Syllabus

Course Meeting Times

Lectures: 1 session / week, 2 hours / session

Prerequisites

Basic knowledge of cell biology, molecular biology and neuroscience will be beneficial.

At least one of the following courses:

7.03 Genetics
7.05 General Biochemistry
7.06 Cell Biology
7.28 Molecular Biology

Course Description

The mammalian brain easily outperforms any man-made supercomputer with respect to computing time and process complexity. The brain adapts and changes constantly in response to external stimuli. Most importantly, the brain enables us to continuously learn and remember new things. A single experience, such as touching a hot plate, witnessing a tragedy, or experiencing the shocking taste of durian fruit can be remembered for life.

What are the molecular mechanisms that lead to learning and memory? How do nerve cells, inter-neural connections (synapses) and brain circuits change over time to store information? Electrical activity in the nervous system controls the expression of a set of genes that can affect neuronal function. What are the cellular roles that activity-regulated gene products play to implement changes in the brain?

We will discuss the molecular mechanisms of neuronal plasticity at the synaptic, cellular and circuit levels. We will consider fundamental neurobiological processes, such as

  1. synapse formation,
  2. synaptic growth and stabilization,
  3. synaptic transmission,
  4. axonal and dendritic outgrowth, and
  5. circuit formation, with some focus on the visual system.

We will learn about the roles of some activity-regulated genes in these processes, and we will study their functions in various experimental systems, such as dissociated neuronal cultures, cultured brain slices, and the living brain. In addition, we will learn about the tools and techniques employed in modern neuroscience research. Our goal will be to understand molecular mechanisms the brain employs to bring about the complex phenomena of learning and memory.

Goals

The goals of this course are:

  1. teach students how to read and analyze the primary research literature and critically assess scientific experiments;
  2. convey an understanding of classical and modern techniques in molecular neuroscience; and
  3. give students experience presenting scientific data to an audience.

Format

We will have weekly sessions. The class will rely on reading original research papers from the scientific literature and will involve group discussions. Students are expected to read the papers ahead of each session and to submit two questions to the instructor by 5 pm the previous day. These questions will be talked through in a round-table discussion.

The first session will comprise an informal mutual introduction to get to know each other and an introductory lecture by the instructor. Later sessions will comprise student-driven round-table discussions of both of the assigned papers, as well as a brief overview by the instructor of the techniques and background necessary to understand the following week's papers.

Requirements

Grading in this course is pass/fail and will be based on regular participation in the weekly meetings as well as on the two assignments. Attendance at all meetings is very important. If absence is unavoidable, the instructor should be notified ahead of time and a make-up assignment will be provided.

Calendar

WEEK # TOPICS KEY DATES
1 Introduction  
2 Cellular correlates of memory and memory erasure: Long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength  
3 The NMDA receptor, a gatekeeper for synaptic plasticity  
4 Making silent synapses talk: Activation of the NMDA receptor recruits AMPA-type glutamate receptors to synaptic sites  
5 AMPA receptor endocytosis as a key mechanism for regulating synaptic strength  
6 Metabotropic glutamate receptors (mGluRs) are potent mediators of long-term synaptic depression(LTD)  
7 Synaptic scaling as a mechanism to globally tune synapse strength  
8 Neurite outgrowth: constructing elaborate neuronal circuits The written proposal (midterm assignment) for future scientific research is due
9 Synaptogenesis  
10 Field trip to the Eli and Edythe L. Broad Institute and the Nedivi Lab  
11 Activity-induced synapse turnover  
12 Activity-regulated gene expression in neurons Paper selection for oral presentation due
13 Final assignment and closing remarks Oral presentations