Catalog description: A study of the synapses that mediate fast electrical excitation and inhibition in mammalian brain and how these synapses change with development and experience. The course will cover the molecular biology of glutamate, GABA and nicotinic acetylcholine receptor subtypes, experimental paradigms for studying long-lasting changes in synaptic function, and changes in animal behavior in relation to neuroplastic events.
Prerequisites: Consent of the instructor, ion channel IDP module recommended.
Expanded description and explanation: The brain is a complex network of neuronal connections. Each single neuron processes multiple inputs (potentially thousands), summing and integrating many analog elements to generate a frequency limited output that is subsequently serves as input to other neurons or target tissues outside of the brain. On top of these integrating and processing functions are aspects of modulation, conditional processing, and feedback which make the brain a dynamic and plastic system.
Neuronal processing primarily involves the transduction of chemical signals into short term or long term modulation of the cell's membrane potential. At the synapses a chemical neurotransmitter is released by the input (i.e.presynaptic) cells and this substance binds to specific receptors on the postsynaptic cell. We will discuss the two principle forms of neurotransmitter receptors, ionotropic (ion-channel) receptors, and metabotropic receptors. Multiple receptor subtypes exist for all known neurotransmitters. For glutamate, acetylcholine, serotonin and GABA some of the subtypes are ionotropic, while other subtypes are metabotropic. For other transmitters the receptor subtypes may all be metabotropic but couple to different intracellular pathways, e.g. cAMP or IP3.
Ionotropic receptors are also known as ligand-gated ion channels. The activation of these receptors directly and rapidly regulates membrane potential and the subsequent activity of the voltage dependent channels which generate nerve impulses. Metabolic receptors may have various effects including, but not limited to, modulating the ion channel receptors. While the effects of activating ionic receptors are rapid, occurring within milliseconds, and normally persisting for only milliseconds, the effects of activating a metabolic receptor occur more slowly, with latencies of many milliseconds or longer, and with effects that may persist indefintely.
The interactions between electrical signaling and other forms of intracellular signal transduction provides the basis for the phenomenon known as synaptic plasticity. The capacity for existing synapses to undergo changes inneurotransmission efficiency and the formation of newsynapses, are two mechanisms by which long-term changes in synaptic transmission persist in the CNS. Much has been learned about synaptic plasticity through the study of long-term potentiation (LTP), an electrophysiological phenomenon of increased synaptic efficacy following brief high frequency stimulation. Many characteristics of LTP (associativity/input specificity/cooperativity) make it well suited as a mechanism which could model learning and memory. We will study experimental models for synaptic plasticity, correlations with learning and memory in behaving animals, and how the processes have been studies at the molecular level with gene knockout experiments.
Evaluation of student performance: The course will be offered in seminar format. Depending on enrollment, thestudents will make between 2 and 5 presentation of published papers. Students will be graded on these presentations and this will account for 60% of their final grade. The students will also submit a final paper, in which they will describe: a testable scientific hypotheses, the experiments they would propose to conduct to test the hypothesis, and potential results and interpretations (4-6 typewritten pages, 40% of the final grade).
Faculty: Dr. Roger Papke will be the overall course director, and will direct students presenting papers pertaining to the basic features of synaptic function. Dr. Robert McNamara will assist in the course and will direct students covering some of the topics pertaining to synaptic plasticity.
Summary of topics:
Assigned reading: All assigned reading will be from original papers and review articles.