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An Introduction to Neurotransmission William Wisden Dept of Clinical Neurobiology INF 364 [email protected] Fundamental Neuroscience - second edition Squire, Bloom, McConnell, Roberts, Spitzer, Zigmond Academic Press, 2003 http://www.indstate.edu/thcme/mwking/home.html http://www.indstate.edu/thcme/mwking/nerves.html http://faculty.washington.edu/chudler/neurok.html http://faculty.washington.edu/chudler/chnt1.html Explore the Brain and Spinal Cord The Neuron A neuron The action potential Hodgkin & Huxley, 1939 Rate of action potential firing is information The dendrite Differences between axons and dendrites Axons Dendrites Take information away from the cell body Bring information to the cell body Smooth Surface Rough Surface (dendritic spines) Generally only 1 axon per cell Usually many dendrites per cell No ribosomes Have ribosomes Can have myelin No myelin insulation Branch further from the cell body Branch near the cell body Dendrites constitute a kind of neural microchip for complex computations Rate of action potential firing is information Frequency code of impulses within the axons Place/topological code depending on which axons are active Chemical synapse Axon-dendrite Axo-axonic Axon-soma Passing information between neurons Gap junctions -electrical transmission fast both directions Chemical transmission slower - unidirectional integrative amplifies and regenerates the signal The synapse IN OUT Calcium entry is excitatory Calcium is a second messenger which binds to target proteins e.g. Calmodulin Electrical Trigger for Neurotransmission Ca2+ Action potential Axon Terminal Neurotransmitter Mobilization and Release Diffusion of Neurotransmitters Across the Synaptic Cleft Spine Dendrite Action potential Depolarization Ca2+ Electrical properties How is the action potential generated? http://faculty.washington.edu/chudler/ap.html OUT EXCITATORY + IN INHIBITORY - INHIBITORY - Look at the animation! http://faculty.washington.edu/chudler/ap.html Neurotransmitters Excitatory Excitatory Inhibitory Simple transmitters: g-aminobutyric acid (GABA) glutamic acid (glutamate) acetylcholine (Ach) OUT Cl- Na+ Na+ Cl- Na+ Na+ GABAA receptor Inhibition IN Glutamate/AMPA receptor Acetylcholine receptor Excitation Neurons and glial cells The process of chemical neurotransmission can be divided into five steps 1. Synthesis of the neurotransmitter in the presynaptic neuron 2. Storage of the neurotransmitter and/or its precursor in the presynaptic nerve terminal 3. Release of the neurotransmitter into the synaptic cleft 4. Binding and recognition of the neurotransmitter by target receptors 5. Termination of the action of the released transmitter Life cycle of a neurotransmitter An excitatory (glutamatergic) synapse A synapse using g-aminobutyric acid (GABA) A synapse that uses acetylcholine (ACh) Simple circuits Feed-forward inhibition Negative feedback Feedback inhibition Neocortex Interneuron - uses GABA Pyramidal neuron - uses glutamate Ionotropic and metabotropic receptors Fast Slow Ion flow in/out Second messenger cascades milliseconds seconds Ionotropic Metabotropic OUT Cl- Na+ Cl- Na+ GABAA receptor Inhibition IN Glutamate/AMPA receptor Excitation Neuromodulators Slow synaptic transmission
