1
00:00:00,090 --> 00:00:02,490
The following content is
provided under a Creative

2
00:00:02,490 --> 00:00:04,059
Commons license.

3
00:00:04,059 --> 00:00:06,330
Your support will help
MIT OpenCourseWare

4
00:00:06,330 --> 00:00:10,720
continue to offer high quality
educational resources for free.

5
00:00:10,720 --> 00:00:13,320
To make a donation or
view additional materials

6
00:00:13,320 --> 00:00:17,280
from hundreds of MIT courses,
visit MIT OpenCourseWare

7
00:00:17,280 --> 00:00:18,450
at ocw.mit.edu.

8
00:00:26,307 --> 00:00:27,640
HAZEL SIVE: Some good questions.

9
00:00:27,640 --> 00:00:29,400
Let's zip through quickly.

10
00:00:29,400 --> 00:00:32,200
Why can't an initial
depolarization travel along

11
00:00:32,200 --> 00:00:33,790
the length of the axon?

12
00:00:33,790 --> 00:00:36,010
Last time, we went
through in detail

13
00:00:36,010 --> 00:00:39,940
how a signal is transmitted
from the outside

14
00:00:39,940 --> 00:00:44,170
to the inside of the cell by
ion flux across the membrane,

15
00:00:44,170 --> 00:00:48,730
and then how that ion flux is
transmitted down the neuron.

16
00:00:48,730 --> 00:00:51,820
Remember that the ions entering
the cell are just ions.

17
00:00:51,820 --> 00:00:55,000
They'll diffuse away.

18
00:00:55,000 --> 00:00:58,480
And so the depolarization
kind of dissipates.

19
00:00:58,480 --> 00:01:00,810
And it then needs
to be regenerated.

20
00:01:00,810 --> 00:01:03,400
The action potential,
each small depolarization

21
00:01:03,400 --> 00:01:06,820
or the whole signal,
each small depolarization

22
00:01:06,820 --> 00:01:11,800
with a specific magnitude, the
reversal of membrane potential

23
00:01:11,800 --> 00:01:15,910
going from about minus 60
millivolts, negative inside,

24
00:01:15,910 --> 00:01:19,870
to plus 55 or 60
millivolts, positive inside.

25
00:01:19,870 --> 00:01:22,300
Each of those is an
action potential.

26
00:01:22,300 --> 00:01:23,764
And here is an interesting one.

27
00:01:23,764 --> 00:01:25,180
Why doesn't the
membrane potential

28
00:01:25,180 --> 00:01:28,270
stop at zero when sodium
rushes into the cell

29
00:01:28,270 --> 00:01:29,920
during an action
potential, which

30
00:01:29,920 --> 00:01:33,340
is what you'd expect if
sodium was just moving along

31
00:01:33,340 --> 00:01:35,290
its concentration radian?

32
00:01:35,290 --> 00:01:38,550
Because the potential's not
only governed by sodium influx.

33
00:01:38,550 --> 00:01:42,100
There are chloride ions outside
the cell and potassium ions

34
00:01:42,100 --> 00:01:45,040
inside over the duration
of the potential.

35
00:01:45,040 --> 00:01:47,480
And as we'll discuss
briefly in a moment,

36
00:01:47,480 --> 00:01:50,140
it's during the
rectification process

37
00:01:50,140 --> 00:01:52,120
that you go back
to zero, and then

38
00:01:52,120 --> 00:01:55,740
you reverse membrane
potential again.

39
00:01:55,740 --> 00:02:00,610
Well, let's move on
to Nervous System 2.

40
00:02:00,610 --> 00:02:11,910
And I want to cover two
things today, both of which

41
00:02:11,910 --> 00:02:15,610
connect with last lecture,
and then move on to our topic

42
00:02:15,610 --> 00:02:16,110
today.

43
00:02:18,680 --> 00:02:21,630
We've drawn the analogy
of the nervous system

44
00:02:21,630 --> 00:02:24,260
as a communication
system through the body

45
00:02:24,260 --> 00:02:27,180
where there are wires, there are
connections between the wires,

46
00:02:27,180 --> 00:02:30,600
and there are circuits
that need to be laid down.

47
00:02:30,600 --> 00:02:34,000
Today, we're mostly going to
talk about the connections.

48
00:02:34,000 --> 00:02:41,080
But I want to talk a little
more about pumps and channels.

49
00:02:47,280 --> 00:02:49,620
And then we're going to
talk about the connections

50
00:02:49,620 --> 00:02:55,655
between neurons, which
is also called synapses.

51
00:02:59,150 --> 00:03:04,730
Let's begin with a little
more about pumps and channels.

52
00:03:04,730 --> 00:03:08,520
And I want to briefly
summarize where

53
00:03:08,520 --> 00:03:11,700
we were with talking
about an action potential,

54
00:03:11,700 --> 00:03:15,200
and introduce one
last kind of pump--

55
00:03:15,200 --> 00:03:16,620
of channel, excuse me--

56
00:03:16,620 --> 00:03:19,720
that we didn't quite get to
at the end of last lecture.

57
00:03:19,720 --> 00:03:22,530
And then we'll talk about the
pumps and channels involved

58
00:03:22,530 --> 00:03:23,940
in synapses.

59
00:03:23,940 --> 00:03:28,070
So in an action potential--

60
00:03:28,070 --> 00:03:30,930
and the sequence of
an action potential--

61
00:03:35,880 --> 00:03:41,160
we define three phases,
along the length of the axon

62
00:03:41,160 --> 00:03:43,290
with regard to the
membrane potential

63
00:03:43,290 --> 00:03:45,930
that was involved in
transmitting the signal,

64
00:03:45,930 --> 00:03:51,660
along the very long axon,
intracellular signaling those

65
00:03:51,660 --> 00:04:02,970
with arresting potential,
the threshold or the action

66
00:04:02,970 --> 00:04:06,270
potential of the threshold
leading to the action

67
00:04:06,270 --> 00:04:12,000
potential, and then the
question of repolarization,

68
00:04:12,000 --> 00:04:17,339
resetting the membrane
potential, which is pivotal.

69
00:04:17,339 --> 00:04:19,485
Otherwise, the cell
can't fire again.

70
00:04:22,630 --> 00:04:26,190
And we talked about one
pump, which is really pivotal

71
00:04:26,190 --> 00:04:29,120
for life-- we study it
in my own laboratory--

72
00:04:29,120 --> 00:04:32,130
but one pump which
is on all the time

73
00:04:32,130 --> 00:04:35,860
and which is involved primarily
in the resting potential

74
00:04:35,860 --> 00:04:37,660
and the repolarization.

75
00:04:37,660 --> 00:04:43,750
This is the sodium
potassium pump.

76
00:04:43,750 --> 00:04:50,610
It pumps sodium out and
potassium in, but less sodium

77
00:04:50,610 --> 00:04:52,520
out and potassium in.

78
00:04:52,520 --> 00:04:56,700
And it is on all the time.

79
00:04:56,700 --> 00:05:01,540
There are other channels
that are open all the time.

80
00:05:01,540 --> 00:05:06,540
The key one are
potassium channels,

81
00:05:06,540 --> 00:05:12,420
but there are also open
chloride and sodium channels.

