% People can do this to some extent. 00:03:05.000 --> 00:03:07.180 align:middle line:84% So this is kind of a crazy experiment that 00:03:07.180 --> 00:03:11.660 align:middle line:84% was done at UC Berkeley about 15 years ago, where they measured 00:03:11.660 --> 00:03:16.900 align:middle line:84% the ability of humans to track scents just using their noses. 00:03:16.900 --> 00:03:19.100 align:middle line:84% And so the way that they did this was-- it's 00:03:19.100 --> 00:03:22.340 align:middle line:84% inspired, obviously, by that classic photo of the dog, where 00:03:22.340 --> 00:03:25.660 align:middle line:84% there was a chemical that was kind of dragged 00:03:25.660 --> 00:03:26.720 align:middle line:90% across the field. 00:03:26.720 --> 00:03:27.980 align:middle line:90% That's the yellow line. 00:03:27.980 --> 00:03:31.120 align:middle line:84% So I think they used the smell of chocolate or something. 00:03:31.120 --> 00:03:37.720 align:middle line:84% And then the person was given the task of following the scent. 00:03:37.720 --> 00:03:41.140 align:middle line:84% And so to make sure that they were only using their noses, 00:03:41.140 --> 00:03:42.728 align:middle line:90% they were blindfolded. 00:03:42.728 --> 00:03:44.520 align:middle line:84% And you can't really see this very clearly, 00:03:44.520 --> 00:03:46.483 align:middle line:90% but they're wearing earmuffs. 00:03:46.483 --> 00:03:48.400 align:middle line:84% And they're wearing these really thick mittens 00:03:48.400 --> 00:03:49.640 align:middle line:84% so they can't really feel anything. 00:03:49.640 --> 00:03:51.140 align:middle line:84% So basically, all that they could do 00:03:51.140 --> 00:03:54.620 align:middle line:90% was move or crawl and smell. 00:03:54.620 --> 00:04:00.860 align:middle line:84% And then the red trace is the position of the person's body 00:04:00.860 --> 00:04:02.680 align:middle line:84% as they're moving over the field. 00:04:02.680 --> 00:04:06.700 align:middle line:84% So people are able to do this to some extent. 00:04:06.700 --> 00:04:09.960 align:middle line:90% A lot more slowly than dogs. 00:04:09.960 --> 00:04:12.660 align:middle line:90% 00:04:12.660 --> 00:04:17.160 align:middle line:84% So the human olfactory apparatus resides in the nose. 00:04:17.160 --> 00:04:19.839 align:middle line:84% So the nose has a couple functions. 00:04:19.839 --> 00:04:21.899 align:middle line:84% It filters, warms, and humidifies the air 00:04:21.899 --> 00:04:22.980 align:middle line:90% that we breathe. 00:04:22.980 --> 00:04:24.500 align:middle line:90% So it's part of breathing. 00:04:24.500 --> 00:04:27.380 align:middle line:84% But it also contains olfactory receptors. 00:04:27.380 --> 00:04:31.620 align:middle line:84% And so the olfactory epithelium is a mucous membrane 00:04:31.620 --> 00:04:33.580 align:middle line:84% whose primary function is to detect odorants 00:04:33.580 --> 00:04:34.400 align:middle line:90% in the inhaled air. 00:04:34.400 --> 00:04:36.700 align:middle line:90% So this is a face. 00:04:36.700 --> 00:04:37.780 align:middle line:90% That's the nose. 00:04:37.780 --> 00:04:41.872 align:middle line:84% Here's a cut through the nose that 00:04:41.872 --> 00:04:43.080 align:middle line:90% shows the various structures. 00:04:43.080 --> 00:04:44.538 align:middle line:84% So you have these cavities in here. 00:04:44.538 --> 00:04:45.260 align:middle line:90% You inhale. 00:04:45.260 --> 00:04:47.700 align:middle line:84% The air kind comes in, containing odorants. 00:04:47.700 --> 00:04:50.900 align:middle line:84% The olfactory epithelium contains receptors. 00:04:50.900 --> 00:04:55.170 align:middle line:84% The receptors interact with odorants, 00:04:55.170 --> 00:04:57.330 align:middle line:84% and that creates signals that are then 00:04:57.330 --> 00:05:00.430 align:middle line:84% sent to the olfactory bulb and then on to the cortex. 00:05:00.430 --> 00:05:04.770 align:middle line:90% 00:05:04.770 --> 00:05:05.270 align:middle line:90% All right. 00:05:05.270 --> 00:05:09.570 align:middle line:84% So there's three types of cells in the olfactory epithelium. 00:05:09.570 --> 00:05:11.530 align:middle line:84% There's supporting cells that provide 00:05:11.530 --> 00:05:14.090 align:middle line:84% metabolic and physical support for the olfactory sensory 00:05:14.090 --> 00:05:14.910 align:middle line:90% neurons. 00:05:14.910 --> 00:05:17.010 align:middle line:84% There are basal cells, which are precursor cells 00:05:17.010 --> 00:05:18.310 align:middle line:90% to olfactory sensory neurons. 00:05:18.310 --> 00:05:20.970 align:middle line:84% So the olfactory sensory neurons are 00:05:20.970 --> 00:05:22.982 align:middle line:84% kind of constantly regenerating themselves. 00:05:22.982 --> 00:05:25.190 align:middle line:84% And there's the olfactory sensory neurons themselves. 00:05:25.190 --> 00:05:28.010 align:middle line:84% This is the main kind of cell type that does a lot of the work 00:05:28.010 --> 00:05:29.590 align:middle line:90% that you think of as smell. 00:05:29.590 --> 00:05:32.710 align:middle line:90% So they're small neurons. 00:05:32.710 --> 00:05:36.890 align:middle line:84% They're located beneath a watery mucus layer in the epithelium. 00:05:36.890 --> 00:05:40.170 align:middle line:84% And then there are these cilia that kind of stick out 00:05:40.170 --> 00:05:42.090 align:middle line:90% that contain receptors. 00:05:42.090 --> 00:05:43.410 align:middle line:90% So you breathe in air. 00:05:43.410 --> 00:05:45.070 align:middle line:90% The air is wafting around here. 00:05:45.070 --> 00:05:46.470 align:middle line:90% It contains molecules. 00:05:46.470 --> 00:05:48.490 align:middle line:84% And then the molecules, in some way, 00:05:48.490 --> 00:05:51.850 align:middle line:84% are sensed by receptors on the cilia, 00:05:51.850 --> 00:05:53.970 align:middle line:84% and that changes the membrane potential 00:05:53.970 --> 00:05:55.630 align:middle line:90% in the olfactory sensory neuron. 00:05:55.630 --> 00:05:59.250 align:middle line:90% 00:05:59.250 --> 00:06:00.410 align:middle line:90% Yeah? 00:06:00.410 --> 00:06:03.310 align:middle line:84% AUDIENCE: Is that what the brain eating amoeba target? 00:06:03.310 --> 00:06:04.810 align:middle line:84% JOSH MCDERMOTT: Is that what, sorry? 00:06:04.810 --> 00:06:06.610 align:middle line:84% AUDIENCE: The brain-eating amoeba. 00:06:06.610 --> 00:06:08.490 align:middle line:84% JOSH MCDERMOTT: A brain-eating amoeba? 00:06:08.490 --> 00:06:10.490 align:middle line:84% Sorry, what about the brain-eating amoeba? 00:06:10.490 --> 00:06:12.298 align:middle line:90% AUDIENCE: Are those what target? 00:06:12.298 --> 00:06:14.090 align:middle line:84% JOSH MCDERMOTT: Are those what they target? 00:06:14.090 --> 00:06:15.548 align:middle line:84% AUDIENCE: I don't know if you know. 00:06:15.548 --> 00:06:18.170 align:middle line:84% JOSH MCDERMOTT: I didn't know about that, actually. 00:06:18.170 --> 00:06:21.363 align:middle line:84% They're supposed to target the olfactory receptor neurons? 00:06:21.363 --> 00:06:23.530 align:middle line:84% AUDIENCE: I just wondered how they get in the brain. 00:06:23.530 --> 00:06:26.370 align:middle line:90% JOSH MCDERMOTT: I see, I see. 00:06:26.370 --> 00:06:27.510 align:middle line:90% Could be. 00:06:27.510 --> 00:06:28.010 align:middle line:90% Yeah. 00:06:28.010 --> 00:06:30.030 align:middle line:90% I mean, this is-- 00:06:30.030 --> 00:06:31.530 align:middle line:84% I mean, these receptor neurons, they 00:06:31.530 --> 00:06:36.410 align:middle line:84% are kind of unusual in the sense that they're unprotected. 00:06:36.410 --> 00:06:39.470 align:middle line:90% So they're not behind anything. 00:06:39.470 --> 00:06:43.130 align:middle line:84% So the hair cells in your ear are kind of 00:06:43.130 --> 00:06:44.510 align:middle line:90% inside this bony thing. 00:06:44.510 --> 00:06:47.388 align:middle line:84% The photoreceptors are inside the eye. 00:06:47.388 --> 00:06:49.180 align:middle line:84% So these things are kind of just out there. 00:06:49.180 --> 00:06:53.360 align:middle line:84% So yeah, I guess they're vulnerable. 00:06:53.360 --> 00:06:55.018 align:middle line:90% OK, so we got these cilia. 00:06:55.018 --> 00:06:57.560 align:middle line:84% There are these little things, kind of hair-like protrusions. 00:06:57.560 --> 00:07:02.480 align:middle line:84% And they contain the receptor sites for the odorant molecules. 00:07:02.480 --> 00:07:04.280 align:middle line:84% And the olfactory receptor is the region 00:07:04.280 --> 00:07:06.960 align:middle line:84% on the cilia where the odorant molecules bind. 00:07:06.960 --> 00:07:11.280 align:middle line:84% And so we'll talk in a second about how we think that works. 00:07:11.280 --> 00:07:13.000 align:middle line:84% Takes about seven or eight odor molecules 00:07:13.000 --> 00:07:15.960 align:middle line:84% binding to a receptor to initiate an action potential. 00:07:15.960 --> 00:07:17.440 align:middle line:84% So there's a lot of things that are 00:07:17.440 --> 00:07:20.440 align:middle line:84% different about the sense of smell compared to the senses 00:07:20.440 --> 00:07:22.240 align:middle line:84% that we have talked about so far. 00:07:22.240 --> 00:07:25.640 align:middle line:84% One big difference is that smell is slow. 00:07:25.640 --> 00:07:29.540 align:middle line:84% So this is a graph that shows an example of that. 00:07:29.540 --> 00:07:33.480 align:middle line:84% So here's an experiment where the experimenter had 00:07:33.480 --> 00:07:38.880 align:middle line:84% an electrode next to or patch-clamped to this olfactory 00:07:38.880 --> 00:07:40.480 align:middle line:90% sensory neuron. 00:07:40.480 --> 00:07:42.720 align:middle line:84% Yeah, I guess it's a patch-clamp recording. 00:07:42.720 --> 00:07:46.600 align:middle line:84% You spritz odorant around the cilia 00:07:46.600 --> 00:07:49.030 align:middle line:84% of the olfactory sensory neuron, and then 00:07:49.030 --> 00:07:53.070 align:middle line:84% you measure the change in the membrane potential over time. 00:07:53.070 --> 00:07:56.230 align:middle line:84% So you can see there at time 0, that's 00:07:56.230 --> 00:07:59.790 align:middle line:84% when the odorant is spritzed onto the cilia. 00:07:59.790 --> 00:08:03.250 align:middle line:84% And then there's a change in the response of the neuron. 00:08:03.250 --> 00:08:05.290 align:middle line:84% But the thing to notice here is the x-axis. 00:08:05.290 --> 00:08:06.570 align:middle line:90% So that's in seconds. 00:08:06.570 --> 00:08:11.430 align:middle line:84% So this change in the response has a time constant 00:08:11.430 --> 00:08:12.850 align:middle line:90% of five or six seconds. 00:08:12.850 --> 00:08:14.790 align:middle line:84% It's like an fMRI signal, which we 00:08:14.790 --> 00:08:18.930 align:middle line:84% think of as incredibly slow relative to neural activity. 00:08:18.930 --> 00:08:22.410 align:middle line:90% So smell is slow. 00:08:22.410 --> 00:08:25.070 align:middle line:84% And it's slow, presumably in part 00:08:25.070 --> 00:08:31.170 align:middle line:84% because the signal itself is probably very smooth in time. 00:08:31.170 --> 00:08:34.190 align:middle line:84% So odorants are there in the air. 00:08:34.190 --> 00:08:38.409 align:middle line:84% And you can't just kind of instantly get rid of an odorant. 00:08:38.409 --> 00:08:41.309 align:middle line:84% So it's dependent on-- the stimulus 00:08:41.309 --> 00:08:42.870 align:middle line:84% is dependent on airflow, and that 00:08:42.870 --> 00:08:44.530 align:middle line:90% makes it temporally sluggish. 00:08:44.530 --> 00:08:50.270 align:middle line:84% And so that's probably why this is the way that it is. 00:08:50.270 --> 00:08:52.310 align:middle line:84% So we got these olfactory sensory neurons 00:08:52.310 --> 00:08:53.590 align:middle line:90% with their receptors. 00:08:53.590 --> 00:08:57.390 align:middle line:84% And their axons go through this bony structure, 00:08:57.390 --> 00:08:58.930 align:middle line:90% called the cribriform plate. 00:08:58.930 --> 00:09:02.670 align:middle line:84% So it's a bone that's got all these holes in it that separates 00:09:02.670 --> 00:09:06.550 align:middle line:90% the nose from the brain. 