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Transcript
Neurotransmitters A. Criteria 1. must mimic presynaptic effects if administered exogenously 2. must be released during activity of presynaptic neuron 3. action must be blocked by same agents that block natural transmission Neurotransmitters B. Activity 1. fast-acting (direct) - ionotropic - receptor coupled directly to ion channel QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Neurotransmitters B. Activity 2. slow (indirect) - metabotropic - receptor coupled to membrane receptor - activation of second messenger pathways QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Neurotransmitters B. Activity 2. slow (indirect) - metabotropic - or modulates opening of channels in response to voltage changes (neuromodulation) QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Neurotransmitters C. Classification 1. small molecules a. acetylcholine (ACh) b. biogenic amines c. amino acids Neurotransmitters C. Classification 2. neuropeptides (from all areas of nervous system) a. also from hypothalamus, pituitary, and other organs b. are often neurosecretory hormones c. also endorphins and enkephalins - bind to same receptors as opiates - endogenous opioids Neurotransmitters C. Classification 3. most are highly conserved 4. fast-direct transmitters - only one type synthesized by individual neurons a. ACh - cholinergic neurons (i. e., neuromuscular junction) - curare is antagonist Neurotransmitters C. Classification - acetylcholinesterase breaks ACh down to acetate and choline - choline recycled in presynaptic neuron - blocked by some toxins (Sarin, tetanus) Neurotransmitters C. Classification 4. fast-direct transmitters b. glutamate - excitatory in vertebrate CNS QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. NMDA receptors are ionotropic glutamate receptors these modulate Ca++ channels QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Neurotransmitters C. Classification 4. fast-direct transmitters c. GABA-A (-aminobutyric acid) - inhibitory at ”glutamate” synapses QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. d. glycine - inhibitory - can modulate glutamate QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. d. glycine - inhibitory - some have chloride ionophore function QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Biogenic Amines/Monoamines - slow, indirect transmission - metabotropic A. Serotonin - derived from tryptophan Selective Serotonin Reuptake Inhibitors Biogenic Amines/Monoamines B. Catecholamines - derived from tyrosine - adrenergic neurons 1. epinephrine/adrenaline (hormone and neurotransmitter) Biogenic Amines/Monoamines B. Catecholamines - derived from tyrosine 2. norepinephrine/noradrenaline (hormone and neurotransmitter) - many psychoactive drugs mimic NE - amphetamines - cocaine (prevents inactivation of NE) 3. dopamine Biogenic Amines/Monoamines C. Release and uptake 1. similar release to ACh 2. rapid inhibition following release a. reuptake to presynaptic neurons b. monoamine oxidase in presynaptic neuron Regulation Desensitization/Down-regulation - initially a decrease in affinity - long-term becomes loss of receptors Regulation Super-sensitivity/Up-regulation - seen in synapses that are rarely used Regulation Long-term potentiation - an increase in the strength of synaptic transmission with repetitive use that lasts for more than a few minutes - in hippocampus can be triggered in less than 1 second of intense synaptic activity Regulation Long-term potentiation Model: 1. afferent stimulus causes release of glutamate 2. glutamate binds to NMDA and non-NMDA receptors on postsynaptic membrane (Na+ influx) 3. EPSP causes removal of Mg++ which normally hinders Na+ and Ca++ influx 4. Ca++ influx leads to activation of postsynaptic protein kinase, which induces an LTP. QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.