82
00:05:12,420 --> 00:05:14,680
And those are open all the time.

83
00:05:14,680 --> 00:05:16,350
And depending on
the concentration

84
00:05:16,350 --> 00:05:21,000
of the ions, and also
electrostatic repulsion,

85
00:05:21,000 --> 00:05:25,650
which will counter sometimes
movement along a concentration

86
00:05:25,650 --> 00:05:29,460
gradient, those are
involved in everything.

87
00:05:29,460 --> 00:05:32,340
But primarily-- they're
open all the time--

88
00:05:32,340 --> 00:05:37,220
but they are primarily involved
in setting up resting potential

89
00:05:37,220 --> 00:05:39,120
and repolarization.

90
00:05:39,120 --> 00:05:41,670
So we'll put some dots.

91
00:05:41,670 --> 00:05:48,330
I'm going to dash the line
in the action potential area,

92
00:05:48,330 --> 00:05:51,570
which indicates that those
pumps and channel, that pump

93
00:05:51,570 --> 00:05:54,210
and channel are being
used and active,

94
00:05:54,210 --> 00:05:56,790
but they're not pivotal
in those processes.

95
00:05:56,790 --> 00:06:00,180
The one that's really pivotal
in the action potential

96
00:06:00,180 --> 00:06:03,150
is the voltage gated
sodium channel.

97
00:06:07,120 --> 00:06:08,710
We talked about this last time.

98
00:06:08,710 --> 00:06:11,020
You can look a bit
more on the slides

99
00:06:11,020 --> 00:06:14,740
that I posted with
regard to the ideas

100
00:06:14,740 --> 00:06:20,530
behind how the channel is closed
at certain membrane potential,

101
00:06:20,530 --> 00:06:23,470
how if the membrane
potential changes slightly,

102
00:06:23,470 --> 00:06:26,440
there's a conformational
change in the protein.

103
00:06:26,440 --> 00:06:29,140
And a pore opens
that allows sodium

104
00:06:29,140 --> 00:06:32,290
to rush in down its
concentration gradient,

105
00:06:32,290 --> 00:06:35,110
over a very small
area of membrane.

106
00:06:35,110 --> 00:06:40,840
So the voltage gated sodium
channel allows sodium in,

107
00:06:40,840 --> 00:06:45,320
and it is closed,
if we look at this.

108
00:06:45,320 --> 00:06:49,660
It's open during an
action potential.

109
00:06:49,660 --> 00:06:57,280
It is closed at resting,
but is ready to be open.

110
00:06:57,280 --> 00:07:04,510
And then subsequently, it is
closed during repolarization

111
00:07:04,510 --> 00:07:06,940
when the membrane
potential is reset.

112
00:07:06,940 --> 00:07:09,040
And it's not openable--

113
00:07:09,040 --> 00:07:12,970
it's not actually clear why--
there's some funny confirmation

114
00:07:12,970 --> 00:07:17,800
and that pump is not ready to be
opened for some period of time

115
00:07:17,800 --> 00:07:20,680
until the protein
structure resets itself.

116
00:07:20,680 --> 00:07:21,700
And then it's openable.

117
00:07:21,700 --> 00:07:26,800
So it's closed and it's
not ready to be opened.

118
00:07:26,800 --> 00:07:30,100
And this is really
pivotal in making sure

119
00:07:30,100 --> 00:07:32,200
that an action
potential traverses

120
00:07:32,200 --> 00:07:36,160
in one direction along the
axon, and doesn't go backwards

121
00:07:36,160 --> 00:07:38,590
as the ions diffuse backwards.

122
00:07:38,590 --> 00:07:40,760
And then finally,
I want to mention--

123
00:07:40,760 --> 00:07:42,520
or I want to tell you--

124
00:07:42,520 --> 00:07:49,930
that there is a voltage gated
potassium channel that opens up

125
00:07:49,930 --> 00:07:52,610
after the action potential.

126
00:07:52,610 --> 00:07:54,220
And that is one
of the things that

127
00:07:54,220 --> 00:07:57,130
is pivotal in resetting
the membrane potential

128
00:07:57,130 --> 00:07:59,020
during repolarization.

129
00:07:59,020 --> 00:08:01,390
The other thing that
is really pivotal

130
00:08:01,390 --> 00:08:04,220
is this sodium potassium pump.

131
00:08:04,220 --> 00:08:08,530
So the voltage gated
potassium channel

132
00:08:08,530 --> 00:08:14,160
gets potassium out of
the cell in the area

133
00:08:14,160 --> 00:08:16,380
where there has
been depolarization.

134
00:08:16,380 --> 00:08:19,530
Your very positive
inside ions go out

135
00:08:19,530 --> 00:08:21,630
along their
concentration gradient,

136
00:08:21,630 --> 00:08:24,600
or along an
electrostatic gradient.

137
00:08:24,600 --> 00:08:28,920
And so potassium goes
out, both in this case.

138
00:08:28,920 --> 00:08:33,299
And so it is open
during repolarization,

139
00:08:33,299 --> 00:08:37,110
and it is closed for
the rest of the time.

140
00:08:43,669 --> 00:08:44,836
OK.

141
00:08:44,836 --> 00:08:47,210
The thing you're going to have
to do with these channels,

142
00:08:47,210 --> 00:08:49,530
that you will do in section
and with your problem set,

143
00:08:49,530 --> 00:08:51,940
is to really work
through the kind of logic

144
00:08:51,940 --> 00:08:55,390
behind what pump and channel
is doing what at what

145
00:08:55,390 --> 00:08:58,280
stage of the action potential.

146
00:08:58,280 --> 00:09:00,110
And then it will
start to make sense.

147
00:09:00,110 --> 00:09:00,610
OK.

148
00:09:06,659 --> 00:09:08,200
So we're going to
move on in a moment

149
00:09:08,200 --> 00:09:09,460
and talk about the synapse.

150
00:09:09,460 --> 00:09:12,970
But I'm going to talk about
the pumps and channels

151
00:09:12,970 --> 00:09:18,760
during a synapse, and point
out to you that these pumps

152
00:09:18,760 --> 00:09:22,840
and channels are being
used, but there are others,

153
00:09:22,840 --> 00:09:24,770
which are really crucial.

154
00:09:24,770 --> 00:09:27,500
One of them is the
voltage gated--

155
00:09:27,500 --> 00:09:30,760
VG for voltage gated--

156
00:09:30,760 --> 00:09:31,610
calcium channel.

157
00:09:35,150 --> 00:09:43,570
And the other are a
series of ligand gated,

158
00:09:43,570 --> 00:09:45,560
or second messenger gated.

159
00:09:50,740 --> 00:09:57,390
Second messenger regulated,
let's say, not gated, ion

160
00:09:57,390 --> 00:09:57,890
channels.

161
00:10:04,550 --> 00:10:09,710
And these ligand gated, or
voltage gated second messenger

162
00:10:09,710 --> 00:10:14,540
regulated channels, these things
are specific to the synapse,

163
00:10:14,540 --> 00:10:17,345
and are specific to the
connections between cells.