00:09:06.550 --> 00:09:10.030 align:middle line:84% And this is the olfactory bulb where those signals project. 00:09:10.030 --> 00:09:14.030 align:middle line:84% So the consequence of this, because these receptors are just 00:09:14.030 --> 00:09:18.430 align:middle line:84% out there on the other side of this bone, 00:09:18.430 --> 00:09:20.650 align:middle line:84% is that you can lose your sense of smell 00:09:20.650 --> 00:09:22.590 align:middle line:90% if you get hit hard in the head. 00:09:22.590 --> 00:09:25.310 align:middle line:84% So there's lots of reasons why you should 00:09:25.310 --> 00:09:29.070 align:middle line:84% try not to hit your head, but one of them 00:09:29.070 --> 00:09:32.030 align:middle line:84% is that if you hit your head in the right way 00:09:32.030 --> 00:09:35.950 align:middle line:84% hard enough, that bone, that cribriform plate, kind of gets 00:09:35.950 --> 00:09:37.230 align:middle line:90% knocked. 00:09:37.230 --> 00:09:40.830 align:middle line:84% And it can slice off the olfactory sensory neurons 00:09:40.830 --> 00:09:45.560 align:middle line:84% and can cause anosmia, a profound loss of smell, 00:09:45.560 --> 00:09:48.340 align:middle line:84% which also impacts the sense of taste. 00:09:48.340 --> 00:09:50.340 align:middle line:84% So as we're going to discuss later, 00:09:50.340 --> 00:09:52.493 align:middle line:84% smell is not important just for smell, 00:09:52.493 --> 00:09:54.660 align:middle line:84% but also because it combines with the sense of taste 00:09:54.660 --> 00:09:57.080 align:middle line:84% to create flavor when you're eating food. 00:09:57.080 --> 00:10:00.740 align:middle line:90% 00:10:00.740 --> 00:10:04.100 align:middle line:84% So olfactory sensory neurons, they 00:10:04.100 --> 00:10:05.560 align:middle line:90% project to the olfactory bulb. 00:10:05.560 --> 00:10:07.060 align:middle line:84% It's about the size of a blueberry. 00:10:07.060 --> 00:10:09.393 align:middle line:90% It's just above the nose. 00:10:09.393 --> 00:10:11.560 align:middle line:84% It's where olfactory information is first processed. 00:10:11.560 --> 00:10:14.300 align:middle line:84% And there are two of them, one in each brain 00:10:14.300 --> 00:10:17.400 align:middle line:84% hemisphere corresponding to the left and the right nostrils. 00:10:17.400 --> 00:10:19.280 align:middle line:84% And the connections are ipsilateral. 00:10:19.280 --> 00:10:21.020 align:middle line:84% So in other words, the left nostril 00:10:21.020 --> 00:10:23.080 align:middle line:84% projects to the left olfactory bulb, 00:10:23.080 --> 00:10:28.340 align:middle line:84% and the right nostril projects to the right olfactory bulb. 00:10:28.340 --> 00:10:29.860 align:middle line:90% So you've got two nostrils. 00:10:29.860 --> 00:10:32.260 align:middle line:84% They project to different bits of the brain. 00:10:32.260 --> 00:10:35.660 align:middle line:84% And they get odorant input from different parts of space. 00:10:35.660 --> 00:10:40.220 align:middle line:84% So this is showing a velocity field 00:10:40.220 --> 00:10:42.620 align:middle line:90% of the air around the nose. 00:10:42.620 --> 00:10:45.620 align:middle line:84% And so you can see that the two nostrils 00:10:45.620 --> 00:10:49.820 align:middle line:84% are getting most of their input from different regions of space. 00:10:49.820 --> 00:10:52.680 align:middle line:84% So you might wonder, all right, what's that good for? 00:10:52.680 --> 00:10:57.060 align:middle line:84% We know that you benefit from having two ears. 00:10:57.060 --> 00:10:59.940 align:middle line:84% We've talked about how you benefit from having two eyes. 00:10:59.940 --> 00:11:04.220 align:middle line:84% What's the benefit from having two nostrils? 00:11:04.220 --> 00:11:08.300 align:middle line:84% Well, one measure of the effect of two nostrils 00:11:08.300 --> 00:11:12.700 align:middle line:84% came from this experiment of human scent tracking where, 00:11:12.700 --> 00:11:16.260 align:middle line:84% to investigate whether or not people use information 00:11:16.260 --> 00:11:21.620 align:middle line:84% from the two nostrils to help localize scents, 00:11:21.620 --> 00:11:23.940 align:middle line:84% they got rid of the two nostrils effectively, 00:11:23.940 --> 00:11:26.180 align:middle line:84% using what they call a nasal prism. 00:11:26.180 --> 00:11:28.740 align:middle line:84% So a nasal prism is this thing that you stick 00:11:28.740 --> 00:11:30.880 align:middle line:84% into your nostrils-- so that goes in one nostril, 00:11:30.880 --> 00:11:32.540 align:middle line:90% that goes to the other-- 00:11:32.540 --> 00:11:34.940 align:middle line:84% and the input comes from a single aperture 00:11:34.940 --> 00:11:40.450 align:middle line:84% as opposed to-- this is the control apparatus where, 00:11:40.450 --> 00:11:42.270 align:middle line:84% again, you stick something up your nose. 00:11:42.270 --> 00:11:44.090 align:middle line:84% But now, the two nostrils are still 00:11:44.090 --> 00:11:46.650 align:middle line:84% getting input from two different regions of space. 00:11:46.650 --> 00:11:49.840 align:middle line:84% And so the question is, well, if you're 00:11:49.840 --> 00:11:52.090 align:middle line:84% using the fact that the two nostrils are getting input 00:11:52.090 --> 00:11:55.610 align:middle line:84% from slightly different regions of space, that should show up 00:11:55.610 --> 00:11:57.890 align:middle line:90% in your ability to do stuff-- 00:11:57.890 --> 00:12:02.810 align:middle line:84% in this case, perform this scent tracking task. 00:12:02.810 --> 00:12:05.290 align:middle line:84% And that's what the results show. 00:12:05.290 --> 00:12:07.370 align:middle line:84% So these are two different measures 00:12:07.370 --> 00:12:12.475 align:middle line:84% of how well people could track scents across the grass. 00:12:12.475 --> 00:12:13.850 align:middle line:84% So this one is showing the number 00:12:13.850 --> 00:12:15.670 align:middle line:90% of runs that were completed. 00:12:15.670 --> 00:12:18.930 align:middle line:84% So I guess sometimes people just gave up. 00:12:18.930 --> 00:12:21.090 align:middle line:84% They lost track of the scent or something. 00:12:21.090 --> 00:12:23.370 align:middle line:84% So that's the number of runs completed. 00:12:23.370 --> 00:12:25.250 align:middle line:84% And this is the control, where you 00:12:25.250 --> 00:12:29.090 align:middle line:84% have effectively two nostrils, and this is the nasal prism. 00:12:29.090 --> 00:12:32.250 align:middle line:84% So you don't make it through the path as many times. 00:12:32.250 --> 00:12:37.270 align:middle line:84% And then this is how fast you can track scents. 00:12:37.270 --> 00:12:39.970 align:middle line:90% So meters per second squared. 00:12:39.970 --> 00:12:46.090 align:middle line:84% So the control is going about 24% faster than the people 00:12:46.090 --> 00:12:47.370 align:middle line:90% with the nasal prism. 00:12:47.370 --> 00:12:48.210 align:middle line:90% OK? 00:12:48.210 --> 00:12:49.290 align:middle line:90% All right. 00:12:49.290 --> 00:12:50.450 align:middle line:90% It kind of makes sense. 00:12:50.450 --> 00:12:51.212 align:middle line:90% Two nostrils. 00:12:51.212 --> 00:12:53.670 align:middle line:84% You have some ability to tell where smells are coming from. 00:12:53.670 --> 00:12:58.010 align:middle line:90% So that's part of the story. 00:12:58.010 --> 00:13:00.410 align:middle line:84% But just not to take this too seriously. 00:13:00.410 --> 00:13:04.230 align:middle line:84% Humans are pretty slow compared to a lot of animals. 00:13:04.230 --> 00:13:07.130 align:middle line:90% So if you look at-- 00:13:07.130 --> 00:13:08.890 align:middle line:90% so this is showing-- 00:13:08.890 --> 00:13:11.930 align:middle line:84% I guess they had people do this over multiple days. 00:13:11.930 --> 00:13:14.690 align:middle line:84% And so people do get better at this. 00:13:14.690 --> 00:13:17.510 align:middle line:84% But this is the mean velocity in meters per second squared. 00:13:17.510 --> 00:13:22.050 align:middle line:84% And so the absolute numbers here are very, very low. 00:13:22.050 --> 00:13:26.450 align:middle line:84% So 0.05 meters per second squared. 00:13:26.450 --> 00:13:30.050 align:middle line:90% It's very, very, very slow. 00:13:30.050 --> 00:13:33.810 align:middle line:84% But you can do it to some extent. 00:13:33.810 --> 00:13:38.040 align:middle line:84% So the olfactory bulb, an important structure 00:13:38.040 --> 00:13:42.920 align:middle line:84% in the processing of olfactory sensory information. 00:13:42.920 --> 00:13:46.160 align:middle line:84% The olfactory bulb contains these things called glomeruli. 00:13:46.160 --> 00:13:49.320 align:middle line:84% So these are these groups of cells 00:13:49.320 --> 00:13:53.360 align:middle line:84% that contain the axons of the olfactory sensory neurons 00:13:53.360 --> 00:13:55.480 align:middle line:90% of a particular type. 00:13:55.480 --> 00:13:59.680 align:middle line:84% And then the mitral cells are these output neurons 00:13:59.680 --> 00:14:02.480 align:middle line:84% that are contained within the olfactory bulb. 00:14:02.480 --> 00:14:04.040 align:middle line:84% So you have all of these axons that 00:14:04.040 --> 00:14:06.060 align:middle line:90% accumulate in this one place. 00:14:06.060 --> 00:14:08.260 align:middle line:84% And then the mitral cell gets input from that. 00:14:08.260 --> 00:14:10.980 align:middle line:84% And these are all of a certain type of receptor. 00:14:10.980 --> 00:14:13.060 align:middle line:84% And then that goes on to the rest of the brain. 00:14:13.060 --> 00:14:17.160 align:middle line:90% 00:14:17.160 --> 00:14:19.400 align:middle line:84% So the olfactory system is unusual 00:14:19.400 --> 00:14:21.000 align:middle line:84% relative to other senses in that it's 00:14:21.000 --> 00:14:23.458 align:middle line:84% the only one that doesn't go through the thalamus remember. 00:14:23.458 --> 00:14:27.040 align:middle line:84% So remember, the thalamus is kind of like this relay. 00:14:27.040 --> 00:14:30.680 align:middle line:84% And in vision, you go through the lateral geniculate nucleus. 00:14:30.680 --> 00:14:33.960 align:middle line:84% In hearing, you go through the medial geniculate nucleus. 00:14:33.960 --> 00:14:35.960 align:middle line:90% But smell doesn't do that. 00:14:35.960 --> 00:14:38.980 align:middle line:84% The olfactory bulb projects directly to the cortex. 00:14:38.980 --> 00:14:43.960 align:middle line:90% 00:14:43.960 --> 00:14:48.320 align:middle line:84% So normally, we think of primary sensory cortex 00:14:48.320 --> 00:14:51.822 align:middle line:84% as this distinct region that's typically-- 00:14:51.822 --> 00:14:53.280 align:middle line:84% primary sensory cortex is typically 00:14:53.280 --> 00:14:57.320 align:middle line:84% defined as the region-- as the site of the first projections 00:14:57.320 --> 00:14:59.260 align:middle line:84% onto the cortex within that sensory system. 00:14:59.260 --> 00:15:02.760 align:middle line:84% So we have primary auditory cortex, primary visual cortex, 00:15:02.760 --> 00:15:05.640 align:middle line:84% primary somatosensory cortex we just talked about. 00:15:05.640 --> 00:15:06.960 align:middle line:90% So primary olfactory cortex. 00:15:06.960 --> 00:15:08.543 align:middle line:84% It's defined in the same way, but it's 00:15:08.543 --> 00:15:10.360 align:middle line:84% a little bit different in that it's 00:15:10.360 --> 00:15:12.460 align:middle line:90% much less of a unified region. 00:15:12.460 --> 00:15:14.480 align:middle line:84% So it's different parts of the brain 00:15:14.480 --> 00:15:18.140 align:middle line:84% that we often associate with having different functions. 00:15:18.140 --> 00:15:21.260 align:middle line:84% So the amygdala, hippocampal complex, and entorhinal cortex, 00:15:21.260 --> 00:15:23.640 align:middle line:84% these are regions that classically are associated 00:15:23.640 --> 00:15:26.320 align:middle line:90% with emotion and memory. 00:15:26.320 --> 00:15:30.760 align:middle line:84% So there doesn't seem to be a dedicated primary sensory region 00:15:30.760 --> 00:15:34.070 align:middle line:84% for olfaction, unlike these other sensory systems, 00:15:34.070 --> 00:15:35.090 align:middle line:90% at least in humans. 