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Neurotransmitters

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.

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Neurotransmitters

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  1. 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

  2. Neurotransmitters B. Activity 1. fast-acting (direct) - ionotropic 2. slow (indirect) - metabotropic

  3. Neurotransmitters C. Classification 1. small molecules a. acetylcholine (ACh) b. biogenic amines c. amino acids

  4. Neurotransmitters C. Classification 2. neuropeptides a. from hypothalamus, pituitary, and other organs b. are often neurosecretory hormones c. also endorphins and enkephalins - bind to same receptors as opiates - endogenous opioids - placebo effect

  5. 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) - worm motor neurons, arthropod sensory neurons - curare is antagonist

  6. Neurotransmitters C. Classification - acetylcholinesterase breaks ACh down to acetate and choline - choline recycled in presynaptic neuron - blocked by some toxins (Sarin, tetanus)

  7. Neurotransmitters C. Classification 4. fast-direct transmitters b. glutamate - excitatory in vertebrate CNS - excitatory at insect and crustacean NJ

  8. Neurotransmitters C. Classification 4. fast-direct transmitters c. GABA-A (-aminobutyric acid) - inhibitory at ”glutamate” synapses

  9. Biogenic Amines/Monoamines - slow, indirect transmission - metabotropic A. Serotonin - derived from tryptophan Selective Serotonin Reuptake Inhibitors

  10. Biogenic Amines/Monoamines B. Catecholamines - derived from tyrosine - adrenergic neurons 1. epinephrine/adrenaline (hormone and neurotransmitter)

  11. 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

  12. 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

  13. Postsynaptic Activation A. Fast transmission channels (ACh) 1. nicotinic (activated by nicotine) a. stimulates skeletal muscle cells b. ion channel is receptor c. ligand binding briefly opens channel to Na+ - causes depolarization - excitatory postsynaptic potential - EPSP

  14. Postsynaptic Activation A. Fast transmission channels (ACh) 2. GABA-A a. receptors share homology with ACh receptors b. most prevalent in human brain c. cause hyperpolarization (IPSP)

  15. Postsynaptic Activation A. Fast transmission channels (ACh) 3. glycine a. hyperpolarization (IPSP) b. opens Cl- channels

  16. Postsynaptic Activation B. Slow channels 1. muscarinic (activated by muscarine) a. ion channels on separate membrane proteins b. ligand-binding activates G-protein complex c. activation of G-protein complex coupled to activation of ion channel

  17. Postsynaptic Activation B. Slow channels 2. cAMP levels can be increased or decreased depending on receptor subtype - effect can be to either open or close the ion channels

  18. Neuronal Integration A. Motor neurons as example 1. thousands of excitatory and inhibitory terminals on dendrites and soma - density often highest around hillock - proximity often confers preference

  19. Neuronal Integration A. Motor neurons as example 2. control frequency of firing of motor neuron - only excitatory stimuli can cause behavior change

  20. Neuronal Integration A. Motor neurons as example 3. these terminals are weak - multiple stimuli needed to trigger AP - prevents spontaneously activation of motor neurons

  21. Neuronal Integration B. Spatial summation 1. inputs from several synapses summed to simultaneously change Vm 2. often a battle between EPSPs and IPSPs

  22. Neuronal Integration C. Temporal summation 1. second potential follows close after first 2. “piggybacks” 3. amplifies potential 4. spatial and temporal often together

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