164
00:10:33,120 --> 00:10:36,170
So let's move on
to the major topic

165
00:10:36,170 --> 00:10:42,760
today, which is this question
of the synapse, the connection

166
00:10:42,760 --> 00:10:43,660
between cells.

167
00:10:49,560 --> 00:10:50,940
And let me throw out some facts.

168
00:10:50,940 --> 00:10:52,856
And then I'll show you
kind of a cool picture.

169
00:10:55,320 --> 00:10:58,230
Neurons connect with one
another to make circuits.

170
00:10:58,230 --> 00:10:59,140
That's the deal.

171
00:10:59,140 --> 00:11:00,420
That's the wiring.

172
00:11:00,420 --> 00:11:02,340
So how complex is this wiring?

173
00:11:02,340 --> 00:11:04,770
I showed you a very
cool 3D reconstruction

174
00:11:04,770 --> 00:11:07,590
of the brain that
showed you the packing

175
00:11:07,590 --> 00:11:09,510
of the neurons in the brain.

176
00:11:09,510 --> 00:11:12,360
But quantitatively,
what does that mean?

177
00:11:12,360 --> 00:11:20,010
One neuron can connect with,
can synapse with up to 100,000

178
00:11:20,010 --> 00:11:20,625
other neurons.

179
00:11:31,890 --> 00:11:35,830
In the brain alone, there are
at least 10 to the 10th neurons.

180
00:11:49,610 --> 00:11:51,450
It's not clear
really, to anyone,

181
00:11:51,450 --> 00:11:53,420
how you put those
two numbers together,

182
00:11:53,420 --> 00:11:57,790
whether you can multiply
them, and whether that's fair.

183
00:11:57,790 --> 00:11:59,920
But whatever you
come out with, that's

184
00:11:59,920 --> 00:12:02,950
a lot of connections,
just in the brain.

185
00:12:02,950 --> 00:12:05,140
OK?

186
00:12:05,140 --> 00:12:09,320
The number of synapses,
therefore, is huge.

187
00:12:09,320 --> 00:12:11,650
So what kinds of
connections are there?

188
00:12:11,650 --> 00:12:13,399
Let's just write this.

189
00:12:13,399 --> 00:12:14,440
I'm not going to try to--

190
00:12:17,200 --> 00:12:19,419
huge number of synapses.

191
00:12:19,419 --> 00:12:19,960
There you go.

192
00:12:19,960 --> 00:12:20,970
That's quantitative.

193
00:12:23,560 --> 00:12:25,450
What are these connections?

194
00:12:25,450 --> 00:12:28,300
We've talked a lot about an
electrical signal moving down

195
00:12:28,300 --> 00:12:29,590
the axon.

196
00:12:29,590 --> 00:12:31,840
But now I'm going to
tell you that most

197
00:12:31,840 --> 00:12:34,890
connections between
cells are not electrical,

198
00:12:34,890 --> 00:12:36,190
they're chemical.

199
00:12:36,190 --> 00:12:39,520
And I told you last time
when we explored the reason

200
00:12:39,520 --> 00:12:42,730
that you have these long
axons and intracellular

201
00:12:42,730 --> 00:12:45,970
signaling rather than cells
all piled up next to one

202
00:12:45,970 --> 00:12:50,200
another doing intracellular
signaling, that's slow.

203
00:12:50,200 --> 00:12:51,550
I told you that last time.

204
00:12:51,550 --> 00:12:53,830
And that's still
true in a synapse.

205
00:12:53,830 --> 00:12:56,260
The connections
between the cells

206
00:12:56,260 --> 00:13:00,790
is the slow point of
neural transmission.

207
00:13:00,790 --> 00:13:02,425
There are electrical synapses.

208
00:13:07,060 --> 00:13:10,660
And they are used
sometimes, but rarely.

209
00:13:10,660 --> 00:13:17,980
They are fact because they are
connected by gap junctions, one

210
00:13:17,980 --> 00:13:20,320
neuron to another.

211
00:13:20,320 --> 00:13:23,710
And that allows ion flow.

212
00:13:28,130 --> 00:13:32,260
But the thing about
electrical synapses

213
00:13:32,260 --> 00:13:33,620
is that they're always open.

214
00:13:33,620 --> 00:13:35,510
The cells are always connected.

215
00:13:35,510 --> 00:13:36,740
They're unregulated.

216
00:13:43,260 --> 00:13:45,630
And the thing about
the nervous system

217
00:13:45,630 --> 00:13:48,450
is that it is
exquisitely regulated.

218
00:13:48,450 --> 00:13:52,140
It is fine-tuned to respond
to the smallest stimuli,

219
00:13:52,140 --> 00:13:55,260
both from within your
body and from without.

220
00:13:55,260 --> 00:13:58,590
And unregulated synapses
will not do that for you.

221
00:13:58,590 --> 00:14:01,625
So the flip of those
are chemicals synapses.

222
00:14:07,310 --> 00:14:19,390
They are slow, their
diffusion limited,

223
00:14:19,390 --> 00:14:23,310
and they're diffusion
limited of chemicals

224
00:14:23,310 --> 00:14:25,920
that we'll discuss
in detail, that

225
00:14:25,920 --> 00:14:27,700
are called neurotransmitters.

226
00:14:38,830 --> 00:14:41,500
But they have the
wonderful property

227
00:14:41,500 --> 00:14:43,940
of being highly regulatable.

228
00:14:49,160 --> 00:14:55,390
And so the majority of
synapses in higher animals

229
00:14:55,390 --> 00:14:57,430
are these chemical synapses.

230
00:14:57,430 --> 00:14:59,110
And that's what we'll
talk about today.

231
00:15:04,830 --> 00:15:06,550
This is a picture
which I really like.

232
00:15:06,550 --> 00:15:08,780
It's a neuron where--

233
00:15:08,780 --> 00:15:10,070
and these are the dendrites.

234
00:15:10,070 --> 00:15:12,920
And here's the cell body
and the axon coming out.

235
00:15:12,920 --> 00:15:15,410
And each of these dots
represents a synapse.

236
00:15:15,410 --> 00:15:17,000
Well, it doesn't
represent a synapse.

237
00:15:17,000 --> 00:15:19,430
It is, it's stained
for a protein that's

238
00:15:19,430 --> 00:15:21,170
only found in synapses.

239
00:15:21,170 --> 00:15:24,710
And you can see this tremendous
studding of the dendrites

240
00:15:24,710 --> 00:15:28,040
with synapses, which gives
you a sense of the complexity.

241
00:15:31,420 --> 00:15:31,920
OK.

242
00:15:35,320 --> 00:15:37,950
It's really pivotal, when we
talk about the connections,

243
00:15:37,950 --> 00:15:40,160
that we get some of
the principles correct.

244
00:15:40,160 --> 00:15:43,600
So I want to spend a board going
through some of the principles

245
00:15:43,600 --> 00:15:46,580
that we have to bear in mind in
thinking about the connections.

246
00:15:52,250 --> 00:15:53,580
So let's think about this.

247
00:15:53,580 --> 00:16:01,890
Here are neurons-- well,
let's have Neuron 1.

248
00:16:01,890 --> 00:16:04,240
But we could actually
have Neuron 1 to n.

249
00:16:04,240 --> 00:16:05,050
It doesn't matter.