00:15:35.090 --> 00:15:38.470 align:middle line:90% 00:15:38.470 --> 00:15:40.510 align:middle line:90% So a lot is known-- 00:15:40.510 --> 00:15:42.330 align:middle line:84% OK, just to step back for a second, 00:15:42.330 --> 00:15:44.413 align:middle line:84% we just finished talking about the sense of touch. 00:15:44.413 --> 00:15:46.550 align:middle line:84% And so we talked about how, in the sense of touch, 00:15:46.550 --> 00:15:49.410 align:middle line:84% a lot of what we know is about the receptors. 00:15:49.410 --> 00:15:51.127 align:middle line:84% So half of that lecture was essentially 00:15:51.127 --> 00:15:52.710 align:middle line:84% about the different types of receptors 00:15:52.710 --> 00:15:55.030 align:middle line:90% and what differentiates them. 00:15:55.030 --> 00:15:57.610 align:middle line:84% And the same is true with olfaction. 00:15:57.610 --> 00:16:01.230 align:middle line:84% So there's been a lot of work on understanding 00:16:01.230 --> 00:16:03.750 align:middle line:90% how the receptors work. 00:16:03.750 --> 00:16:06.330 align:middle line:84% And a lot is actually known about the genetic basis, 00:16:06.330 --> 00:16:07.710 align:middle line:90% which is pretty interesting. 00:16:07.710 --> 00:16:12.550 align:middle line:84% So Linda Buck and Richard Axel discovered that the genome 00:16:12.550 --> 00:16:17.130 align:middle line:84% contains about 1,000 different olfactory receptor genes, 00:16:17.130 --> 00:16:20.180 align:middle line:84% each of which codes for a single type of olfactory receptor. 00:16:20.180 --> 00:16:22.430 align:middle line:84% And so what's really interesting is that, essentially, 00:16:22.430 --> 00:16:26.670 align:middle line:84% all mammals have pretty much the same set of these 1,000 genes. 00:16:26.670 --> 00:16:29.650 align:middle line:84% But not all of the genes are active. 00:16:29.650 --> 00:16:35.180 align:middle line:84% Some of them are non-functional what are called pseudogenes. 00:16:35.180 --> 00:16:36.940 align:middle line:84% And this varies a lot across species. 00:16:36.940 --> 00:16:39.820 align:middle line:84% So you have the same base set of genes 00:16:39.820 --> 00:16:43.460 align:middle line:84% that code for the set of possible receptors. 00:16:43.460 --> 00:16:46.340 align:middle line:84% But some species only have a small subset of them 00:16:46.340 --> 00:16:47.940 align:middle line:90% and others have more. 00:16:47.940 --> 00:16:51.060 align:middle line:84% So in dogs and mice, which are organisms that we associate 00:16:51.060 --> 00:16:54.340 align:middle line:84% with having really exceptional senses of smell, 00:16:54.340 --> 00:16:56.760 align:middle line:84% there's only about 20% that are pseudogenes. 00:16:56.760 --> 00:17:01.820 align:middle line:84% So that would mean about 800 different unique receptor types. 00:17:01.820 --> 00:17:06.140 align:middle line:84% Whereas with humans, something like 60% to 70% are pseudogenes. 00:17:06.140 --> 00:17:10.140 align:middle line:84% So that leaves us with more like 300 or 400 receptor types. 00:17:10.140 --> 00:17:12.380 align:middle line:90% So not nearly as many receptors. 00:17:12.380 --> 00:17:13.960 align:middle line:84% And these vary from person to person. 00:17:13.960 --> 00:17:17.119 align:middle line:84% So every person has a different number of these pseudogenes, 00:17:17.119 --> 00:17:20.060 align:middle line:84% and this results in individual differences in sensitivity 00:17:20.060 --> 00:17:22.619 align:middle line:90% to smells. 00:17:22.619 --> 00:17:24.540 align:middle line:84% There are certain smells that are kind of well 00:17:24.540 --> 00:17:27.500 align:middle line:84% known to elicit big individual differences in terms 00:17:27.500 --> 00:17:32.020 align:middle line:84% of how sensitive people are, cilantro being one that's 00:17:32.020 --> 00:17:34.860 align:middle line:90% especially well known. 00:17:34.860 --> 00:17:39.020 align:middle line:84% So let's talk about how the receptors work. 00:17:39.020 --> 00:17:42.900 align:middle line:84% So there's been historically two main theories 00:17:42.900 --> 00:17:45.340 align:middle line:90% of how these receptors work. 00:17:45.340 --> 00:17:48.020 align:middle line:84% One is called shape-pattern theory. 00:17:48.020 --> 00:17:50.620 align:middle line:84% This is the current dominant biochemical 00:17:50.620 --> 00:17:55.340 align:middle line:84% theory for how receptors transduce odorants. 00:17:55.340 --> 00:17:58.820 align:middle line:84% So the idea here is that different scents-- 00:17:58.820 --> 00:18:04.760 align:middle line:84% depending on the compatibility of the odorant shape-- 00:18:04.760 --> 00:18:09.060 align:middle line:84% so the shape of the molecule and the shape of the receptor-- 00:18:09.060 --> 00:18:10.940 align:middle line:84% different scents activate different arrays 00:18:10.940 --> 00:18:14.780 align:middle line:84% of olfactory receptors in the olfactory epithelium. 00:18:14.780 --> 00:18:18.077 align:middle line:84% So the various arrays produce specific firing patterns 00:18:18.077 --> 00:18:19.660 align:middle line:84% in the olfactory bulb, which determine 00:18:19.660 --> 00:18:20.800 align:middle line:90% the scent that we perceive. 00:18:20.800 --> 00:18:24.660 align:middle line:84% So this is, again, a very simplistic schematic 00:18:24.660 --> 00:18:27.020 align:middle line:84% where we're actually depicting the different odorants 00:18:27.020 --> 00:18:30.370 align:middle line:84% with these geometric shapes and the odorant receptors 00:18:30.370 --> 00:18:32.623 align:middle line:84% as having different shapes as well. 00:18:32.623 --> 00:18:34.290 align:middle line:84% And the idea is that some of the odorant 00:18:34.290 --> 00:18:37.510 align:middle line:84% shapes kind of fit into the odorant receptors 00:18:37.510 --> 00:18:40.850 align:middle line:90% and would then cause a response. 00:18:40.850 --> 00:18:42.650 align:middle line:84% So here's, again, another kind of schematic 00:18:42.650 --> 00:18:43.750 align:middle line:90% of how this would work. 00:18:43.750 --> 00:18:46.750 align:middle line:84% So imagine that this is your olfactory epithelium. 00:18:46.750 --> 00:18:49.530 align:middle line:84% And you've got all of these different receptor types here. 00:18:49.530 --> 00:18:50.830 align:middle line:90% So here's one odorant. 00:18:50.830 --> 00:18:52.130 align:middle line:90% And here's another. 00:18:52.130 --> 00:18:54.010 align:middle line:90% Two different molecular shapes. 00:18:54.010 --> 00:18:57.890 align:middle line:84% And so this one can bind to those two receptors. 00:18:57.890 --> 00:19:00.250 align:middle line:84% And so you get this pattern of response 00:19:00.250 --> 00:19:02.170 align:middle line:90% in the olfactory epithelium. 00:19:02.170 --> 00:19:05.490 align:middle line:84% This one, because it could be oriented in different ways 00:19:05.490 --> 00:19:08.570 align:middle line:84% and has more complicated shape, could bind to these four. 00:19:08.570 --> 00:19:14.610 align:middle line:84% And so you'd get this pattern of response. 00:19:14.610 --> 00:19:17.250 align:middle line:84% So that's the current kind of way 00:19:17.250 --> 00:19:19.570 align:middle line:84% that people think about this, is that based 00:19:19.570 --> 00:19:22.970 align:middle line:84% on the molecular shape, there's binding to particular types 00:19:22.970 --> 00:19:24.930 align:middle line:90% of receptors. 00:19:24.930 --> 00:19:27.210 align:middle line:84% And now there's this other theory 00:19:27.210 --> 00:19:30.490 align:middle line:84% that has been popular at various other times 00:19:30.490 --> 00:19:35.090 align:middle line:84% during history, which proposes that every perceived smell has 00:19:35.090 --> 00:19:37.410 align:middle line:84% a different vibrational frequency, 00:19:37.410 --> 00:19:40.210 align:middle line:84% and that molecules that produce the same vibrational frequencies 00:19:40.210 --> 00:19:41.970 align:middle line:84% will smell the same, and that there's 00:19:41.970 --> 00:19:44.170 align:middle line:84% some mechanism by which the receptor can 00:19:44.170 --> 00:19:47.650 align:middle line:84% measure the vibrational frequencies of the molecule. 00:19:47.650 --> 00:19:52.410 align:middle line:84% And so this is something that was proposed a long time ago. 00:19:52.410 --> 00:19:55.210 align:middle line:84% 25 years ago, there was a scientist 00:19:55.210 --> 00:19:59.810 align:middle line:84% who became newly convinced of the merits of this theory 00:19:59.810 --> 00:20:02.850 align:middle line:84% and talked a lot about it, and it got a lot of attention, 00:20:02.850 --> 00:20:06.290 align:middle line:90% culminating in this paper here. 00:20:06.290 --> 00:20:09.890 align:middle line:84% So this paper is titled, "A psychophysical test 00:20:09.890 --> 00:20:12.290 align:middle line:84% of the vibration theory of olfaction." 00:20:12.290 --> 00:20:15.950 align:middle line:84% And it's by Andreas Keller and Leslie Vosshall. 00:20:15.950 --> 00:20:18.630 align:middle line:84% Leslie Vosshall is a scientist who-- 00:20:18.630 --> 00:20:20.630 align:middle line:84% currently, she does a lot of work on mosquitoes. 00:20:20.630 --> 00:20:24.330 align:middle line:84% So she's interested in what makes mosquitoes 00:20:24.330 --> 00:20:26.740 align:middle line:90% like want to bite humans. 00:20:26.740 --> 00:20:30.880 align:middle line:84% And it's important because they spread malaria and things 00:20:30.880 --> 00:20:32.440 align:middle line:90% like that. 00:20:32.440 --> 00:20:34.080 align:middle line:84% And what attracts mosquitoes to humans 00:20:34.080 --> 00:20:35.247 align:middle line:90% involves the sense of smell. 00:20:35.247 --> 00:20:39.527 align:middle line:84% So she's always been interested in olfaction. 00:20:39.527 --> 00:20:40.860 align:middle line:90% I'll just read you the abstract. 00:20:40.860 --> 00:20:41.720 align:middle line:90% So it says. 00:20:41.720 --> 00:20:43.800 align:middle line:84% "At present, no satisfactory theory 00:20:43.800 --> 00:20:46.440 align:middle line:84% exists to explain how a given molecule results 00:20:46.440 --> 00:20:48.600 align:middle line:84% in the perception of a particular smell. 00:20:48.600 --> 00:20:50.680 align:middle line:84% One theory is that olfactory sensory neurons 00:20:50.680 --> 00:20:54.280 align:middle line:84% detect intramolecular vibrations of the odorous molecule. 00:20:54.280 --> 00:20:57.200 align:middle line:84% We used psychophysical methods in humans to test this vibration 00:20:57.200 --> 00:21:00.260 align:middle line:84% theory of olfaction and found no evidence to support it." 00:21:00.260 --> 00:21:02.080 align:middle line:90% So that's the summary. 00:21:02.080 --> 00:21:07.440 align:middle line:84% So then the intro here describes a little bit of the context. 00:21:07.440 --> 00:21:10.440 align:middle line:84% So it says, "A book about physiologist Luca Turin"-- 00:21:10.440 --> 00:21:12.880 align:middle line:84% who's this person who tried to revive this theory, 00:21:12.880 --> 00:21:15.260 align:middle line:84% "reviewed previously in this journal and elsewhere, 00:21:15.260 --> 00:21:17.800 align:middle line:84% has generated new interest in the theory that the smell 00:21:17.800 --> 00:21:20.960 align:middle line:84% of a molecule is determined by intramolecular vibrations rather 00:21:20.960 --> 00:21:23.000 align:middle line:90% than by the molecule's shape. 00:21:23.000 --> 00:21:26.360 align:middle line:84% Vibration theory was introduced in the 1930s and was later 00:21:26.360 --> 00:21:29.680 align:middle line:84% extended, but no biological mechanism to convert molecular 00:21:29.680 --> 00:21:32.477 align:middle line:84% vibrations into neuronal activation was proposed. 00:21:32.477 --> 00:21:34.560 align:middle line:84% As a result, the theory has been largely neglected 00:21:34.560 --> 00:21:35.960 align:middle line:90% in the research community. 00:21:35.960 --> 00:21:39.480 align:middle line:84% In the 1990s, Turin proposed a transduction mechanism involving 00:21:39.480 --> 00:21:41.600 align:middle line:90% inelastic electron tunneling. 