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 2. slow (indirect) - metabotropic

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

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

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

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 - excitatory at insect and crustacean NJ

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

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

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

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)

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

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

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

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

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

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

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

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