250
00:16:05,050 --> 00:16:07,310
It could be a whole
bunch of Neuron 1.

251
00:16:07,310 --> 00:16:10,320
And along that one neuron,
or those bunches of neurons,

252
00:16:10,320 --> 00:16:12,050
is coming an action potential.

253
00:16:17,370 --> 00:16:20,470
And over here is Neuron 2.

254
00:16:25,230 --> 00:16:29,640
And between them is a
connection, is a synapse.

255
00:16:32,640 --> 00:16:35,610
And the thing that Neuron 2
has to decide when it connects

256
00:16:35,610 --> 00:16:37,920
with Neuron 1 is
whether it's going

257
00:16:37,920 --> 00:16:40,380
to make an action
potential, whether it's

258
00:16:40,380 --> 00:16:43,070
going to send a signal.

259
00:16:43,070 --> 00:16:46,640
That is the big decision
that this neuron has to make.

260
00:16:46,640 --> 00:16:56,470
So Neuron 2 must decide to
make an action potential,

261
00:16:56,470 --> 00:16:58,830
and it is a yes/no decision.

262
00:16:58,830 --> 00:17:01,140
It's not a sort of
an action potential

263
00:17:01,140 --> 00:17:03,790
or a half an action potential.

264
00:17:03,790 --> 00:17:11,490
And so we need to remember
action potential facts, all

265
00:17:11,490 --> 00:17:12,359
or none.

266
00:17:12,359 --> 00:17:15,780
You either get an action
potential or you don't.

267
00:17:15,780 --> 00:17:18,990
That means you get complete
depolarization or nothing.

268
00:17:25,760 --> 00:17:30,630
And if you have a lot of action
potentials coming along Neuron

269
00:17:30,630 --> 00:17:33,770
1, the way Neuron 2
can respond is not

270
00:17:33,770 --> 00:17:36,230
to make a big action
potential, obviously.

271
00:17:36,230 --> 00:17:38,940
But it can make a lot
of action potentials.

272
00:17:38,940 --> 00:17:48,760
So a change in input where we
can call this action potential

273
00:17:48,760 --> 00:17:51,520
from Neuron 1, the
input, a change

274
00:17:51,520 --> 00:17:57,440
in input results in
an increase or change,

275
00:17:57,440 --> 00:18:01,540
let's just say, a
change in the number

276
00:18:01,540 --> 00:18:08,380
of action potentials per time,
or the frequency of action

277
00:18:08,380 --> 00:18:13,780
potentials in Neuron 2.

278
00:18:18,060 --> 00:18:22,015
Other facts, other
really key facts.

279
00:18:25,310 --> 00:18:27,075
Resting potential can change.

280
00:18:36,920 --> 00:18:39,620
Threshold potential and
the action potential,

281
00:18:39,620 --> 00:18:41,705
as I've been belaboring,
do not change.

282
00:18:56,510 --> 00:19:01,170
And you can see that nicely
in the slide, where here's

283
00:19:01,170 --> 00:19:03,540
a neuron firing, and
this is a different way

284
00:19:03,540 --> 00:19:06,170
of showing the neuron firing.

285
00:19:06,170 --> 00:19:08,250
Here is the action
potential showing

286
00:19:08,250 --> 00:19:11,880
as a spike of depolarization.

287
00:19:11,880 --> 00:19:14,890
And then there's a
time, another spike,

288
00:19:14,890 --> 00:19:19,240
another action potential,
wait, another spike, and so on.

289
00:19:19,240 --> 00:19:22,376
Here is a neuron that's
gotten a lot of input.

290
00:19:22,376 --> 00:19:23,000
And look at it.

291
00:19:23,000 --> 00:19:25,020
It's spike, spike,
spike, spike, spike.

292
00:19:25,020 --> 00:19:27,330
But if you look at the
height of that spike,

293
00:19:27,330 --> 00:19:29,730
that is the
depolarization height.

294
00:19:29,730 --> 00:19:32,520
It's the same within
the sensitivity

295
00:19:32,520 --> 00:19:36,490
of the recording device for
each of these action potentials.

296
00:19:36,490 --> 00:19:41,010
So I really like that slide
to exemplify these principles

297
00:19:41,010 --> 00:19:43,480
that I've just
put on this board.

298
00:19:43,480 --> 00:19:43,980
OK.

299
00:19:46,770 --> 00:19:47,880
There are the principles.

300
00:19:47,880 --> 00:19:49,230
How does it work?

301
00:19:49,230 --> 00:19:50,130
Very cool.

302
00:19:50,130 --> 00:19:52,710
This is really amazing.

303
00:19:52,710 --> 00:19:56,750
Let's again have Axon 1.

304
00:19:56,750 --> 00:19:58,281
We're going to have Axon 1 here.

305
00:19:58,281 --> 00:19:58,780
OK?

306
00:19:58,780 --> 00:20:03,440
Axon, oh, let's have axon
derived from Neuron 1.

307
00:20:06,750 --> 00:20:09,240
And now we've got to
distinguish two different parts

308
00:20:09,240 --> 00:20:09,775
of the axon.

309
00:20:14,316 --> 00:20:15,940
And I'm going to draw
this on the board

310
00:20:15,940 --> 00:20:18,398
and then I'm going to go through
it with you on a hand out,

311
00:20:18,398 --> 00:20:19,990
because it's important.

312
00:20:19,990 --> 00:20:22,960
There's an electrical
signal coming along Axon 1.

313
00:20:26,280 --> 00:20:29,200
And you know that it
involves an action

314
00:20:29,200 --> 00:20:33,010
potential via the voltage
gated sodium channels.

315
00:20:38,920 --> 00:20:42,820
As that signal nears
the end of the axon,

316
00:20:42,820 --> 00:20:46,630
the axon kind of bulges
out into a terminal,

317
00:20:46,630 --> 00:20:50,845
and the voltage gated channels
change from sodium to calcium.

318
00:20:53,650 --> 00:20:56,470
So here's the end of the axon.

319
00:20:56,470 --> 00:21:02,170
And here you change to
voltage gated calcium

320
00:21:02,170 --> 00:21:07,911
channels that are activated.

321
00:21:07,911 --> 00:21:08,410
OK.

322
00:21:11,070 --> 00:21:13,890
These voltage gated
calcium channels,

323
00:21:13,890 --> 00:21:16,260
this is called-- actually,
let's put some terminology.

324
00:21:16,260 --> 00:21:22,040
This is called the
pre-synaptic neuron.

325
00:21:22,040 --> 00:21:24,510
And the voltage gated
calcium channels are

326
00:21:24,510 --> 00:21:26,455
at the pre-synaptic terminus.

327
00:21:34,360 --> 00:21:38,200
Now the thing about calcium
that we've mentioned

328
00:21:38,200 --> 00:21:43,420
before is that it is a
mediator of exocytosis,

329
00:21:43,420 --> 00:21:45,910
of having little
vesicles containing

330
00:21:45,910 --> 00:21:49,660
proteins or other molecules
released from the cell.

