NeurotransmittersA. Criteria

1. must mimic presynaptic effects if administered exogenously2. must be released during activity of presynaptic neuron3. action must be blocked by same agents that block natural transmission

NeurotransmittersB. Activity

1. fast-acting (direct) - ionotropic2. slow (indirect) - metabotropic

NeurotransmittersC. Classification

1. small moleculesa. acetylcholine (ACh)b. biogenic aminesc. amino acids

NeurotransmittersC. Classification

2. neuropeptidesa. from hypothalamus, pituitary, and other organsb. are often neurosecretory hormonesc. also endorphins and enkephalins

- bind to same receptors as opiates- endogenous opioids- placebo effect

NeurotransmittersC. Classification

3. most are highly conserved4. fast-direct transmitters

- only one type synthesized by individual neuronsa. ACh

- cholinergic neurons (i. e., neuromuscular junction)- worm motor neurons, arthropod sensory neurons- curare is antagonist

NeurotransmittersC. Classification

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

NeurotransmittersC. Classification

4. fast-direct transmittersb. glutamate

- excitatory in vertebrate CNS- excitatory at insect and crustacean NJ

NeurotransmittersC. Classification

4. fast-direct transmittersc. GABA-A (-aminobutyric acid)

- inhibitory at ”glutamate” synapses

Biogenic Amines/Monoamines

A. Serotonin - derived from tryptophan

Selective Serotonin Reuptake Inhibitors

- slow, indirect transmission - metabotropic

Biogenic Amines/Monoamines

B. Catecholamines - derived from tyrosine

- adrenergic neurons1. epinephrine/adrenaline (hormone and neurotransmitter)

Biogenic Amines/Monoamines

B. Catecholamines - derived from tyrosine2. norepinephrine/noradrenaline (hormone and neurotransmitter)

- many psychoactive drugs mimic NE- amphetamines- cocaine (prevents inactivation of NE)

3. dopamine

Biogenic Amines/Monoamines

C. Release and uptake1. similar release to ACh2. rapid inhibition following release

a. reuptake to presynaptic neuronsb. monoamine oxidase in presynaptic neuron

Postsynaptic ActivationA. Fast transmission channels (ACh)

1. nicotinic (activated by nicotine)a. stimulates skeletal muscle cellsb. ion channel is receptorc. ligand binding briefly opens channel to Na+

- causes depolarization- excitatory postsynaptic potential- EPSP

Postsynaptic Activation

A. Fast transmission channels (ACh)

2. GABA-Aa. receptors share homology with ACh receptorsb. most prevalent in human brainc. cause hyperpolarization (IPSP)

Postsynaptic Activation

A. Fast transmission channels (ACh)

3. glycinea. hyperpolarization (IPSP)b. opens Cl- channels

Postsynaptic Activation

B. Slow channels1. muscarinic (activated by muscarine)

a. ion channels on separate membrane proteinsb. ligand-binding activates G-protein complexc. activation of G-protein complex coupled to activation of ion channel

Postsynaptic Activation

B. Slow channels2. 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 example1. 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 example2. control frequency of firing of motor neuron

- only excitatory stimuli can cause behavior change

Neuronal Integration

A. Motor neurons as example3. these terminals are weak

- multiple stimuli needed to trigger AP- prevents spontaneously activation of motor neurons

Neuronal Integration

B. Spatial summation1. inputs from several synapses summed to simultaneously change Vm

2. often a battle between EPSPs and IPSPs

Neuronal Integration

C. Temporal summation1. second potential follows close after first2. “piggybacks”3. amplifies potential4. spatial and temporal often together