00:21:41.600 --> 00:21:45.020 align:middle line:84% Whether because of skepticism or scientific conspiracy, 00:21:45.020 --> 00:21:47.388 align:middle line:84% as alleged in the book and echoed in most reviews, 00:21:47.388 --> 00:21:49.680 align:middle line:84% his predictions have failed to generate empirical tests 00:21:49.680 --> 00:21:50.780 align:middle line:90% by other researchers. 00:21:50.780 --> 00:21:53.560 align:middle line:84% In the present study, we tested vibration theory's key 00:21:53.560 --> 00:21:55.600 align:middle line:90% psychophysical predictions." 00:21:55.600 --> 00:21:58.160 align:middle line:84% So essentially, the predictions are 00:21:58.160 --> 00:22:00.960 align:middle line:84% that certain things ought to smell like certain other things 00:22:00.960 --> 00:22:04.560 align:middle line:84% based on the molecular vibrations. 00:22:04.560 --> 00:22:06.320 align:middle line:90% And that's described here. 00:22:06.320 --> 00:22:09.520 align:middle line:84% So it says, "Turin predicts that the smell of a mixture 00:22:09.520 --> 00:22:12.160 align:middle line:90% of guaiacol"-- some chemical-- 00:22:12.160 --> 00:22:15.160 align:middle line:84% "and benzaldehyde"-- some other chemical-- 00:22:15.160 --> 00:22:19.360 align:middle line:84% "has a vanilla character not found in its components 00:22:19.360 --> 00:22:22.550 align:middle line:84% because the combined molecular vibrations of benzaldehyde 00:22:22.550 --> 00:22:26.430 align:middle line:84% and guaiacol approximate the vibrations of vanillin" 00:22:26.430 --> 00:22:28.750 align:middle line:84% which is what smells like vanilla. 00:22:28.750 --> 00:22:31.190 align:middle line:84% "To test this prediction, we asked subjects to rate 00:22:31.190 --> 00:22:33.790 align:middle line:84% the vanilla character of benzaldehyde, guaiacol, 00:22:33.790 --> 00:22:35.910 align:middle line:90% and a 1 to 1 mixture of both. 00:22:35.910 --> 00:22:38.630 align:middle line:84% Subjects were first familiarized with the individual stimuli 00:22:38.630 --> 00:22:41.790 align:middle line:84% at two different concentrations under non-blind conditions. 00:22:41.790 --> 00:22:44.790 align:middle line:84% In a subsequent test, vanillin at both concentrations was 00:22:44.790 --> 00:22:47.290 align:middle line:84% identified with an accuracy of 84%." 00:22:47.290 --> 00:22:49.070 align:middle line:84% So people were able to detect vanilla 00:22:49.070 --> 00:22:50.430 align:middle line:90% when it was actually there. 00:22:50.430 --> 00:22:51.070 align:middle line:90% OK. 00:22:51.070 --> 00:22:51.570 align:middle line:90% All right. 00:22:51.570 --> 00:22:54.790 align:middle line:84% So then they were "familiarized with this 13-point rating scale. 00:22:54.790 --> 00:22:59.390 align:middle line:84% 1 means no vanilla, and 13 means extremely vanilla." 00:22:59.390 --> 00:23:02.190 align:middle line:84% So this is a vanilla rating task. 00:23:02.190 --> 00:23:04.670 align:middle line:84% "Subjects rated the vanilla character of the individual 00:23:04.670 --> 00:23:07.750 align:middle line:84% components and the two- and three-component mixtures, 00:23:07.750 --> 00:23:09.350 align:middle line:90% presented in random order." 00:23:09.350 --> 00:23:09.910 align:middle line:90% OK. 00:23:09.910 --> 00:23:10.410 align:middle line:90% All right. 00:23:10.410 --> 00:23:12.150 align:middle line:90% So the results are shown here. 00:23:12.150 --> 00:23:16.870 align:middle line:84% So the bars here correspond to different odors, which 00:23:16.870 --> 00:23:19.840 align:middle line:84% are different combinations of vanillin, 00:23:19.840 --> 00:23:21.940 align:middle line:90% benzaldehyde, and guaiacol. 00:23:21.940 --> 00:23:26.380 align:middle line:84% And then the y-axis is plotting the vanilla rating 00:23:26.380 --> 00:23:29.260 align:middle line:84% from no vanilla to extremely vanilla. 00:23:29.260 --> 00:23:35.780 align:middle line:84% And so the vanilla on its own is rated as a 9. 00:23:35.780 --> 00:23:36.480 align:middle line:90% Pretty vanilla. 00:23:36.480 --> 00:23:36.980 align:middle line:90% OK. 00:23:36.980 --> 00:23:37.800 align:middle line:90% That's good. 00:23:37.800 --> 00:23:39.700 align:middle line:84% People are doing what they're supposed to do. 00:23:39.700 --> 00:23:43.190 align:middle line:84% These two chemicals on their own get very low ratings of vanilla. 00:23:43.190 --> 00:23:44.440 align:middle line:90% That's what's expected, right? 00:23:44.440 --> 00:23:46.300 align:middle line:84% And so the key prediction here is 00:23:46.300 --> 00:23:48.500 align:middle line:84% that the combination of these two things 00:23:48.500 --> 00:23:50.660 align:middle line:90% ought to smell like vanilla. 00:23:50.660 --> 00:23:52.940 align:middle line:84% But instead, it's getting a rating of 2. 00:23:52.940 --> 00:23:56.380 align:middle line:84% So no evidence that it smells like vanilla. 00:23:56.380 --> 00:23:59.615 align:middle line:84% If you add vanilla to any of these mixtures, 00:23:59.615 --> 00:24:01.240 align:middle line:84% then people say it smells like vanilla. 00:24:01.240 --> 00:24:03.460 align:middle line:84% But without vanilla, they don't say it. 00:24:03.460 --> 00:24:04.500 align:middle line:90% OK? 00:24:04.500 --> 00:24:05.040 align:middle line:90% OK. 00:24:05.040 --> 00:24:08.200 align:middle line:84% So this was an attempt to test this prediction. 00:24:08.200 --> 00:24:11.180 align:middle line:84% And they concluded that there's no evidence 00:24:11.180 --> 00:24:14.900 align:middle line:84% that this particular hypothesis is correct. 00:24:14.900 --> 00:24:15.400 align:middle line:90% All right. 00:24:15.400 --> 00:24:18.620 align:middle line:84% So that kind leaves us with this shape-pattern theory 00:24:18.620 --> 00:24:21.020 align:middle line:90% of olfactory receptors. 00:24:21.020 --> 00:24:24.220 align:middle line:84% So another piece of evidence that's relevant to this 00:24:24.220 --> 00:24:25.683 align:middle line:90% is stereoisomers. 00:24:25.683 --> 00:24:28.100 align:middle line:84% These are molecules that are mirror-image rotations of one 00:24:28.100 --> 00:24:28.980 align:middle line:90% another. 00:24:28.980 --> 00:24:31.580 align:middle line:84% So they have different shapes, but they 00:24:31.580 --> 00:24:35.100 align:middle line:84% contain the same atoms, and thus vibrate at the same frequencies. 00:24:35.100 --> 00:24:37.100 align:middle line:84% But they can smell completely different. 00:24:37.100 --> 00:24:38.720 align:middle line:90% So here's an example. 00:24:38.720 --> 00:24:40.200 align:middle line:90% These are two molecules. 00:24:40.200 --> 00:24:41.900 align:middle line:90% One of them smells like caraway. 00:24:41.900 --> 00:24:43.740 align:middle line:84% One of them smells like spearmint. 00:24:43.740 --> 00:24:45.300 align:middle line:84% So it's hard to know how you would 00:24:45.300 --> 00:24:47.383 align:middle line:84% explain that unless you have some mechanism that's 00:24:47.383 --> 00:24:48.720 align:middle line:90% based on shape. 00:24:48.720 --> 00:24:51.820 align:middle line:90% 00:24:51.820 --> 00:24:53.980 align:middle line:90% All right. 00:24:53.980 --> 00:24:59.940 align:middle line:84% Another important aspect of our olfactory experience 00:24:59.940 --> 00:25:01.200 align:middle line:90% is adaptation. 00:25:01.200 --> 00:25:04.980 align:middle line:84% So the sense of smell is very responsive to changes. 00:25:04.980 --> 00:25:07.980 align:middle line:84% So think about walking into a bakery where 00:25:07.980 --> 00:25:09.527 align:middle line:90% they've made fresh bread. 00:25:09.527 --> 00:25:11.860 align:middle line:84% And when you walk in, the sense that there's fresh bread 00:25:11.860 --> 00:25:12.840 align:middle line:90% is very, very strong. 00:25:12.840 --> 00:25:15.700 align:middle line:84% But then, over time, that kind of dissipates. 00:25:15.700 --> 00:25:19.210 align:middle line:84% Or you may know people who you think wear too much perfume. 00:25:19.210 --> 00:25:20.970 align:middle line:84% They presumably are not aware that they're 00:25:20.970 --> 00:25:22.610 align:middle line:84% wearing tons of perfume because they've 00:25:22.610 --> 00:25:25.330 align:middle line:90% adapted over time to the scent. 00:25:25.330 --> 00:25:31.570 align:middle line:84% So some adaptation is known to occur at the receptor level. 00:25:31.570 --> 00:25:34.970 align:middle line:84% So repeated exposure to an odorant 00:25:34.970 --> 00:25:37.850 align:middle line:84% causes the receptor to stop responding to the odorant 00:25:37.850 --> 00:25:39.800 align:middle line:90% or to respond less. 00:25:39.800 --> 00:25:41.550 align:middle line:84% And you can measure this psychophysically. 00:25:41.550 --> 00:25:45.410 align:middle line:84% So this is kind of a cool experiment where 00:25:45.410 --> 00:25:50.370 align:middle line:84% human participants were given an odorant to take home and have 00:25:50.370 --> 00:25:51.450 align:middle line:90% in their house. 00:25:51.450 --> 00:25:53.970 align:middle line:84% So they lived with this particular odorant 00:25:53.970 --> 00:25:56.050 align:middle line:84% for two weeks, just some chemical 00:25:56.050 --> 00:25:57.850 align:middle line:90% that has a particular smell. 00:25:57.850 --> 00:26:01.830 align:middle line:84% And then periodically, over time, 00:26:01.830 --> 00:26:03.970 align:middle line:90% they were brought into the lab. 00:26:03.970 --> 00:26:07.490 align:middle line:84% And the experimenters measured their detection thresholds. 00:26:07.490 --> 00:26:09.210 align:middle line:84% So the detection threshold for an odorant 00:26:09.210 --> 00:26:10.610 align:middle line:84% is the same as a detection threshold 00:26:10.610 --> 00:26:11.630 align:middle line:90% in some other modality. 00:26:11.630 --> 00:26:13.250 align:middle line:84% It's the concentration of the chemical 00:26:13.250 --> 00:26:15.810 align:middle line:84% that you need to have present for the person to be 00:26:15.810 --> 00:26:17.450 align:middle line:90% able to reliably detect it. 00:26:17.450 --> 00:26:18.858 align:middle line:84% And so you can measure that using 00:26:18.858 --> 00:26:20.650 align:middle line:84% the same kinds of psychophysical procedures 00:26:20.650 --> 00:26:23.510 align:middle line:84% that we've talked about repeatedly in this class. 00:26:23.510 --> 00:26:26.290 align:middle line:90% 00:26:26.290 --> 00:26:26.790 align:middle line:90% OK. 00:26:26.790 --> 00:26:30.350 align:middle line:84% So this is a graph that shows the detection thresholds-- 00:26:30.350 --> 00:26:32.130 align:middle line:90% that's on the y-axis-- 00:26:32.130 --> 00:26:32.990 align:middle line:90% over time. 00:26:32.990 --> 00:26:34.990 align:middle line:84% So these are different test sessions. 00:26:34.990 --> 00:26:37.890 align:middle line:84% And they're measuring the detection thresholds 00:26:37.890 --> 00:26:39.290 align:middle line:90% for two odorants. 00:26:39.290 --> 00:26:41.470 align:middle line:84% One is the one that the people had to live with. 00:26:41.470 --> 00:26:44.530 align:middle line:84% So that's the black dots, the adapting odorant. 00:26:44.530 --> 00:26:46.890 align:middle line:84% The other one is just a control odorant 00:26:46.890 --> 00:26:48.870 align:middle line:84% that they were repeatedly tested on, 00:26:48.870 --> 00:26:52.610 align:middle line:84% but that they did not get repeated exposure 00:26:52.610 --> 00:26:54.110 align:middle line:90% to apart from the experiment. 00:26:54.110 --> 00:26:58.050 align:middle line:84% And so the B1 and B2, those are baseline measurements. 00:26:58.050 --> 00:27:00.050 align:middle line:84% That's just when they brought them into the lab, 00:27:00.050 --> 00:27:02.370 align:middle line:84% before they sent them home with the scent. 00:27:02.370 --> 00:27:07.210 align:middle line:84% And then A1 and A2 are during the adaptation period, 00:27:07.210 --> 00:27:11.050 align:middle line:84% while the odor was in their home for those two weeks. 00:27:11.050 --> 00:27:15.660 align:middle line:84% And then the R1 through R4 is the recovery period. 