331
00:21:49,660 --> 00:21:54,820
These voltage gated calcium
channels increase intracellular

332
00:21:54,820 --> 00:22:05,630
calcium and lead
to the exocytosis,

333
00:22:05,630 --> 00:22:08,840
the release of
chemicals that are

334
00:22:08,840 --> 00:22:11,870
contained in
vesicles at the end,

335
00:22:11,870 --> 00:22:14,210
at the pre-synaptic terminus.

336
00:22:14,210 --> 00:22:21,850
So the pre-synaptic
terminus contains vesicles

337
00:22:21,850 --> 00:22:24,500
with neurotransmitter.

338
00:22:24,500 --> 00:22:26,030
We'll talk about this in detail.

339
00:22:30,150 --> 00:22:33,050
The voltage gated
calcium channels,

340
00:22:33,050 --> 00:22:37,120
which increase
intracellular calcium,

341
00:22:37,120 --> 00:22:46,810
lead to exocytosis release of
the neurotransmitter, which

342
00:22:46,810 --> 00:22:50,480
is released outside the cell.

343
00:22:50,480 --> 00:22:54,890
And that neurotransmitter
diffuses across the space

344
00:22:54,890 --> 00:22:58,982
between Neuron 1 and Neuron 2.

345
00:22:58,982 --> 00:23:00,850
It's about 30 nanometers.

346
00:23:00,850 --> 00:23:03,230
And it diffuses
across the space.

347
00:23:03,230 --> 00:23:07,760
And when it gets to
the other side to--

348
00:23:07,760 --> 00:23:13,010
here's Neuron 2, called
the post-synaptic neuron--

349
00:23:18,250 --> 00:23:21,250
when it gets to the
other side, and it'll

350
00:23:21,250 --> 00:23:33,850
get to either the
dendrites or the cell body,

351
00:23:33,850 --> 00:23:40,350
this neurotransmitter
binds to things

352
00:23:40,350 --> 00:23:44,980
that we've talked about a
lot, it binds to receptors.

353
00:23:44,980 --> 00:23:48,160
Those receptors plus
ligand do all the things

354
00:23:48,160 --> 00:23:50,650
we've talked about
in many lectures.

355
00:23:50,650 --> 00:23:52,810
They do something.

356
00:23:52,810 --> 00:23:54,820
In this case, they can
do one of two things,

357
00:23:54,820 --> 00:23:56,230
as we'll talk about.

358
00:23:56,230 --> 00:24:00,430
But it all culminates
in changing ion flux

359
00:24:00,430 --> 00:24:03,250
across the
post-synaptic membrane.

360
00:24:03,250 --> 00:24:06,760
So the neurotransmitter
diffuses.

361
00:24:06,760 --> 00:24:09,790
It hits the dendrites,
or cell body.

362
00:24:09,790 --> 00:24:22,710
It binds receptors to change
ion flux, or ion movement.

363
00:24:25,420 --> 00:24:31,900
And this eventually gets
turned into the action

364
00:24:31,900 --> 00:24:32,875
potential decision.

365
00:24:37,980 --> 00:24:39,180
OK.

366
00:24:39,180 --> 00:24:42,000
So let's put some more on here.

367
00:24:42,000 --> 00:24:47,840
Here's an electrical
signal from Neuron 1.

368
00:24:47,840 --> 00:24:51,150
Here, this
neurotransmitter diffusion

369
00:24:51,150 --> 00:24:58,780
is a chemical signal
across what is

370
00:24:58,780 --> 00:25:06,490
called the synaptic cleft, which
is the space between neurons.

371
00:25:06,490 --> 00:25:14,050
And the signal in Neuron 2
becomes electrical again.

372
00:25:14,050 --> 00:25:17,350
So there's a conversion
device, which

373
00:25:17,350 --> 00:25:21,530
converts electrical to
chemical to electrical signals.

374
00:25:21,530 --> 00:25:22,030
All right.

375
00:25:22,030 --> 00:25:24,910
Let's look at your
first handout and we'll

376
00:25:24,910 --> 00:25:26,230
hammer this in in more detail.

377
00:25:31,030 --> 00:25:33,780
Here's the action potential.

378
00:25:33,780 --> 00:25:36,154
So let me stand here
in case you're--

379
00:25:36,154 --> 00:25:37,320
they don't like me doing it.

380
00:25:37,320 --> 00:25:37,820
OK.

381
00:25:37,820 --> 00:25:38,910
Let me stand here.

382
00:25:38,910 --> 00:25:43,800
Here's the action potential
coming along Neuron 1.

383
00:25:43,800 --> 00:25:46,230
Voltage gated sodium
channels until you

384
00:25:46,230 --> 00:25:48,510
get near the end,
when you switch

385
00:25:48,510 --> 00:25:51,420
to these voltage gated
calcium channels.

386
00:25:51,420 --> 00:25:58,290
Calcium flows in, leads
to exocytosis of vesicles

387
00:25:58,290 --> 00:26:00,410
containing neurotransmitter.

388
00:26:00,410 --> 00:26:04,470
The neurotransmitter diffuses
across the synaptic cleft,

389
00:26:04,470 --> 00:26:09,570
binds to receptors on either
side, which changes the ion

390
00:26:09,570 --> 00:26:13,950
flux into Neuron 2.

391
00:26:13,950 --> 00:26:18,030
And there is an action
potential decision--

392
00:26:18,030 --> 00:26:19,290
it's on your sheet--

393
00:26:19,290 --> 00:26:22,440
an action potential
decision that eventually,

394
00:26:22,440 --> 00:26:26,370
as we'll discuss, involves
voltage gated sodium channels

395
00:26:26,370 --> 00:26:29,850
so that the cell
decides whether or not

396
00:26:29,850 --> 00:26:32,660
it's going to fire
an action potential.

397
00:26:32,660 --> 00:26:33,160
OK.

398
00:26:33,160 --> 00:26:36,270
We'll talk about the
neurotransmitters

399
00:26:36,270 --> 00:26:39,070
and the receptors in
more detail in a moment.

400
00:26:39,070 --> 00:26:43,980
But I want to introduce
you to three concepts

401
00:26:43,980 --> 00:26:47,800
of the synapse, which are
really very important.

402
00:26:47,800 --> 00:26:50,160
The first is the
concept of summation.

403
00:26:54,220 --> 00:26:58,290
And now we go back to the
notion that many neurons

404
00:26:58,290 --> 00:27:02,640
can give signals to
another neuron, such

405
00:27:02,640 --> 00:27:05,340
that that other neuron
is deciding yes, no, I'm

406
00:27:05,340 --> 00:27:07,020
going to fire an
action potential

407
00:27:07,020 --> 00:27:09,290
and transmit the signal.

408
00:27:09,290 --> 00:27:12,720
The neuron that's receiving
all of that signaling

409
00:27:12,720 --> 00:27:18,030
has to add up its inputs and say
what's the sum of the inputs.

410
00:27:18,030 --> 00:27:20,560
Literally, it has to
add up the inputs.

411
00:27:20,560 --> 00:27:34,620
So summation is the addition
of all synaptic input, which

412
00:27:34,620 --> 00:27:46,230
is change in membrane potential
governed by change in ion

413
00:27:46,230 --> 00:27:54,435
movement on a recipient neuron.

414
00:27:59,410 --> 00:28:00,650
OK.

