|WEEK #||TOPICS||LECTURE SUMMARIES|
|1||Introduction||Overview and discussion of the syllabus. Getting to know each other. Literature search using Pubmed. Really Simple Syndication (RSS) feeds to stay updated on the recent research papers – Bloglines.
Key neuroscience concepts for the next session.
|2||Neuromuscular Junction (NMJ) Synapses, Miniature End-Plate Potentials (mEPPs), and Quantal Hypothesis||Revolutionary papers by Paul Fatt and Bernard Katz were the first to explain how a chemical neurotransmitter interacts with its receptors to give rise to an electrical signal. They also provided the answers to the question how acetylcholine induces membrane permeability changes. They provided the basis for Katz's quantal hypothesis and for future studies of neurotransmitters both in neuromuscular junctions (NMJ) and in the central nervous system (CNS). The second paper investigates how the action of the neurotransmitter at the NMJ leads to the muscle contraction.|
|3||Central Nervous System (CNS) Synapses and Glutamate Receptors||There are two major classes of ionotropic glutamate receptors in the central nervous system, the N-methyl-D-aspartate (NMDA) and non-NMDA receptors (which are also divided into a a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate subtypes). This week is devoted to discussion of the basic properties of these receptors, the origin of miniature excitatory postsynaptic currents (mEPSCs), some of the elegant techniques used to study these currents.|
|4||CNS Synaptogenesis||Information processing by the brain relies on precise synaptic connections among neurons. These connections assemble neurons into massive networks of communicating cells. The properties of these networks are determined in part by their architecture. Neuronal cell-adhesion molecules connect presynaptic and postsynaptic neurons, mediate signaling across the synapse, and help define the architecture of neuronal networks. We will focus on how some of these cell-adhesion molecules establish the first contacts between neurons and how these contacts are either stabilized or eliminated depending on synaptic activity. We will also discuss how mutations in these cell-adhesion molecules might lead to impairments of neuronal wiring in the brain and consequently to autism.|
|5||Synaptic Fusion and SNAREs||Once a vesicle in a presynaptic terminal is filled with neurotransmitter it gets transported to the synaptic plasma membrane and docks. When a presynaptic action potential arrives, the vesicle fuses to the membrane and releases neurotransmitter into the synaptic cleft. The fusion step is mediated by membrane proteins called SNAREs (an acronym for SNAP (Soluble N-ethylmaleimide-sensitive factor Attachment Protein) REceptors). This week we will discuss the papers which investigate the role of SNAREs in the vesicle fusion.|
|6||Synaptic Release, the Calcium Sensor Hypothesis, and Synaptotagmin||Fast information transfer at the chemical synapse requires a regulated fast release of neurotransmitter vesicles. Action potentials arriving at the presynaptic terminal depolarize the membrane, leading to the opening of voltage-gated calcium channels (VGCCs) and a massive calcium influx. This calcium induces coordinated fast neurotransmitter exocytosis on a millisecond timescale. The earliest experiments by Bernard Katz and his colleagues already showed that calcium is necessary for fast regulated exocytosis, which led to the calcium sensor hypothesis. We will discuss the papers that have shown that synaptotagmin I is the calcium sensor for neurotransmitter release.|
|7||Synaptic Plasticity: Presynaptic Pair-Pulse Changes||Repetitive stimulation on a timescale of milliseconds to seconds can result in either short-term facilitation or depression of synaptic response. This phenomenon is attributed to two presynaptic mechanisms working in opposite directions: calcium accumulation in the presynaptic terminal and vesicle recycling. Interestingly, different synapse types in different brain regions often have different short-term plasticity characteristics. This week we will discuss data describing examples of short-term plasticity in different synapse types and models for how these phenomena occur.|
|8||Field Trip to the Laboratory of Mark Bear||Students will be able to watch in vitro slice physiology and in vivo recordings of visually evoked potentials (VEPs) in mice.|
|9||Synaptic Plasticity: LTP||One of the leading models for learning and memory posits that information is stored in the brain through long-term changes in synaptic strength. Synaptic plasticity is one of the most investigated topics in neuroscience. The leading plasticity paradigm is known as long-term potentiation or LTP. Nearly 10,000 papers have been written about LTP since its discovery in 1973. We will discuss the first description of LTP by Bliss and Lomo. The molecular mechanisms that underlie this form of plasticity have been hotly debated, with either or both pre or postsynaptic changes thought to be primarily responsible for LTP. The Isaac et al. paper describes data suggesting LTP can be mediated by a post-synaptic mechanism and reinterpret prior findings that had been understood to indicate a presynaptic mechanism.|
|10||Synaptic Plasticity: LTD||In addition to being stored, information in the brain also needs to be erased. Thus, synaptic plasticity is bidirectional. The counterpart to LTP is long term depression (LTD). Two major forms of LTD are mediated by activation of two different molecular pathways involving either NMDA receptors or metabotropic glutamate receptors (mGluRs). This week we will discuss two papers that dissect the molecular mechanisms of these different forms of LTD.|
|11||Synaptic Plasticity: STDP||Spike-time-dependent plasticity (STDP), another form of synaptic plasticity, occurs as a function of near synchronous pre- and postsynaptic neuronal activity. Depending on the precise firing sequence and the time-window, this activity can result in either LTP or LTD. Time-dependence is crucial for this form of plasticity, and it has been suggested that STDP provides the synaptic basis for learning in the central nervous system. STDP has been observed in various in vivo and in vitro systems. A seminal paper by Bi and Poo describes STDP in cultured neurons. A recent paper by Pawlak and Kerr suggests that dopamine modulates a corticostriatal form of STDP.|
|12||Persistent Neuronal Activity and UP-States||In some brain areas transient sensory stimuli can evoke neuronal activity characterized by discharge levels that remain elevated or suppressed for up to several seconds after the stimulus is gone. This type of neuronal activity is called persistent activity. Early studies recorded persistent activity in different brain areas of awake behaving primates during working memory tasks. The most popular mechanism hypothesized to explain persistent activity involves synaptic feedback loops. This week we will discuss studies of persistent activity in different brain areas in vitro.|
|13||Optogenetic Tools in Neuroscience||Optogenetics is a new and developing field of neuroscience that uses genetic techniques to control and probe specific neuronal circuits at millisecond-scale temporal resolutions. Optogenetic tools provide unique opportunities for neuroscientists to non-invasively activate or inactivate neuronal populations with tissue and cell-type specificity and high temporal precision. We will discuss one of the first papers that gave rise to the development of optogenetics in neuroscience and a more recent paper that uses optogenetic techniques to map a cortical circuit.|
|14||Oral Presentations||Students will individually (or in teams of two, depending on the number) present a paper related to the topics of the course.|