Course Meeting Times
Lectures: 1 session / week, 2 hours / session
Prerequisites
There is no strict prerequisite for this course, but some knowledge of molecular biology and/or neuroscience is recommended. We expect that all students will encounter some unfamiliar terminology while reading research papers from the primary literature, regardless of their academic background. We will go over important terminology in class, but students should also be prepared to do their own internet searches for unfamiliar terminology and/or bring their questions to the next class session.
Course Description
Our brains are remarkably adaptable throughout our lives. Individual brain cells called neurons form synapses, sites of physical connection and communication between neurons, and then repeatedly rewire those connections in response to new experiences or to neuronal cell death caused by injury, disease, or aging. In this course, we will explore how neurons establish their synapses in the healthy brain during childhood and later in life, and how this process goes awry in disease states.
More specifically, we will discuss how the brain forms its synapses early in life, stabilizes a subset of those synapses for long-term maintenance, and continues to add and remove synapses throughout life. We will then explore synapse dysfunction in diseases such as autism and Alzheimer’s disease, which involve abnormal increases or losses of synaptic connections, respectively. We will also consider synapse remodeling, a process of adding and removing synaptic connections to optimize our brain network, in the context of neuroinflammation, recovery from traumatic brain injury, and psychological trauma following prolonged stress.
This course will be discussion-based. Each session will provide an opportunity for students to tackle two related papers from the primary scientific literature, ask questions to hone their understanding of the methodology and data presented in the papers, and practice critiquing the papers. Students will also have an opportunity to build their written and verbal communication skills through a written assignment and an oral presentation. The written assignment will focus on proposing an experiment in a mock mini-grant proposal, which students will draft and then refine together during one of the class sessions. In the oral presentation, students will practice explaining and critiquing a paper from the scientific literature.
To provide real-life experience with the techniques used in the papers we discuss in class, we will see a demonstration of brain imaging in an MIT neuroscience laboratory, which will exemplify the experimental methods needed to generate the scientific figures analyzed in class. To facilitate discussion about career paths in the biomedical sciences, we will go on a field trip to an industry laboratory, where we will hear from industry scientists about their career journeys and learn about ongoing research behind neuromuscular diseases, a family of rare genetic disorders characterized by muscle degeneration due to alterations in the peripheral nervous system.
This course will introduce students to a variety of methodologies used not only in the field of synapse dynamics but more generally across many disciplines in the field of molecular medicine. This class may be particularly beneficial to students interested in careers in biomedical research and/or medicine, but we welcome all students who are excited about learning how to read the primary scientific literature, understanding the process of critical scientific reasoning, and learning about how our brains remodel their connections in healthy and diseased states.
Course Format
This course is discussion-based and will meet once per week for two hours. Each week, we will focus on two papers from the primary literature. Students are expected to read both papers carefully, bring their thoughts/questions to class and/or send them by e-mail to the instructors before class, and be prepared to participate actively in the discussion. At the end of each class, the instructors will provide a brief introduction to the papers that will be discussed in the next class session, to provide context for the papers and go over any important new experimental methods and terminology.
We will spend one class session on a field trip to Vertex Pharmaceuticals, half a class session on an imaging demonstration in the neurobiology laboratory of MIT Professor Elly Nedivi, one class session workshopping students’ mock grant proposals, and one class session on students’ final oral presentations (see Assignments for details).
Course Objectives
The major goal is to learn to read and critique the primary research literature. By the end of the course, students should be able to do the following:
- Identify the central questions in a paper from the primary literature.
- Identify the experiment(s) and key control(s) that were performed to answer that question.
- Identify the authors’ conclusions and the data that support each conclusion.
- Evaluate whether each conclusion is well supported by the data presented in the paper.
- For any claims that are not well supported, propose experiments the authors could perform to clarify the ambiguity.
- Propose new experiments that could further test or extend the findings of the paper.
More specifically, through our discussions and the written assignment, students will become more familiar with basic principles of experimental design, learning to understand the use and design of control experiments and to design new experiments with appropriate controls.
The papers we read each week will focus on a topic specified in the syllabus for that specific week. By the end of the course, we hope students also will learn about aspects of the field of neurobiology, will develop a broad familiarity with how synapses remodel during the course of normal development and in the context of various diseases, and will understand the advantages and disadvantages of different techniques and experimental systems that are used to investigate synapse remodeling.
Grading and Attendance Policies
This course is worth 6 units and is graded pass/fail. A student who attends the course, actively participates in discussions, and completes both written and oral assignments in a satisfactory manner will receive a passing grade.
Field Trip and Imaging Technique Demonstration
In the Boston area, we are surrounded by labs that are at the forefront of biology and neuroscience research in both academia and industry. We will spend one class session on a field trip to Vertex Pharmaceuticals, where we will hear from scientists about their career journeys and learn about their ongoing research. The CRISPR/Cas9 gene delivery system has revolutionized approaches to gene therapy and opened the door to personalized medicine. During our visit to Vertex Pharmaceuticals, we will learn about CRISPR/Cas9 approaches to treat neuromuscular disorders and cystic fibrosis. This experience will introduce students to a variety of methodologies used not only in the field of synapse dynamics but more generally across many disciplines in the field of molecular medicine.
To provide real-life exposure to some of the techniques used in the papers we discuss in class, students will observe a demonstration of in vivo 2-photon imaging of the mouse brain to view how synapses on the dendritic arbor of a single neuron behaves in the brain of a live mouse. This visit to the MIT neuroscience laboratory of Professor Elly Nedivi will exemplify experimental methods used to generate some of the scientific figures discussed in class prior to the demonstration. More specifically, students will observe how the genetic labeling of individual neurons and their synapses allows studies of how synaptic connections are made and removed in real-time. Students also will observe how specific gene targets are validated using the polymerase chain reaction (PCR), which amplifies the DNA sequence of a gene and can be used to determine the presence/absence of a specific fragment belonging to the gene of interest. Both techniques are applied broadly in the field of neurobiology.
Classroom Culture
All members of this class are expected to contribute to a respectful, welcoming, and inclusive environment for all other members of the class. We welcome students of all backgrounds, beliefs, ethnicities, national origins, gender identities, sexual orientations, religious and political affiliations—and other visible and non-visible differences. We (the instructors, Joe and Dalila) will provide a link to a feedback platform where students can send us any concerns about the class environment, our teaching, or their interactions with other students in the class. We will also provide feedback forms specifically about our teaching midway through the semester and at the end of the semester.
Calendar
| Week | Topics |
|---|---|
| 1 | Introduction |
| 2 | Synapse Plasticity: Developing Brain |
| 3 | Synapse Plasticity: Aging Brain |
| 4 | Sensory Experience-Dependent Plasticity—Part 1 |
| 5 | Sensory Experience-Dependent Plasticity—Part 2 |
| 6 | Learning-Induced Synaptic Plasticity |
| 7 | Neurodevelopmental Disorders: Autism and Fragile X Syndrome |
| 8 |
Workshop Mock Grant Proposals Rough draft of mock grant proposal due |
| 9 |
Neurodegeneration: Alzheimer’s Disease Final draft of mock grant proposal due |
| 10 | Injury: Peripheral Nerve Injury and Traumatic Brain Injury |
| 11 | Field Trip to Vertex Pharmaceuticals |
| 12 |
Fear and Trauma Deadline to choose paper for final presentation |
| 13 | Nedivi Lab Visit: Technique Demonstrations |
| 14 | Final Oral Presentations and Wrap-up Discussion |
