Lecture Notes

1 Introduction In this meeting I will introduce myself and the format for the course. After getting acquainted, with the students introducing themselves and their background in neuroscience (or lack thereof), we will discuss some basic concepts in neurophysiology that will help us understand the course material. In this meeting we will also learn about scientific manuscript writing, what to expect in a scientific paper and how each section is written. We will also introduce the subject of the first two papers. Lecture 1 (PDF)
2 Scientific reading, writing and learning mechanisms of simple invertebrates The "Cake article" will be returned with comments and briefly discussed. We will discuss how defensive reflexes of invertebrates can teach us about mechanisms underlying learning and memory. Lecture 2 (PDF)
3 Synaptic plasticity in rodent hippocampal slices Learning and memory can be studied at many levels of complexity. In this meeting we will see how pioneering research using brain slices discovered the basic physiological principals of plasticity in neuronal connections. We will discuss the impact of these findings on our understanding of memory and the molecular mechanisms underlying it. Lecture 3 (PDF)
4 Molecular mechanisms underlying LTP We will discuss how NMDA receptors were implicated in the induction of LTP and how this idea still holds years later as molecular tools have been added to study the events underlying synaptic plasticity. Lecture 4 (PDF)
5 Complicating the model of LTP We will discuss the phenomenon of long term depression (LTD), as well as mechanisms of LTP that do not require the NMDA receptor. Lecture 5 (PDF)
6 The Morris water maze The role of the hippocampus as an important brain structure necessary for performing learning related tasks was appreciated fully with the invention of the water maze. This elegant behavioral tool has been incorporated into the study of behavior at many levels, for understanding healthy brains and for the screening of rodent disease model systems. We will see examples of both. We will also discuss the abstracts written by the group. Lecture 6 (PDF)
7 Place cells After acquainting ourselves with the plasticity of neuronal circuits in the hippocampus and finding that this brain structure is necessary for rodents to find their place in the world, we can begin to investigate how it works. The discovery of neurons in the hippocampus that fire in a place-specific manner allows us to connect the plastic molecular events we measure in brain slices with awake, behaving animals foraging for food in an arena. We will see how place cells were discovered and how they are being studied today. Lecture 7 (PDF)
8 Field trip We will tour the Tonegawa lab in MIT building (Brain and Cognitive Sciences). We will see how many of the experimental techniques discussed in the course are carried out. Field Trip (PDF)
9 NMDA receptors and place cells In this meeting we will discuss two papers that were published together in one issue of the journal Cell as two parts of a three part story. Here, Susumu Tonegawa introduced new molecular tools that facilitated the deletion of a molecule necessary for synaptic plasticity from one part of the hippocampal network. We will see how this affected synaptic plasticity, spatial learning and place cell formation. Lecture 9 (PDF)
10 Hippocampal representation of space in contextual fear conditioning Learning to fear a potentially aversive context is a task that can be learned by rodents and measured by us. This task may depend on the hippocampus and its role as a cognitive map. In this meaning we will explore how hippocampal representation relates to contextual fear conditioning. Lecture 10 (PDF)
11 Synaptic tagging In this meeting we will return to brain slices with studies that attempt to understand some of the mechanics of how long term memories are formed and stored. Lecture11 (PDF)
12 Other aspects of place cells We will learn about the 'grid cells' of the entorhinal cortex. We will discus how this input information arriving at the hippocampus contributes to the formation of place cells. We will also see how analyzing place fields promotes our understanding of spatial memory in aging brains.  
13 Does LTP really happen in the brain? We will discuss examples of studies that were done to answer this question.  
14 Schemas' of memory Do memories of context in space remain in the hippocampus? Are they transferred to the cortex for long term storage? What are the temporal dynamics of such a process? Lecture 14 (PDF)