415
00:28:00,650 --> 00:28:03,380
So the addition of
all synaptic input

416
00:28:03,380 --> 00:28:05,960
on a recipient neuron,
or bio-recipient neuron,

417
00:28:05,960 --> 00:28:07,400
if you like.

418
00:28:07,400 --> 00:28:08,910
There's two kinds.

419
00:28:08,910 --> 00:28:14,630
There's spatial
summation, which has to do

420
00:28:14,630 --> 00:28:16,110
where the signal is received.

421
00:28:23,020 --> 00:28:26,290
And so those synapses
that I showed you

422
00:28:26,290 --> 00:28:29,590
in that picture of the
cell with all its dendrites

423
00:28:29,590 --> 00:28:32,650
and all of those little dots
were all over the place?

424
00:28:32,650 --> 00:28:34,540
Each of those little
dots is getting

425
00:28:34,540 --> 00:28:38,320
a signal on the
dendrites, on the ends

426
00:28:38,320 --> 00:28:41,410
of the dendrites, near the
cell body, in the cell body.

427
00:28:41,410 --> 00:28:44,520
All of those inputs
have to be added up.

428
00:28:44,520 --> 00:28:47,040
So where the signal
received, is received,

429
00:28:47,040 --> 00:28:57,140
cell body plus dendrites, that
would be spatial summation.

430
00:28:57,140 --> 00:29:02,040
And then temporal
summation means over time,

431
00:29:02,040 --> 00:29:03,510
when the signal is received.

432
00:29:07,880 --> 00:29:11,600
Over a period of a
millisecond or so,

433
00:29:11,600 --> 00:29:15,770
all of those inputs to
the neuron are added up.

434
00:29:15,770 --> 00:29:18,510
And the addition is
actually a simple one.

435
00:29:18,510 --> 00:29:23,540
The addition is how much has
the membrane potential changed,

436
00:29:23,540 --> 00:29:26,510
and overall, have you brought
the membrane potential

437
00:29:26,510 --> 00:29:29,930
of the recipient
neuron up to threshold.

438
00:29:29,930 --> 00:29:33,080
If you have, that
recipient neuron fires.

439
00:29:33,080 --> 00:29:35,390
And if you haven't, it doesn't.

440
00:29:35,390 --> 00:29:37,770
So the total
membrane potential--

441
00:29:37,770 --> 00:29:43,820
so the answer of
whether to fire or not,

442
00:29:43,820 --> 00:29:59,200
is the total membrane potential,
which is the decision.

443
00:29:59,200 --> 00:30:06,090
And if it's threshold
potential, out of that,

444
00:30:06,090 --> 00:30:09,035
an action potential results.

445
00:30:12,260 --> 00:30:16,310
The addition, the summation
is done in the dendrites

446
00:30:16,310 --> 00:30:17,750
and the cell body.

447
00:30:17,750 --> 00:30:22,400
And the answer is read at the
place where the axon comes off

448
00:30:22,400 --> 00:30:26,930
the cell body, which is
called the axon hillock.

449
00:30:26,930 --> 00:30:39,340
So the sum is calculated
over all of the dendrites

450
00:30:39,340 --> 00:30:42,710
plus the cell body.

451
00:30:42,710 --> 00:30:48,290
But it is read at this thing
called the axon hillock.

452
00:30:51,340 --> 00:30:58,660
And they only read
the axon hillock

453
00:30:58,660 --> 00:31:02,860
is where the axon
leaves the cell body,

454
00:31:02,860 --> 00:31:04,705
or originates from
the cell body.

455
00:31:07,660 --> 00:31:12,510
And the reason that that
is an important place

456
00:31:12,510 --> 00:31:15,300
is that that is where
the voltage gated

457
00:31:15,300 --> 00:31:18,150
sodium channels are found.

458
00:31:18,150 --> 00:31:19,320
It's only there.

459
00:31:19,320 --> 00:31:22,560
They start at the axon
hillock, and they are present

460
00:31:22,560 --> 00:31:23,917
all the way down the axon.

461
00:31:23,917 --> 00:31:25,875
There are no-- and you
can look at your diagram

462
00:31:25,875 --> 00:31:28,620
for this-- there are
no voltage gated sodium

463
00:31:28,620 --> 00:31:31,800
channels in the cell
body or the dendrites.

464
00:31:31,800 --> 00:31:34,410
So they can't fire
an action potential.

465
00:31:34,410 --> 00:31:37,470
They can add up how
membrane potentials changed,

466
00:31:37,470 --> 00:31:39,760
but they can't do
anything about it.

467
00:31:39,760 --> 00:31:43,530
So the hillock is where the
axon leaves the cell body,

468
00:31:43,530 --> 00:32:01,580
and where the voltage gated
sodium channels begin, begin,

469
00:32:01,580 --> 00:32:05,240
and where an action potential
can therefore come out.

470
00:32:05,240 --> 00:32:08,962
That's a bunch of sentences.

471
00:32:08,962 --> 00:32:09,462
OK.

472
00:32:13,250 --> 00:32:15,280
Couple more terms.

473
00:32:15,280 --> 00:32:18,400
Excitatory and
inhibitory synapses,

474
00:32:18,400 --> 00:32:21,790
excitatory and inhibitory.

475
00:32:38,800 --> 00:32:42,320
It's kind of like a
simple math problem

476
00:32:42,320 --> 00:32:45,440
where you're adding positive
numbers or negative numbers.

477
00:32:45,440 --> 00:32:48,140
You know, you come out with
something that's either 0,

478
00:32:48,140 --> 00:32:50,000
negative, or positive.

479
00:32:50,000 --> 00:32:51,680
Same idea here.

480
00:32:51,680 --> 00:32:55,430
When you add all these
inputs that a neuron gets,

481
00:32:55,430 --> 00:32:57,830
it figures out what
it's going to do.

482
00:32:57,830 --> 00:33:01,670
And the inputs can be either
pushing a neuron closer

483
00:33:01,670 --> 00:33:05,120
towards an action potential,
closer towards threshold,

484
00:33:05,120 --> 00:33:07,580
or pushing a neuron
away from being

485
00:33:07,580 --> 00:33:10,160
able to make an action
potential, further

486
00:33:10,160 --> 00:33:11,900
away from threshold.

487
00:33:11,900 --> 00:33:19,070
Excitatory synapses bring
the resting potential

488
00:33:19,070 --> 00:33:34,320
closer to threshold,
whereas inhibitory

489
00:33:34,320 --> 00:33:39,890
bring the resting potential
further from threshold.

490
00:33:47,390 --> 00:33:47,890
All right.

491
00:33:47,890 --> 00:33:50,920
Here's where it gets
even more complicated.

492
00:33:50,920 --> 00:33:55,030
One neuron can be making both
excitatory and inhibitory

493
00:33:55,030 --> 00:33:56,210
synapses.

494
00:33:56,210 --> 00:33:58,720
And depending on
which predominate,

495
00:33:58,720 --> 00:34:00,310
the recipient neuron
will either be

496
00:34:00,310 --> 00:34:03,070
told to fire or not
to fire, to make

497
00:34:03,070 --> 00:34:05,660
an action potential or not.

498
00:34:05,660 --> 00:34:22,316
So one neuron can make both
excitatory and inhibitory

499
00:34:22,316 --> 00:34:22,816
synapses.