00:27:15.660 --> 00:27:17.960 align:middle line:84% So that's when the odor was removed from the home. 00:27:17.960 --> 00:27:23.240 align:middle line:84% And they continued to test them, I think, once a week. 00:27:23.240 --> 00:27:24.040 align:middle line:90% OK. 00:27:24.040 --> 00:27:25.270 align:middle line:90% So what does this show? 00:27:25.270 --> 00:27:27.520 align:middle line:84% Well, if we just look at what happens with the control 00:27:27.520 --> 00:27:31.960 align:middle line:84% odorant, you can see that the thresholds decrease over time. 00:27:31.960 --> 00:27:35.660 align:middle line:84% So with repeated tests, the detection thresholds drop. 00:27:35.660 --> 00:27:38.040 align:middle line:84% So it's like people get better at detecting 00:27:38.040 --> 00:27:40.620 align:middle line:84% the scent that they're repeatedly being tested on. 00:27:40.620 --> 00:27:42.760 align:middle line:84% So that's just what normally happens 00:27:42.760 --> 00:27:45.220 align:middle line:84% if you test somebody a whole bunch of times in a row. 00:27:45.220 --> 00:27:50.760 align:middle line:84% And you can also see that in the baseline test, B1 and B2, 00:27:50.760 --> 00:27:53.920 align:middle line:84% the thresholds for the two odors are about the same. 00:27:53.920 --> 00:27:57.080 align:middle line:84% So the black and the white dots are pretty close. 00:27:57.080 --> 00:27:59.560 align:middle line:84% But then what you can see is that 00:27:59.560 --> 00:28:01.380 align:middle line:90% during the adaptation period-- 00:28:01.380 --> 00:28:03.560 align:middle line:84% this is when people are getting all this exposure 00:28:03.560 --> 00:28:05.360 align:middle line:90% to the adapting odorant-- 00:28:05.360 --> 00:28:07.200 align:middle line:90% the thresholds diverge. 00:28:07.200 --> 00:28:09.640 align:middle line:84% So the thresholds get substantially worse 00:28:09.640 --> 00:28:11.520 align:middle line:84% for the adapting odorant while they're 00:28:11.520 --> 00:28:13.880 align:middle line:84% kind of improving for the control odorant. 00:28:13.880 --> 00:28:16.840 align:middle line:84% And then the other thing that's pretty cool 00:28:16.840 --> 00:28:21.720 align:middle line:84% is that once you remove the chemical from the person's home, 00:28:21.720 --> 00:28:26.200 align:middle line:84% it takes three weeks for the sensitivity to the adapting odor 00:28:26.200 --> 00:28:30.000 align:middle line:84% to reach the same level as the control odor. 00:28:30.000 --> 00:28:31.040 align:middle line:90% OK. 00:28:31.040 --> 00:28:31.540 align:middle line:90% All right. 00:28:31.540 --> 00:28:35.720 align:middle line:84% So the consequence of this repeated exposure to something 00:28:35.720 --> 00:28:38.480 align:middle line:84% is changing the way that the people smell. 00:28:38.480 --> 00:28:41.360 align:middle line:90% And it lasts a while. 00:28:41.360 --> 00:28:48.380 align:middle line:84% So this is just a fact about adaptation to odors. 00:28:48.380 --> 00:28:50.400 align:middle line:90% It's kind of interesting. 00:28:50.400 --> 00:28:51.860 align:middle line:90% Any questions about that? 00:28:51.860 --> 00:29:01.160 align:middle line:90% 00:29:01.160 --> 00:29:02.040 align:middle line:90% OK. 00:29:02.040 --> 00:29:02.540 align:middle line:90% All right. 00:29:02.540 --> 00:29:07.480 align:middle line:84% So where does the adaptation happen? 00:29:07.480 --> 00:29:12.950 align:middle line:84% Well, there's evidence that it's happening at multiple stages. 00:29:12.950 --> 00:29:18.070 align:middle line:84% This is a graph that tries to get at this by measuring 00:29:18.070 --> 00:29:21.590 align:middle line:84% the extent to which adaptation transfers across nostrils. 00:29:21.590 --> 00:29:25.350 align:middle line:84% So remember, you've got two nostrils and two 00:29:25.350 --> 00:29:28.150 align:middle line:90% olfactory bulbs. 00:29:28.150 --> 00:29:31.750 align:middle line:84% And so in this experiment, the participants 00:29:31.750 --> 00:29:34.090 align:middle line:84% were subjected to unilateral adaptation. 00:29:34.090 --> 00:29:36.030 align:middle line:84% So there was some odor that was squirted up 00:29:36.030 --> 00:29:38.870 align:middle line:90% into one of the nostrils. 00:29:38.870 --> 00:29:41.510 align:middle line:84% And what is being measured in the experiment, 00:29:41.510 --> 00:29:43.990 align:middle line:84% before and after the adaptation, is 00:29:43.990 --> 00:29:48.750 align:middle line:84% ratings of odor magnitude at different odor concentrations. 00:29:48.750 --> 00:29:52.430 align:middle line:84% So we expect that as we increase the concentration 00:29:52.430 --> 00:29:56.230 align:middle line:84% of the odorant-- so there's more of these molecules in the air-- 00:29:56.230 --> 00:30:00.210 align:middle line:84% the odor magnitude is going to go up with some shape. 00:30:00.210 --> 00:30:04.510 align:middle line:84% And so the unadapted curve shows you the magnitude ratings 00:30:04.510 --> 00:30:08.510 align:middle line:84% for these odors just when you're not adapted. 00:30:08.510 --> 00:30:12.590 align:middle line:84% And then there are two conditions following adaptation. 00:30:12.590 --> 00:30:14.030 align:middle line:90% There's ipsilateral. 00:30:14.030 --> 00:30:16.270 align:middle line:84% So that means that you test people 00:30:16.270 --> 00:30:18.790 align:middle line:84% with the same nostril that has been adapted. 00:30:18.790 --> 00:30:21.690 align:middle line:84% So you squirt all this odor up into the left nostril, 00:30:21.690 --> 00:30:25.470 align:middle line:84% and then you test them for their odor magnitude 00:30:25.470 --> 00:30:26.602 align:middle line:90% on the left nostril. 00:30:26.602 --> 00:30:28.310 align:middle line:84% Then you can also test them on the right. 00:30:28.310 --> 00:30:31.550 align:middle line:84% And so what you're supposed to take away from the graph 00:30:31.550 --> 00:30:32.990 align:middle line:90% is two things. 00:30:32.990 --> 00:30:35.590 align:middle line:84% The first is that both of those graphs, the contralateral 00:30:35.590 --> 00:30:38.790 align:middle line:84% and ipsilateral, are below the unadapted. 00:30:38.790 --> 00:30:43.110 align:middle line:84% So there's some transfer of adaptation across nostrils. 00:30:43.110 --> 00:30:45.350 align:middle line:84% The second is that the ipsilateral is 00:30:45.350 --> 00:30:47.150 align:middle line:90% lower than the contralateral. 00:30:47.150 --> 00:30:49.270 align:middle line:84% And so the inference from that is 00:30:49.270 --> 00:30:52.310 align:middle line:84% that there's some central component to the adaptation, 00:30:52.310 --> 00:30:55.070 align:middle line:84% as well as some more peripheral component, at a stage where 00:30:55.070 --> 00:30:56.730 align:middle line:90% the two nostrils are separated. 00:30:56.730 --> 00:30:57.230 align:middle line:90% Yeah. 00:30:57.230 --> 00:30:59.490 align:middle line:84% AUDIENCE: Is it possible that during the adaptation, 00:30:59.490 --> 00:31:03.075 align:middle line:84% the molecules kind of traveled into the other nostril? 00:31:03.075 --> 00:31:03.950 align:middle line:90% JOSH MCDERMOTT: Yeah. 00:31:03.950 --> 00:31:05.510 align:middle line:84% So this is one of the reasons why 00:31:05.510 --> 00:31:07.780 align:middle line:84% I think these experiments are challenging, is 00:31:07.780 --> 00:31:12.820 align:middle line:84% that I think the most likely possibility is 00:31:12.820 --> 00:31:16.400 align:middle line:84% that-- so the odorant is squirted into the nostril. 00:31:16.400 --> 00:31:18.400 align:middle line:84% But then the person is breathing in and out. 00:31:18.400 --> 00:31:21.340 align:middle line:84% And so you exhale, and then you inhale. 00:31:21.340 --> 00:31:23.260 align:middle line:84% And so as some consequence of that, 00:31:23.260 --> 00:31:25.060 align:middle line:90% there could be some leakage. 00:31:25.060 --> 00:31:25.820 align:middle line:90% Yeah. 00:31:25.820 --> 00:31:26.700 align:middle line:90% So it's a little-- 00:31:26.700 --> 00:31:30.160 align:middle line:84% I don't know how to fully estimate the extent of that. 00:31:30.160 --> 00:31:34.840 align:middle line:84% And that's probably an asterisk surrounding the result. Yeah. 00:31:34.840 --> 00:31:35.340 align:middle line:90% Yeah. 00:31:35.340 --> 00:31:35.840 align:middle line:90% Yeah. 00:31:35.840 --> 00:31:38.860 align:middle line:90% These experiments are hard. 00:31:38.860 --> 00:31:39.960 align:middle line:90% Any other questions? 00:31:39.960 --> 00:31:47.100 align:middle line:90% 00:31:47.100 --> 00:31:51.620 align:middle line:84% So another thing that really is important with olfaction 00:31:51.620 --> 00:31:52.520 align:middle line:90% is hedonics. 00:31:52.520 --> 00:31:56.980 align:middle line:84% So some smells are nice, and some smells are not so nice. 00:31:56.980 --> 00:31:58.900 align:middle line:84% It's natural to wonder, what is it 00:31:58.900 --> 00:32:02.502 align:middle line:84% that makes the smells that are nice nice, 00:32:02.502 --> 00:32:04.210 align:middle line:84% and what is it that makes the smells that 00:32:04.210 --> 00:32:05.850 align:middle line:90% are not nice, not nice? 00:32:05.850 --> 00:32:09.050 align:middle line:84% And in particular, you might wonder 00:32:09.050 --> 00:32:10.930 align:middle line:84% whether the hedonic responses that we have 00:32:10.930 --> 00:32:12.810 align:middle line:90% are innate or learned. 00:32:12.810 --> 00:32:18.090 align:middle line:84% And there's probably components of both. 00:32:18.090 --> 00:32:21.090 align:middle line:84% So infant odor preferences, anecdotally, 00:32:21.090 --> 00:32:25.010 align:middle line:84% often seem to be very different from adults. 00:32:25.010 --> 00:32:28.090 align:middle line:84% There's also cross-cultural data that 00:32:28.090 --> 00:32:29.470 align:middle line:90% support associative learning. 00:32:29.470 --> 00:32:31.262 align:middle line:84% There's just all these examples that people 00:32:31.262 --> 00:32:34.610 align:middle line:84% know about of foods that, in some cultures, 00:32:34.610 --> 00:32:39.250 align:middle line:90% are considered to be delicacies. 00:32:39.250 --> 00:32:42.850 align:middle line:84% The example shown here is the Japanese food of natto. 00:32:42.850 --> 00:32:46.770 align:middle line:84% This is fermented soybeans that have a very, very strong odor. 00:32:46.770 --> 00:32:50.610 align:middle line:84% A lot of Westerners don't like the smell, 00:32:50.610 --> 00:32:54.690 align:middle line:84% but somebody who's from Japan, it's 00:32:54.690 --> 00:32:57.090 align:middle line:84% something that a lot of them enjoy, 00:32:57.090 --> 00:32:59.110 align:middle line:84% whereas a lot of the smell of cheese, 00:32:59.110 --> 00:33:03.010 align:middle line:84% which is something in the West that a lot of people enjoy, 00:33:03.010 --> 00:33:05.507 align:middle line:84% is considered disgusting by a lot of Japanese eaters. 00:33:05.507 --> 00:33:08.090 align:middle line:84% So there are these differences between cultures that everybody 00:33:08.090 --> 00:33:10.650 align:middle line:90% has probably experienced. 00:33:10.650 --> 00:33:13.570 align:middle line:84% But there's also some pretty interesting evidence 00:33:13.570 --> 00:33:16.537 align:middle line:84% that there's components of the perception of odor pleasantness 00:33:16.537 --> 00:33:17.870 align:middle line:90% that are shared across cultures. 00:33:17.870 --> 00:33:22.170 align:middle line:84% This is a pretty cool paper that came out fairly recently 00:33:22.170 --> 00:33:25.410 align:middle line:84% from the lab of Asifa Majid, who was our colloquium 00:33:25.410 --> 00:33:27.290 align:middle line:90% speaker just a few weeks ago. 00:33:27.290 --> 00:33:30.250 align:middle line:84% She does a lot of interesting cross-cultural research. 00:33:30.250 --> 00:33:32.930 align:middle line:84% And so what they did in this study 00:33:32.930 --> 00:33:37.610 align:middle line:84% is to test 10 different cultures that were quite diverse. 00:33:37.610 --> 00:33:41.810 align:middle line:84% Some hunter-gatherers and horticulturalists, as well as 00:33:41.810 --> 00:33:44.650 align:middle line:84% some people in the US and other places. 