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Lecture12 - BioNB222 Cornell University Spring 2008 Ronald...

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BioNB222 Spring 2008 Cornell University Ronald Harris-Warrick 1 Lecture 12. Neurochemistry Reading Assignment Purves et al., Chapter 6. Summary: The major unique biochemical properties of the brain have to do with their synaptic interactions, which we discuss today. A number of different molecules can act as neurotransmitters or neuromodulators, including amino acids (glutamate, aspartate, ,glycine), biogenic amines (dopamine, norepinephrine, epinephrine, serotonin) and a large number of peptides (enkephalins, substance P, oxytocin, vasopressin). Each of these transmitters interacts with specific receptors and has unique roles in the general function of the brain. We discuss the life history of a transmitter, with details of their synthesis, packaging in vesicles for release, release and binding to post-synaptic receptors, and recycling or inactivation to terminate the synaptic event. Finally, we discuss the nicotinic acetylcholine receptor in more detail as an example of an ionotropic receptor. Learning Objectives 1. To learn some general facts about the major transmitter types, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin and the peptides such as enkephalin and substance P. 2. To study the stages in the life history of neurotransmitters, including details about their synthesis, packaging, receptor interactions and recycling. 3. To study the molecular structure and function of the nicotinic acetylcholine receptor as an example of how ionotropic receptor/channels work. Lecture Outline Neurochemistry is the study of the biochemical interactions within the brain that underlie neural activity. While researchers are studying every aspect of brain biochemistry, much of the present work is focused on the biochemistry of synaptic function, which we will discuss in this lecture. The most important compounds are the neurotransmitters, which carry the signal from one neuron to another. A. Brief Summary of Transmitters and Neuromodulators 1. Glutamate and aspartate : These are the most common excitatory transmitters in the brain; both appear to bind to the same receptors, and almost all study has focused on the actions of glutamate. There
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2 are at least four major classes of glutamate receptors, one of which is metabotropic and three of which are ionotropic. The NMDA receptor, named after its preferred artificial agonist, forms a channel which is blocked at normal resting potentials by extracellular Mg 2+ . This block is only relieved by depolarization of the cell. Thus, to activate these receptors, the cell must simultaneously be depolarized and bind glutamate. These receptors play critical roles in simple forms of learning and memory and in development, which we will discuss later in the course. The NMDA-activated channels tend to open and close more slowly than the other glutamate receptors (called AMPA and Kainate receptors); when both NMDA and AMP receptors are present at a synapse, the result is a rapid onset, slow offset epsp.
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