500
00:34:25,420 --> 00:34:27,330
How does this work, you ask?

501
00:34:27,330 --> 00:34:30,190
Well, you have all
the tools to know.

502
00:34:30,190 --> 00:34:34,929
It's all got to do with ion flux
and which ions are flowing in

503
00:34:34,929 --> 00:34:37,480
and which ions are flowing out.

504
00:34:37,480 --> 00:34:40,270
And we can answer that by
looking at your next handouts.

505
00:34:45,590 --> 00:34:47,790
In Number 2 of
your handouts, I've

506
00:34:47,790 --> 00:34:49,500
shown you the synaptic cleft.

507
00:34:49,500 --> 00:34:51,330
Here's a synaptic cleft.

508
00:34:51,330 --> 00:34:53,850
And here are the voltage
gated calcium channels

509
00:34:53,850 --> 00:34:57,960
opening to allow calcium
in and neurotransmitter

510
00:34:57,960 --> 00:34:59,580
vesicle exocytosis.

511
00:35:03,050 --> 00:35:07,360
Here is an excitatory synapse
bringing the resting potential

512
00:35:07,360 --> 00:35:09,130
closer to threshold.

513
00:35:09,130 --> 00:35:10,960
Let's think about that.

514
00:35:10,960 --> 00:35:15,340
You want positive ions to
come in from the outside.

515
00:35:15,340 --> 00:35:17,980
That would help bring
your resting potential

516
00:35:17,980 --> 00:35:19,820
closer to threshold.

517
00:35:19,820 --> 00:35:22,780
So there is some sodium
channels that can open,

518
00:35:22,780 --> 00:35:25,870
maybe calcium channels that can
open-- not the voltage gated

519
00:35:25,870 --> 00:35:27,360
ones.

520
00:35:27,360 --> 00:35:29,860
And that would increase
the resting potential.

521
00:35:29,860 --> 00:35:32,700
That would increase the
potential inside the cell,

522
00:35:32,700 --> 00:35:36,520
bring it more positive,
closer to threshold.

523
00:35:36,520 --> 00:35:41,480
Conversely, in an
inhibitory synapse,

524
00:35:41,480 --> 00:35:44,390
you'd get a net inflow
of negative charges.

525
00:35:44,390 --> 00:35:48,260
The chloride ions might
move from the outside in.

526
00:35:48,260 --> 00:35:50,660
That would take, make
your inside of your cell

527
00:35:50,660 --> 00:35:54,170
more negative and further
away from threshold.

528
00:35:54,170 --> 00:35:56,360
You could also
get potassium out.

529
00:35:56,360 --> 00:35:58,550
And that would, again,
make the inside of the cell

530
00:35:58,550 --> 00:36:01,250
more negative and
further from threshold.

531
00:36:01,250 --> 00:36:04,032
So you can see already I've
got four different channels--

532
00:36:04,032 --> 00:36:05,990
they're not the ones
we've talked about before,

533
00:36:05,990 --> 00:36:07,100
they're different ones--

534
00:36:07,100 --> 00:36:09,170
four different
channels which can

535
00:36:09,170 --> 00:36:13,270
modulate the membrane potential
on the recipient cell.

536
00:36:16,330 --> 00:36:18,400
All right.

537
00:36:18,400 --> 00:36:26,200
Let us move on now to
those neurotransmitters

538
00:36:26,200 --> 00:36:27,652
and their receptors.

539
00:36:39,696 --> 00:36:43,890
Neurotransmitters and
neurotransmitter receptors

540
00:36:43,890 --> 00:36:46,050
are very cool because
they are probably

541
00:36:46,050 --> 00:36:50,310
what makes us who we are
in terms of personality,

542
00:36:50,310 --> 00:36:55,260
in terms of ability, in terms
of our interface with the world,

543
00:36:55,260 --> 00:36:59,070
in terms of whether we're an
intrinsically happy or not so

544
00:36:59,070 --> 00:37:01,980
happy person, er cetera.

545
00:37:01,980 --> 00:37:06,360
Neurotransmitters, however,
are a class of molecule

546
00:37:06,360 --> 00:37:08,760
we have previously encountered.

547
00:37:08,760 --> 00:37:12,960
They are ligands, but
they're different ligands.

548
00:37:12,960 --> 00:37:15,270
When we talked about
ligands previously,

549
00:37:15,270 --> 00:37:16,830
we have largely been talking--

550
00:37:16,830 --> 00:37:18,750
not entirely--
we've largely been

551
00:37:18,750 --> 00:37:24,780
talking about peptides
or molecules that

552
00:37:24,780 --> 00:37:26,820
are sort of a reasonable size.

553
00:37:26,820 --> 00:37:27,540
Not always.

554
00:37:27,540 --> 00:37:30,660
The steroid, the steroid
hormones are very tiny.

555
00:37:30,660 --> 00:37:35,310
Neurotransmitters are
pretty much all very tiny.

556
00:37:35,310 --> 00:37:36,960
And the thing that
you should know

557
00:37:36,960 --> 00:37:44,920
is that you can have one or
many types of neurotransmitter

558
00:37:44,920 --> 00:37:47,380
per synapse.

559
00:37:47,380 --> 00:37:48,860
Here's another complication.

560
00:37:55,770 --> 00:38:01,170
Neurotransmitters can
be peptides sometimes,

561
00:38:01,170 --> 00:38:05,280
but they are very largely amino
acids, the same amino acids

562
00:38:05,280 --> 00:38:11,160
that you build proteins
with, nucleotides,

563
00:38:11,160 --> 00:38:22,790
or other small molecules,
like the kinds of synapses.

564
00:38:22,790 --> 00:38:25,160
Synapses are excitatory
or inhibitory

565
00:38:25,160 --> 00:38:27,170
because of the kinds
of neurotransmitters

566
00:38:27,170 --> 00:38:28,620
that they're making.

567
00:38:28,620 --> 00:38:32,720
So there are excitatory
neurotransmitters.

568
00:38:35,330 --> 00:38:41,610
Glutamate, glutamate,
glutamate, glutamic acid--

569
00:38:41,610 --> 00:38:44,490
OK, the same one we've
talked about before--

570
00:38:44,490 --> 00:38:50,060
and adenine are both
examples of excitatory,

571
00:38:50,060 --> 00:38:56,360
are examples of excitatory
neurotransmitters.

572
00:38:56,360 --> 00:38:58,510
Glutamate is involved
in being alert.

573
00:39:06,160 --> 00:39:09,670
Adenine is involved
in being sleepy.

574
00:39:09,670 --> 00:39:12,130
And one of the things
that caffeine does

575
00:39:12,130 --> 00:39:15,220
is to counteract the
effects of adenine

576
00:39:15,220 --> 00:39:19,480
so that it's thought
to competitively

577
00:39:19,480 --> 00:39:23,800
interact or competitively
inhibit adenine function.

578
00:39:23,800 --> 00:39:30,670
Inhibitory
neurotransmitters, something

579
00:39:30,670 --> 00:39:35,170
called GABA, gamma-Aminobutyric
acid, and glycine

580
00:39:35,170 --> 00:39:38,980
are the two major CNS,
Central Nervous System

581
00:39:38,980 --> 00:39:40,520
neurotransmitters.