00:33:44.650 --> 00:33:47.930 align:middle line:84% And they had them smell a whole bunch of different odorants 00:33:47.930 --> 00:33:50.170 align:middle line:90% and then asked them-- 00:33:50.170 --> 00:33:53.730 align:middle line:84% and they asked them how pleasant they found the odors. 00:33:53.730 --> 00:33:56.330 align:middle line:84% So this is a picture that kind of 00:33:56.330 --> 00:34:00.600 align:middle line:84% shows the places where they ran these experiments. 00:34:00.600 --> 00:34:05.140 align:middle line:84% So they did one in Mexico and one in the US 00:34:05.140 --> 00:34:07.960 align:middle line:84% and then a bunch of different places 00:34:07.960 --> 00:34:10.300 align:middle line:84% that are all kind of hard to get to. 00:34:10.300 --> 00:34:14.600 align:middle line:90% 00:34:14.600 --> 00:34:21.000 align:middle line:90% And so here are the results. 00:34:21.000 --> 00:34:27.280 align:middle line:84% So there were about 10 different odors 00:34:27.280 --> 00:34:32.320 align:middle line:90% that participants had to smell. 00:34:32.320 --> 00:34:34.320 align:middle line:90% 10 odorants. 00:34:34.320 --> 00:34:36.679 align:middle line:84% And in every different culture, there 00:34:36.679 --> 00:34:38.100 align:middle line:90% was some number of individuals. 00:34:38.100 --> 00:34:42.080 align:middle line:84% Every individual is a column here. 00:34:42.080 --> 00:34:47.900 align:middle line:84% And the color is the ranking of the odor. 00:34:47.900 --> 00:34:52.100 align:middle line:84% So they ranked the odorants in order from most pleasant-- 00:34:52.100 --> 00:34:54.120 align:middle line:90% that's 1, that's in blue-- 00:34:54.120 --> 00:34:57.480 align:middle line:90% to least pleasant. 00:34:57.480 --> 00:35:03.360 align:middle line:84% And what you can see just from eyeballing it is vanillin 00:35:03.360 --> 00:35:08.240 align:middle line:90% is pretty blue across the board. 00:35:08.240 --> 00:35:12.920 align:middle line:84% So that's a smell that people generally like. 00:35:12.920 --> 00:35:16.640 align:middle line:84% And as you move up the plot, things kind of 00:35:16.640 --> 00:35:18.860 align:middle line:84% shift from being blue to being pretty red. 00:35:18.860 --> 00:35:22.000 align:middle line:90% 00:35:22.000 --> 00:35:24.920 align:middle line:84% And so the gestalt that you're supposed to take away from this 00:35:24.920 --> 00:35:28.720 align:middle line:84% is that each of the 10 cultures has 00:35:28.720 --> 00:35:33.460 align:middle line:84% fairly similar rankings of the pleasantness of these odorants. 00:35:33.460 --> 00:35:36.080 align:middle line:90% 00:35:36.080 --> 00:35:36.580 align:middle line:90% All right. 00:35:36.580 --> 00:35:40.280 align:middle line:84% So there's supposed to be some universal component 00:35:40.280 --> 00:35:43.960 align:middle line:90% to the evaluation of odors. 00:35:43.960 --> 00:35:47.320 align:middle line:84% And where that comes from and why is debatable, probably 00:35:47.320 --> 00:35:51.080 align:middle line:84% because odors provide a signal for things 00:35:51.080 --> 00:35:54.160 align:middle line:84% that are toxic or potentially have 00:35:54.160 --> 00:35:55.920 align:middle line:84% bacteria that you want to stay away from. 00:35:55.920 --> 00:36:00.310 align:middle line:84% But this is some evidence that there's some shared 00:36:00.310 --> 00:36:02.310 align:middle line:90% component to pleasantness. 00:36:02.310 --> 00:36:06.250 align:middle line:84% So that's the whirlwind tour of olfaction. 00:36:06.250 --> 00:36:09.830 align:middle line:84% Here's a summary of what we talked about olfaction. 00:36:09.830 --> 00:36:12.172 align:middle line:84% So the first thing is that there's lots of receptors. 00:36:12.172 --> 00:36:13.630 align:middle line:84% And I actually probably should have 00:36:13.630 --> 00:36:15.190 align:middle line:84% emphasized this a little bit more, 00:36:15.190 --> 00:36:22.055 align:middle line:90% which is that you can think of-- 00:36:22.055 --> 00:36:23.430 align:middle line:84% I mean, it's interesting to think 00:36:23.430 --> 00:36:24.950 align:middle line:84% about the number of different types of receptors 00:36:24.950 --> 00:36:26.290 align:middle line:90% that we have across the senses. 00:36:26.290 --> 00:36:30.810 align:middle line:84% And so, in vision, at least in photopic conditions, 00:36:30.810 --> 00:36:33.950 align:middle line:84% you have three cones if you have normal color vision. 00:36:33.950 --> 00:36:36.150 align:middle line:84% By comparison, olfaction in humans 00:36:36.150 --> 00:36:38.300 align:middle line:90% has got 300 receptor types. 00:36:38.300 --> 00:36:40.050 align:middle line:84% Of course, there's no spatial information. 00:36:40.050 --> 00:36:42.790 align:middle line:84% Well, minimal, because you have two nostrils. 00:36:42.790 --> 00:36:46.030 align:middle line:84% So much less spatial information but many, many more receptor 00:36:46.030 --> 00:36:46.530 align:middle line:90% types. 00:36:46.530 --> 00:36:49.030 align:middle line:84% So the receptor the space of receptor activation 00:36:49.030 --> 00:36:50.330 align:middle line:90% is very, very high dimensional. 00:36:50.330 --> 00:36:52.830 align:middle line:84% So that probably really changes the problem 00:36:52.830 --> 00:36:57.470 align:middle line:84% of estimating odors and separating odors and things 00:36:57.470 --> 00:36:58.070 align:middle line:90% like that. 00:36:58.070 --> 00:37:00.830 align:middle line:90% So there's lots of receptors. 00:37:00.830 --> 00:37:02.830 align:middle line:84% We believe that odorants bind to receptors 00:37:02.830 --> 00:37:04.390 align:middle line:90% based on molecular shape. 00:37:04.390 --> 00:37:05.910 align:middle line:84% The number of receptor types vary 00:37:05.910 --> 00:37:07.470 align:middle line:84% across species, again, in kind of the way 00:37:07.470 --> 00:37:08.387 align:middle line:90% that you would expect. 00:37:08.387 --> 00:37:10.150 align:middle line:84% So the species that we think have really 00:37:10.150 --> 00:37:11.830 align:middle line:84% exceptional senses of smell, that 00:37:11.830 --> 00:37:16.510 align:middle line:84% are very dependent on senses of smell, have more receptors. 00:37:16.510 --> 00:37:18.390 align:middle line:84% The general structure of the system 00:37:18.390 --> 00:37:20.750 align:middle line:84% is that the receptors project to glomeruli 00:37:20.750 --> 00:37:24.350 align:middle line:84% in the olfactory bulb, which then projects to the cortex. 00:37:24.350 --> 00:37:26.290 align:middle line:84% We talked about how responses are slow. 00:37:26.290 --> 00:37:28.950 align:middle line:84% So that's a difference between the olfactory system 00:37:28.950 --> 00:37:31.590 align:middle line:84% and the other sensory systems that we've talked about. 00:37:31.590 --> 00:37:34.750 align:middle line:84% We have some ability to localize smells based on the fact 00:37:34.750 --> 00:37:36.910 align:middle line:90% that we have two nostrils. 00:37:36.910 --> 00:37:38.790 align:middle line:84% There are strong effects of adaptation 00:37:38.790 --> 00:37:40.370 align:middle line:84% that happen on multiple time scales, 00:37:40.370 --> 00:37:43.310 align:middle line:90% including some over weeks. 00:37:43.310 --> 00:37:45.510 align:middle line:84% And there are effects of culture that 00:37:45.510 --> 00:37:49.070 align:middle line:84% are superimposed on a shared sense of pleasantness. 00:37:49.070 --> 00:37:50.230 align:middle line:90% OK. 00:37:50.230 --> 00:37:52.230 align:middle line:84% So gustation, or the sense of taste. 00:37:52.230 --> 00:37:52.730 align:middle line:90% All right. 00:37:52.730 --> 00:37:55.340 align:middle line:90% So here's the big picture. 00:37:55.340 --> 00:38:01.220 align:middle line:84% So when substances enter your mouth, either intentionally 00:38:01.220 --> 00:38:04.740 align:middle line:84% or unintentionally, molecules in the substances 00:38:04.740 --> 00:38:06.900 align:middle line:84% stimulate receptors in your tongue. 00:38:06.900 --> 00:38:09.340 align:middle line:84% The standard view is that there are four main receptor 00:38:09.340 --> 00:38:12.220 align:middle line:84% types that correspond to four basic tastes-- 00:38:12.220 --> 00:38:15.780 align:middle line:90% salty, sour, bitter, and sweet. 00:38:15.780 --> 00:38:18.000 align:middle line:84% Knowledge of the receptors is still evolving, 00:38:18.000 --> 00:38:21.260 align:middle line:84% but again, the study of taste is still primarily centered 00:38:21.260 --> 00:38:22.780 align:middle line:90% on the receptors. 00:38:22.780 --> 00:38:25.180 align:middle line:84% And activation of these taste receptors 00:38:25.180 --> 00:38:27.100 align:middle line:84% couples with olfactory stimulation 00:38:27.100 --> 00:38:28.880 align:middle line:90% when you eat to produce flavor. 00:38:28.880 --> 00:38:32.740 align:middle line:90% 00:38:32.740 --> 00:38:33.240 align:middle line:90% All right. 00:38:33.240 --> 00:38:36.760 align:middle line:84% So taste buds are embedded in papilla. 00:38:36.760 --> 00:38:38.940 align:middle line:90% These are bumps on your tongue. 00:38:38.940 --> 00:38:42.540 align:middle line:84% Each taste bud contains taste receptor cells. 00:38:42.540 --> 00:38:46.020 align:middle line:84% Information is sent to your brain via the cranial nerves. 00:38:46.020 --> 00:38:46.520 align:middle line:90% All right. 00:38:46.520 --> 00:38:47.900 align:middle line:90% That's the tongue. 00:38:47.900 --> 00:38:49.260 align:middle line:90% The tongue. 00:38:49.260 --> 00:38:52.570 align:middle line:84% All these nerves go up to your brain. 00:38:52.570 --> 00:38:55.350 align:middle line:84% Receptors are all over your tongue. 00:38:55.350 --> 00:38:57.890 align:middle line:90% 00:38:57.890 --> 00:39:01.870 align:middle line:84% Here's a picture that shows some of those taste buds. 00:39:01.870 --> 00:39:02.370 align:middle line:90% OK. 00:39:02.370 --> 00:39:03.990 align:middle line:84% Here's a close up of a taste bud. 00:39:03.990 --> 00:39:05.930 align:middle line:90% So that's a taste bud. 00:39:05.930 --> 00:39:09.830 align:middle line:84% And there are lots of these receptors in a given taste bud. 00:39:09.830 --> 00:39:10.330 align:middle line:90% So you eat. 00:39:10.330 --> 00:39:11.990 align:middle line:90% There are molecules in the food. 00:39:11.990 --> 00:39:14.750 align:middle line:84% They bind to receptors in the microvilli. 00:39:14.750 --> 00:39:16.338 align:middle line:84% So again, things kind of like cilia. 00:39:16.338 --> 00:39:18.130 align:middle line:84% Another example of these cells that kind of 00:39:18.130 --> 00:39:20.250 align:middle line:84% have something sticking out of them. 00:39:20.250 --> 00:39:21.770 align:middle line:90% It's got receptors. 00:39:21.770 --> 00:39:24.130 align:middle line:84% So your taste buds, they don't last very long 00:39:24.130 --> 00:39:25.850 align:middle line:90% but are constantly replenished. 00:39:25.850 --> 00:39:29.370 align:middle line:90% 00:39:29.370 --> 00:39:29.870 align:middle line:90% All right. 00:39:29.870 --> 00:39:32.270 align:middle line:84% So a tastant is kind of the analog of an odorant. 00:39:32.270 --> 00:39:34.890 align:middle line:84% So it's any stimulus that can be tasted. 00:39:34.890 --> 00:39:39.130 align:middle line:84% And we can divide tastants into two large categories. 00:39:39.130 --> 00:39:42.610 align:middle line:84% So some are made up of small charged particles, 00:39:42.610 --> 00:39:46.010 align:middle line:84% and those generally taste salty or sour. 00:39:46.010 --> 00:39:48.730 align:middle line:84% And in these cases, there are small ion channels 00:39:48.730 --> 00:39:53.370 align:middle line:84% within the microvilli that allow some types of charged particles 00:39:53.370 --> 00:39:54.790 align:middle line:90% to enter, but not others. 00:39:54.790 --> 00:39:56.530 align:middle line:84% And when those charged particles enter, 00:39:56.530 --> 00:39:58.230 align:middle line:84% it changes the membrane potential, 00:39:58.230 --> 00:40:04.050 align:middle line:84% and you have some sense that you've tasted something. 00:40:04.050 --> 00:40:04.550 align:middle line:90% OK. 00:40:04.550 --> 00:40:09.610 align:middle line:84% Other tastants are perceived via G protein-coupled receptors, 00:40:09.610 --> 00:40:11.830 align:middle line:84% similar to those in the olfactory system, 00:40:11.830 --> 00:40:15.410 align:middle line:84% where we think it's a function of the molecular shape 00:40:15.410 --> 00:40:16.970 align:middle line:90% binding to the receptor. 00:40:16.970 --> 00:40:21.090 align:middle line:84% And these are cases where the molecules taste sweet or bitter. 00:40:21.090 --> 00:40:25.650 align:middle line:84% So two broad classes of particles and receptor 00:40:25.650 --> 00:40:27.730 align:middle line:90% mechanisms-- 00:40:27.730 --> 00:40:30.410 align:middle line:84% salty and sour, where the molecules are small 00:40:30.410 --> 00:40:35.450 align:middle line:84% and they're charged and they pass through ion channels, 00:40:35.450 --> 00:40:39.050 align:middle line:84% and then sweet or bitter, where the molecules tend 00:40:39.050 --> 00:40:41.890 align:middle line:84% to be larger and have complicated shapes that 00:40:41.890 --> 00:40:45.890 align:middle line:84% determine their binding to particular receptors. 00:40:45.890 --> 00:40:48.400 align:middle line:84% So we're going to talk about each of these four 00:40:48.400 --> 00:40:51.520 align:middle line:90% types of receptors in turn. 00:40:51.520 --> 00:40:55.460 align:middle line:84% So salt is made up of two charged particles-- 00:40:55.460 --> 00:40:58.000 align:middle line:84% a cation with a positive charge and an anion 00:40:58.000 --> 00:40:59.500 align:middle line:90% with a negative charge. 00:40:59.500 --> 00:41:00.880 align:middle line:90% So here are some examples. 00:41:00.880 --> 00:41:04.400 align:middle line:84% So common table salt is sodium chloride. 00:41:04.400 --> 00:41:06.020 align:middle line:90% So sodium is the cation. 00:41:06.020 --> 00:41:09.760 align:middle line:90% Chloride is the anion. 00:41:09.760 --> 00:41:12.000 align:middle line:84% And the cation is the part that's 00:41:12.000 --> 00:41:15.000 align:middle line:90% responsible for the salty taste. 00:41:15.000 --> 00:41:18.000 align:middle line:84% So you eat some salt, and the sodium 00:41:18.000 --> 00:41:20.000 align:middle line:90% passes through an ion channel. 00:41:20.000 --> 00:41:21.920 align:middle line:84% You get enough of this inside the cell there's 00:41:21.920 --> 00:41:23.960 align:middle line:84% a change in the membrane potential. 00:41:23.960 --> 00:41:28.148 align:middle line:90% 00:41:28.148 --> 00:41:31.260 align:middle line:84% So things that taste sour, by contrast, 00:41:31.260 --> 00:41:33.280 align:middle line:90% come from acidic substances. 00:41:33.280 --> 00:41:35.640 align:middle line:84% So generally, acidity is proportional 00:41:35.640 --> 00:41:38.040 align:middle line:84% to the concentration of hydrogen ions. 00:41:38.040 --> 00:41:42.800 align:middle line:84% And so the taste of something sour is produced by hydrogen. 00:41:42.800 --> 00:41:44.960 align:middle line:84% So there's two main ways for hydrogen 00:41:44.960 --> 00:41:47.260 align:middle line:84% to get inside the receptor cell, which is shown here. 00:41:47.260 --> 00:41:50.560 align:middle line:84% So there's ion channels that are selective for hydrogen. They 00:41:50.560 --> 00:41:51.920 align:middle line:90% can pass through that. 00:41:51.920 --> 00:41:56.720 align:middle line:84% Or they can make their way inside the cell membrane. 00:41:56.720 --> 00:41:58.320 align:middle line:84% Either way, the sour taste is driven 00:41:58.320 --> 00:42:03.240 align:middle line:84% by the concentration of hydrogen inside the receptor. 00:42:03.240 --> 00:42:05.260 align:middle line:90% So salty and sour. 00:42:05.260 --> 00:42:07.360 align:middle line:84% Again, these small charged particles 00:42:07.360 --> 00:42:13.240 align:middle line:84% that pass into the receptor cell and change the concentration 00:42:13.240 --> 00:42:14.600 align:middle line:90% inside of it. 00:42:14.600 --> 00:42:15.100 align:middle line:90% All right. 00:42:15.100 --> 00:42:17.280 align:middle line:90% Bitter. 00:42:17.280 --> 00:42:22.360 align:middle line:84% Many substances that taste bitter are poisonous. 00:42:22.360 --> 00:42:23.960 align:middle line:84% We often can't really distinguish 00:42:23.960 --> 00:42:26.500 align:middle line:84% between the tastes of different bitter compounds, 00:42:26.500 --> 00:42:27.940 align:middle line:90% at least not very well. 00:42:27.940 --> 00:42:33.040 align:middle line:84% They all just taste bad, at least at first. 00:42:33.040 --> 00:42:37.840 align:middle line:84% The kind of current view of bitterness 00:42:37.840 --> 00:42:41.160 align:middle line:84% is that we have about 25 different bitter receptors. 00:42:41.160 --> 00:42:44.173 align:middle line:84% They each respond to different molecules 00:42:44.173 --> 00:42:46.090 align:middle line:84% and different combinations of those molecules. 00:42:46.090 --> 00:42:49.270 align:middle line:84% So the columns here are different receptors. 00:42:49.270 --> 00:42:54.030 align:middle line:84% The rows here are different things that taste bitter. 00:42:54.030 --> 00:42:56.750 align:middle line:84% And this indicates which of the receptors 00:42:56.750 --> 00:43:01.030 align:middle line:84% responds to which of these chemicals. 00:43:01.030 --> 00:43:04.250 align:middle line:84% Again, we believe this is a function of the molecular shape 00:43:04.250 --> 00:43:05.890 align:middle line:90% and what binds to what. 00:43:05.890 --> 00:43:08.400 align:middle line:90% 00:43:08.400 --> 00:43:13.630 align:middle line:84% And so the thought here is that because a lot of the things that 00:43:13.630 --> 00:43:17.190 align:middle line:84% are bitter are poisonous, we evolved the ability 00:43:17.190 --> 00:43:20.470 align:middle line:84% to detect all these different types of molecules 00:43:20.470 --> 00:43:23.550 align:middle line:84% based on their toxicity, but it wasn't really important to be 00:43:23.550 --> 00:43:24.690 align:middle line:90% able to distinguish them. 00:43:24.690 --> 00:43:27.065 align:middle line:84% You just want to know that you're not supposed to eat it. 00:43:27.065 --> 00:43:29.750 align:middle line:90% So spit it out if you taste it. 00:43:29.750 --> 00:43:34.710 align:middle line:84% And of course, in modern times, we 00:43:34.710 --> 00:43:37.350 align:middle line:84% leverage the fact that we have these bitter receptors when 00:43:37.350 --> 00:43:37.987 align:middle line:90% we cook. 00:43:37.987 --> 00:43:40.070 align:middle line:84% A lot of people actually like the taste of bitter. 00:43:40.070 --> 00:43:42.852 align:middle line:90% I like bitter things. 00:43:42.852 --> 00:43:44.310 align:middle line:84% But historically, that's presumably 00:43:44.310 --> 00:43:46.590 align:middle line:90% what they evolved for. 00:43:46.590 --> 00:43:47.090 align:middle line:90% All right. 00:43:47.090 --> 00:43:48.050 align:middle line:90% So that's bitterness. 00:43:48.050 --> 00:43:52.510 align:middle line:90% 00:43:52.510 --> 00:43:54.770 align:middle line:84% We've also got things that are sweet. 00:43:54.770 --> 00:43:59.190 align:middle line:84% So things that are sweet typically contain sugar. 00:43:59.190 --> 00:44:01.670 align:middle line:84% So there's glucose, which is the main source of energy 00:44:01.670 --> 00:44:03.110 align:middle line:90% for most animals. 00:44:03.110 --> 00:44:06.272 align:middle line:84% There's also fructose and sucrose, common table sugar, 00:44:06.272 --> 00:44:08.230 align:middle line:84% which is a combination of glucose and fructose. 00:44:08.230 --> 00:44:11.030 align:middle line:84% So in contrast to bitterness, we think 00:44:11.030 --> 00:44:13.990 align:middle line:84% that there's a relatively small number of receptors 00:44:13.990 --> 00:44:18.130 align:middle line:84% that's responsible for all of the perception of sweetness. 00:44:18.130 --> 00:44:21.270 align:middle line:84% And different sweeteners stimulate different parts 00:44:21.270 --> 00:44:22.550 align:middle line:90% of the receptors. 00:44:22.550 --> 00:44:26.302 align:middle line:84% And we think that artificial sweeteners kind of trick us 00:44:26.302 --> 00:44:28.510 align:middle line:84% by stimulating the receptor as well, even though they 00:44:28.510 --> 00:44:31.890 align:middle line:84% don't actually contain energy in the way that sugars do. 00:44:31.890 --> 00:44:34.870 align:middle line:90% 00:44:34.870 --> 00:44:35.370 align:middle line:90% All right. 00:44:35.370 --> 00:44:38.350 align:middle line:84% So here's an example of one of these G protein-coupled 00:44:38.350 --> 00:44:40.390 align:middle line:90% receptors. 00:44:40.390 --> 00:44:43.860 align:middle line:84% So you've got a binding site here. 00:44:43.860 --> 00:44:49.180 align:middle line:84% And the sweet molecules kind of fit into the receptors and then 00:44:49.180 --> 00:44:51.940 align:middle line:84% initiate a process by which you detect 00:44:51.940 --> 00:44:54.300 align:middle line:90% the presence of the molecule. 00:44:54.300 --> 00:44:54.800 align:middle line:90% All right. 00:44:54.800 --> 00:44:56.460 align:middle line:84% So like I said, we think that taste 00:44:56.460 --> 00:45:00.953 align:middle line:84% is a system for detecting nutrients and antinutrients. 00:45:00.953 --> 00:45:02.620 align:middle line:84% We think the sense of bitter probably is 00:45:02.620 --> 00:45:05.260 align:middle line:90% useful for signaling poisons. 00:45:05.260 --> 00:45:08.140 align:middle line:84% Sour is probably important for detecting acidic solutions that 00:45:08.140 --> 00:45:09.732 align:middle line:90% might harm the body. 00:45:09.732 --> 00:45:11.940 align:middle line:84% Sweet and salty are important because our bodies need 00:45:11.940 --> 00:45:13.640 align:middle line:90% sodium and sugar to survive. 00:45:13.640 --> 00:45:17.100 align:middle line:90% 00:45:17.100 --> 00:45:20.100 align:middle line:84% And you can again look at infants 00:45:20.100 --> 00:45:21.880 align:middle line:84% to get a little bit of a window into this. 00:45:21.880 --> 00:45:24.700 align:middle line:84% So infants' behavior and facial expressions 00:45:24.700 --> 00:45:26.460 align:middle line:84% reveal apparently innate preferences 00:45:26.460 --> 00:45:29.200 align:middle line:84% for certain kinds of foods or certain kinds of tastes. 00:45:29.200 --> 00:45:31.420 align:middle line:84% So you give a baby something sweet, 00:45:31.420 --> 00:45:33.260 align:middle line:84% and they make a facial expression indicate 00:45:33.260 --> 00:45:35.260 align:middle line:90% indicating a positive response. 00:45:35.260 --> 00:45:38.800 align:middle line:84% Give them something sour, they'll purse their lips. 00:45:38.800 --> 00:45:43.900 align:middle line:84% Bitter things will tend to cause them to spit things out. 00:45:43.900 --> 00:45:44.400 align:middle line:90% All right. 00:45:44.400 --> 00:45:47.305 align:middle line:84% So four main tastes, different kinds of receptors. 00:45:47.305 --> 00:45:49.180 align:middle line:84% How many people have heard of the possibility 00:45:49.180 --> 00:45:50.840 align:middle line:90% of a fifth taste? 00:45:50.840 --> 00:45:51.340 align:middle line:90% Yeah. 00:45:51.340 --> 00:45:51.840 align:middle line:90% OK. 00:45:51.840 --> 00:45:56.340 align:middle line:84% So this is kind of well known at this point, umami. 00:45:56.340 --> 00:46:01.500 align:middle line:84% So monosodium glutamate, or MSG, is a chemical that's 00:46:01.500 --> 00:46:05.660 align:middle line:90% often added to Asian food. 00:46:05.660 --> 00:46:10.260 align:middle line:84% It kind of got a bad rap, at least in the United States, 00:46:10.260 --> 00:46:12.500 align:middle line:90% as far as I can tell, unjustly. 00:46:12.500 --> 00:46:14.200 align:middle line:84% It's derived from natural sources 00:46:14.200 --> 00:46:17.740 align:middle line:84% and I don't think is actually associated with any health 00:46:17.740 --> 00:46:19.140 align:middle line:90% risks. 00:46:19.140 --> 00:46:22.100 align:middle line:84% And it makes things taste savory. 00:46:22.100 --> 00:46:26.760 align:middle line:84% So umami is the taste of things that are savory. 00:46:26.760 --> 00:46:32.140 align:middle line:84% And we believe that this is a function of glutamate. 00:46:32.140 --> 00:46:34.360 align:middle line:84% So glutamate is an important neurotransmitter. 00:46:34.360 --> 00:46:36.740 align:middle line:90% It's used throughout the brain. 