582
00:39:40,520 --> 00:39:45,670
GABA particularly is an
anti-anxiety neurotransmitter.

583
00:39:51,260 --> 00:39:56,010
And things like Xanax, which
I will get to today or Friday,

584
00:39:56,010 --> 00:39:59,900
are things which will be
agonists of GABA function.

585
00:39:59,900 --> 00:40:02,930
And sometimes,
neurotransmitters can be

586
00:40:02,930 --> 00:40:06,650
both excitatory and inhibitory.

587
00:40:06,650 --> 00:40:17,480
Acetylcholine,
for example, which

588
00:40:17,480 --> 00:40:21,110
is involved in connections
between nerves and muscles.

589
00:40:21,110 --> 00:40:27,560
Neuromuscular connections,
and also found in the CNS,

590
00:40:27,560 --> 00:40:30,950
can be both excitatory
and inhibitory.

591
00:40:30,950 --> 00:40:36,040
And serotonin-- and
I'll put dopamine

592
00:40:36,040 --> 00:40:40,720
on the same line for
space-- serotonin

593
00:40:40,720 --> 00:40:45,730
and dopamine, both
of which are kind

594
00:40:45,730 --> 00:40:51,940
of feel good
neurotransmitters, also

595
00:40:51,940 --> 00:40:58,560
involved in alertness
and other things.

596
00:40:58,560 --> 00:41:02,960
For dopamine-- locomotor
activity movement--

597
00:41:02,960 --> 00:41:06,090
they can be either
excitatory or inhibitory.

598
00:41:10,990 --> 00:41:13,030
What do they look like?

599
00:41:13,030 --> 00:41:15,740
Let me go on and then I'll show
you some pictures in a moment.

600
00:41:15,740 --> 00:41:16,360
All right.

601
00:41:16,360 --> 00:41:19,640
So how can something be
excitatory and inhibitory?

602
00:41:24,390 --> 00:41:29,380
What's downstream of
these neurotransmitters?

603
00:41:29,380 --> 00:41:34,260
The receptors.

604
00:41:34,260 --> 00:41:36,491
Good job.

605
00:41:36,491 --> 00:41:36,990
All right.

606
00:41:36,990 --> 00:41:40,650
Neurotransmitters,
ligands bind receptors.

607
00:41:40,650 --> 00:41:42,390
And the way the
neurotransmitters

608
00:41:42,390 --> 00:41:44,400
affect what they're
going to do is

609
00:41:44,400 --> 00:41:47,310
by binding the
appropriate receptor.

610
00:41:47,310 --> 00:41:52,830
So here are the receptors
for the neurotransmitters.

611
00:41:52,830 --> 00:41:56,590
And like the
neurotransmitters, there

612
00:41:56,590 --> 00:41:59,850
can be many different
kinds per synapse.

613
00:42:11,730 --> 00:42:15,710
There are two classes of
receptors that you should know.

614
00:42:15,710 --> 00:42:17,860
One are ion channels.

615
00:42:17,860 --> 00:42:21,240
They're receptors which
bind the neurotransmitter,

616
00:42:21,240 --> 00:42:22,430
and they open up.

617
00:42:22,430 --> 00:42:25,650
They're ligand
gated ion channels.

618
00:42:25,650 --> 00:42:29,310
But the other kind
are not ion channels.

619
00:42:29,310 --> 00:42:31,530
They bind the
receptor and then they

620
00:42:31,530 --> 00:42:33,720
activate a second
messenger system,

621
00:42:33,720 --> 00:42:35,550
as we talked about before.

622
00:42:35,550 --> 00:42:38,130
And it's the second
messenger system that

623
00:42:38,130 --> 00:42:41,100
later on opens an iron channel.

624
00:42:41,100 --> 00:42:43,500
They have names.

625
00:42:43,500 --> 00:42:49,895
So two classes, one
are the iron channels.

626
00:42:53,447 --> 00:42:57,190
They're called
ionotropic receptors.

627
00:43:00,170 --> 00:43:03,805
So they're ligand
gated ion channels.

628
00:43:10,800 --> 00:43:13,740
And the thing about these
is that their response

629
00:43:13,740 --> 00:43:22,300
is very rapid, in the
millisecond range.

630
00:43:25,560 --> 00:43:28,100
There's another class
of those receptors

631
00:43:28,100 --> 00:43:30,935
which activate ion channels.

632
00:43:34,840 --> 00:43:36,730
They are called metabotropic.

633
00:43:41,940 --> 00:43:44,510
It's the concept that is
more important than the term,

634
00:43:44,510 --> 00:43:47,090
but I'm giving you the
term for completeness.

635
00:43:47,090 --> 00:43:53,960
And they act via
a second messenger

636
00:43:53,960 --> 00:44:01,546
system that almost always
involves G proteins.

637
00:44:05,040 --> 00:44:06,075
And these are slow.

638
00:44:10,210 --> 00:44:15,150
Their response is at least
a second, often much greater

639
00:44:15,150 --> 00:44:15,860
than a second.

640
00:44:21,690 --> 00:44:22,750
OK.

641
00:44:22,750 --> 00:44:26,724
And let me, as the last
thing I'll tell you today,

642
00:44:26,724 --> 00:44:28,390
I'll show you-- if
we have a moment I'll

643
00:44:28,390 --> 00:44:29,848
show you some
pictures-- but I want

644
00:44:29,848 --> 00:44:33,550
to tell you that one
neurotransmitter can activate

645
00:44:33,550 --> 00:44:36,190
different kinds of the receptor.

646
00:44:36,190 --> 00:44:50,320
So one neurotransmitter can
activate greater than one type

647
00:44:50,320 --> 00:44:50,830
of receptor.

648
00:44:54,310 --> 00:44:57,250
And this was implicit
in the notion

649
00:44:57,250 --> 00:45:01,060
that neurotransmitters could be
both excitatory and inhibitory.

650
00:45:01,060 --> 00:45:08,920
For example, serotonin
binds to no fewer than 14

651
00:45:08,920 --> 00:45:11,470
different receptors.

652
00:45:11,470 --> 00:45:16,060
And one neuron can express
probably not all 14,

653
00:45:16,060 --> 00:45:20,020
but it could probably express
five different serotonin

654
00:45:20,020 --> 00:45:21,280
receptors.

655
00:45:21,280 --> 00:45:23,360
And they do different things.

656
00:45:23,360 --> 00:45:27,115
One of them is a ligand
gated sodium channel.

657
00:45:35,180 --> 00:45:46,340
Another type is G
protein coupled, so

658
00:45:46,340 --> 00:45:50,820
including both metabotropic
and ionotropic receptors.

659
00:45:54,060 --> 00:45:57,620
And to throw out at you
the last couple of slides,

660
00:45:57,620 --> 00:46:01,350
here are some of these amino
acids and small molecules

661
00:46:01,350 --> 00:46:05,230
that are neurotransmitters.

662
00:46:05,230 --> 00:46:08,040
And this really exemplifies
what I've said on the board.

663
00:46:08,040 --> 00:46:10,680
So I'm going to stop here now.