00:46:36.740 --> 00:46:40.330 align:middle line:84% And so the general thinking is that glutamate receptors 00:46:40.330 --> 00:46:45.710 align:middle line:84% have been co-opted to augment the sense of taste. 00:46:45.710 --> 00:46:51.270 align:middle line:84% And you have foods that are high in glutamate, 00:46:51.270 --> 00:46:55.090 align:middle line:84% and that contributes to that sense of taste 00:46:55.090 --> 00:46:59.130 align:middle line:84% that you get for certain kinds of savory foods. 00:46:59.130 --> 00:47:03.730 align:middle line:84% So that's the deal with the receptors. 00:47:03.730 --> 00:47:07.610 align:middle line:90% The taste pathway is shown here. 00:47:07.610 --> 00:47:10.130 align:middle line:84% So the input from the taste receptors 00:47:10.130 --> 00:47:15.130 align:middle line:84% is carried up the cranial nerve to part of the thalamus. 00:47:15.130 --> 00:47:18.190 align:middle line:84% The thalamus projects to gustatory cortex, 00:47:18.190 --> 00:47:20.850 align:middle line:84% which lives in a part of the brain called the insula, which 00:47:20.850 --> 00:47:23.750 align:middle line:84% projects to the orbitofrontal cortex. 00:47:23.750 --> 00:47:28.210 align:middle line:90% 00:47:28.210 --> 00:47:32.590 align:middle line:84% So the insular cortex is the primary cortical processing area 00:47:32.590 --> 00:47:33.090 align:middle line:90% for taste. 00:47:33.090 --> 00:47:38.880 align:middle line:84% Again, that's where the taste input kind of first projects. 00:47:38.880 --> 00:47:44.105 align:middle line:84% Orbitofrontal cortex is in the frontal lobe, like it sounds. 00:47:44.105 --> 00:47:45.480 align:middle line:84% Receives projections from insular 00:47:45.480 --> 00:47:48.440 align:middle line:84% cortex, and it's involved in a whole bunch of stuff, including 00:47:48.440 --> 00:47:49.760 align:middle line:90% the sense of taste. 00:47:49.760 --> 00:47:52.800 align:middle line:84% And again, in contrast to what is 00:47:52.800 --> 00:47:54.440 align:middle line:84% known about other sensory systems 00:47:54.440 --> 00:47:56.600 align:middle line:84% in terms of what goes on in the cortex, 00:47:56.600 --> 00:47:59.320 align:middle line:84% we know much less, especially in humans, 00:47:59.320 --> 00:48:03.960 align:middle line:84% about cortical processing of smell and taste. 00:48:03.960 --> 00:48:05.620 align:middle line:84% Just a little bit about the pathways. 00:48:05.620 --> 00:48:09.400 align:middle line:90% 00:48:09.400 --> 00:48:13.720 align:middle line:84% So the other thing that's really cool about the sense of smell 00:48:13.720 --> 00:48:16.360 align:middle line:90% is its role in flavor. 00:48:16.360 --> 00:48:22.060 align:middle line:84% So anytime you eat something, the molecules in the food, 00:48:22.060 --> 00:48:24.000 align:middle line:84% they stimulate the taste receptors. 00:48:24.000 --> 00:48:27.760 align:middle line:84% But really, you've got maybe four or five types 00:48:27.760 --> 00:48:28.980 align:middle line:90% of taste receptors. 00:48:28.980 --> 00:48:32.760 align:middle line:84% So four or five dimensions of the response of the tongue, 00:48:32.760 --> 00:48:33.780 align:middle line:90% more or less. 00:48:33.780 --> 00:48:37.240 align:middle line:84% But in addition, as you're chewing the food, 00:48:37.240 --> 00:48:42.760 align:middle line:84% odorants are emitted by the stuff you're chewing, 00:48:42.760 --> 00:48:45.640 align:middle line:84% and they travel through the back of your throat 00:48:45.640 --> 00:48:48.020 align:middle line:84% and stimulate the olfactory epithelium. 00:48:48.020 --> 00:48:50.720 align:middle line:84% This is called retronasal olfaction. 00:48:50.720 --> 00:48:54.360 align:middle line:90% Through the retronasal passage. 00:48:54.360 --> 00:48:58.600 align:middle line:84% And so that's a huge component of flavor. 00:48:58.600 --> 00:49:03.400 align:middle line:84% So retronasal olfactory sensation. 00:49:03.400 --> 00:49:06.440 align:middle line:84% It refers to the sensation of an odor that 00:49:06.440 --> 00:49:09.460 align:middle line:84% is perceived when chewing or swallowing food 00:49:09.460 --> 00:49:13.640 align:middle line:84% force an odorant in the mouth up behind the palate into the nose. 00:49:13.640 --> 00:49:15.600 align:middle line:84% And so the really interesting thing 00:49:15.600 --> 00:49:17.760 align:middle line:84% is that these odor sensations are perceived 00:49:17.760 --> 00:49:22.960 align:middle line:84% as originating from the mouth, even though the actual contact 00:49:22.960 --> 00:49:25.200 align:middle line:84% of the odorant and the receptor occurs 00:49:25.200 --> 00:49:28.720 align:middle line:84% in the nose at the olfactory mucosa. 00:49:28.720 --> 00:49:33.310 align:middle line:84% And so flavor is the combination of what people refer to as true 00:49:33.310 --> 00:49:36.910 align:middle line:84% taste-- so sweet, salty, sour, bitter, maybe umami-- 00:49:36.910 --> 00:49:39.990 align:middle line:90% and then retronasal olfaction. 00:49:39.990 --> 00:49:44.790 align:middle line:84% And if you've ever had a cold and noticed that the food just 00:49:44.790 --> 00:49:47.430 align:middle line:84% doesn't quite taste as interesting, 00:49:47.430 --> 00:49:52.725 align:middle line:84% you will have seen the role of retronasal olfaction 00:49:52.725 --> 00:49:54.350 align:middle line:84% in flavor, which is really significant. 00:49:54.350 --> 00:49:57.190 align:middle line:84% So when you have a cold and your nose is stuffed up, 00:49:57.190 --> 00:49:58.490 align:middle line:90% you're missing that component. 00:49:58.490 --> 00:50:04.070 align:middle line:84% And so the sense of taste gets greatly impoverished. 00:50:04.070 --> 00:50:06.870 align:middle line:84% So you might wonder, what happens 00:50:06.870 --> 00:50:10.550 align:middle line:84% when we can't perceive taste but can still smell? 00:50:10.550 --> 00:50:12.910 align:middle line:84% So there are, again, patient cases that 00:50:12.910 --> 00:50:14.570 align:middle line:90% give some insight into this. 00:50:14.570 --> 00:50:16.750 align:middle line:84% So there have been patients where 00:50:16.750 --> 00:50:20.430 align:middle line:84% the taste nerves are damaged, but they have normal olfaction. 00:50:20.430 --> 00:50:24.190 align:middle line:84% And so in this particular case, the person could smell lasagna, 00:50:24.190 --> 00:50:25.568 align:middle line:90% but there was no flavor. 00:50:25.568 --> 00:50:27.110 align:middle line:84% So they would eat the lasagna, and it 00:50:27.110 --> 00:50:28.750 align:middle line:90% wouldn't taste like anything. 00:50:28.750 --> 00:50:31.670 align:middle line:84% And so you can do something similar in the lab, 00:50:31.670 --> 00:50:35.710 align:middle line:84% by anesthetizing the relevant nerves with lidocaine. 00:50:35.710 --> 00:50:37.830 align:middle line:84% So this is a branch of the cranial nerve 00:50:37.830 --> 00:50:41.550 align:middle line:84% that carries taste information from the anterior tongue. 00:50:41.550 --> 00:50:44.030 align:middle line:84% And you retain the ability to smell, 00:50:44.030 --> 00:50:46.670 align:middle line:84% but you don't get that sense of flavor. 00:50:46.670 --> 00:50:50.470 align:middle line:84% So somehow or another, the brain processes odors differently 00:50:50.470 --> 00:50:52.230 align:middle line:84% depending on whether they're coming 00:50:52.230 --> 00:50:55.750 align:middle line:84% from the nose or the mouth, even though it's the same receptors 00:50:55.750 --> 00:50:57.450 align:middle line:90% that are being stimulated. 00:50:57.450 --> 00:50:59.910 align:middle line:84% So presumably there's some process 00:50:59.910 --> 00:51:02.030 align:middle line:84% by which the stimulation of the taste 00:51:02.030 --> 00:51:05.430 align:middle line:84% receptors kind of integrates with the input 00:51:05.430 --> 00:51:06.850 align:middle line:90% from the olfactory receptors. 00:51:06.850 --> 00:51:11.310 align:middle line:84% And that gives you the sense of flavor. 00:51:11.310 --> 00:51:11.810 align:middle line:90% All right. 00:51:11.810 --> 00:51:16.750 align:middle line:84% So here's the big picture of gustation. 00:51:16.750 --> 00:51:19.292 align:middle line:84% Molecules stimulate receptors in the tongue. 00:51:19.292 --> 00:51:20.750 align:middle line:84% The standard view is that there are 00:51:20.750 --> 00:51:22.310 align:middle line:84% four receptor types that correspond 00:51:22.310 --> 00:51:24.070 align:middle line:90% to four basic tastes-- 00:51:24.070 --> 00:51:25.490 align:middle line:90% salty, sour, bitter, and sweet. 00:51:25.490 --> 00:51:27.390 align:middle line:84% Remember, with salty and sour, they're 00:51:27.390 --> 00:51:29.850 align:middle line:84% driven by small charged molecules that 00:51:29.850 --> 00:51:32.100 align:middle line:84% pass through ion channels and change the concentration 00:51:32.100 --> 00:51:33.740 align:middle line:90% inside the receptor. 00:51:33.740 --> 00:51:37.577 align:middle line:84% Bitter and sweet have receptors that 00:51:37.577 --> 00:51:39.160 align:middle line:84% are selective for the molecular shape, 00:51:39.160 --> 00:51:42.220 align:middle line:84% so particular kinds of molecules can bind to them. 00:51:42.220 --> 00:51:45.197 align:middle line:84% In the case of bitter, we've got a large set of receptors. 00:51:45.197 --> 00:51:47.780 align:middle line:84% We don't really differentiate the responses, at least not very 00:51:47.780 --> 00:51:48.780 align:middle line:90% much. 00:51:48.780 --> 00:51:52.300 align:middle line:84% In the case of sweet, there's a smaller number of receptors, 00:51:52.300 --> 00:51:56.620 align:middle line:84% and different types of sugars can 00:51:56.620 --> 00:51:58.420 align:middle line:84% bind to different parts of receptors. 00:51:58.420 --> 00:52:02.940 align:middle line:84% And artificial sweeteners can trick our sense of taste 00:52:02.940 --> 00:52:05.593 align:middle line:84% by binding to those same receptors. 00:52:05.593 --> 00:52:07.760 align:middle line:84% So the knowledge of the receptors is still evolving. 00:52:07.760 --> 00:52:10.820 align:middle line:84% That's kind of what we know right now. 00:52:10.820 --> 00:52:13.100 align:middle line:84% And then activation of the taste receptors 00:52:13.100 --> 00:52:18.180 align:middle line:84% couples with olfactory stimulation to produce flavor. 00:52:18.180 --> 00:52:18.920 align:middle line:90% All right. 00:52:18.920 --> 00:52:21.040 align:middle line:84% So that's the whirlwind tour of taste. 00:52:21.040 --> 00:52:23.780 align:middle line:84% So as I said, taste and smell, they're 00:52:23.780 --> 00:52:26.220 align:middle line:84% really interesting and important for life. 00:52:26.220 --> 00:52:30.580 align:middle line:84% And we don't know nearly as much about them as we should. 00:52:30.580 --> 00:52:32.480 align:middle line:84% And they would be fun things, I think, 00:52:32.480 --> 00:52:34.793 align:middle line:84% for someone to go make a career in. 00:52:34.793 --> 00:52:36.460 align:middle line:84% But there's, at present, not a whole lot 00:52:36.460 --> 00:52:41.180 align:middle line:84% of people who study these two modalities. 00:52:41.180 --> 00:52:43.060 align:middle line:90% The end. 00:52:43.060 --> 00:52:47.540 align:middle line:84% So this brings us to the conclusion of 9.35. 00:52:47.540 --> 00:52:49.680 align:middle line:84% And it's been great having all of you in class. 00:52:49.680 --> 00:52:52.900 align:middle line:84% I appreciated all of the questions. 00:52:52.900 --> 00:52:57.340 align:middle line:84% And I hope that this inspires you 00:52:57.340 --> 00:52:59.500 align:middle line:90% to learn more about perception. 00:52:59.500 --> 00:53:03.420 align:middle line:84% And if you're around next year, please drop by and tell me 00:53:03.420 --> 00:53:04.580 align:middle line:90% how you're doing. 00:53:04.580 --> 00:53:09.460 align:middle line:84% If you're a graduating senior, congratulations. 00:53:09.460 --> 00:53:13.500 align:middle line:84% Wish you all the best on your next endeavors. 00:53:13.500 --> 00:53:15.690 align:middle line:90% And I'll leave it at that. 00:53:15.690 --> 00:53:27.000 align:middle line:90%