Summers

Neurobiology text: Principles of Neural Science - Kandel, Schwartz and Jessell: Read pages 280-296 for this lecture end

XVI. Neurotransmitters 			back to XV. Synaptic Connections

	A. meet the four following criteria 

		1. synthesized in the neuron

			a. often at the axon terminal for small molecules

				i. enzymes necessary for synthesis must be made
				    in cell body

		2. present in the synaptic terminal

			a. released in sufficient amounts and exerts an action
			    on a postsynaptic organ or effector organ

		3. exogenous application mimics endogenous release

			a. recognition and binding by postsynaptic receptors


			b. activates the same ion channels or 2nd messenger systems

		4. a specific mechanism removes it from the synaptic cleft

	B. Mature Neurons make use of the same transmitter substance(s)
	    at all of its synapses

		1. there may be more than one secretory substance

			a. colocalization

	C. Neuromodulators influence synaptic events less directly

		1. not responsible for direct transfer of action potential
		    from one neuron to another

		2. Released from Neurons, Glia, and other secretory cells

			a. alter the action of transmitters

				i. enhancing or reducing their effectiveness

			b. influencing: transmitter synthesis, release,
			   receptor interactions, reuptake, metabolism

				i. i.e. function like endocrines

					(1) hormones may be neuromodulators
					
		3. Criteria for neuromodulators are identical
		    to those for neurotransmitters

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XVII.  Acetylcholine		(CH3)3N+-CH2-CH2-O-C-CH3
		(ACh)
		
	A. substrates: choline (must come from the diet) and acetyl CoA
	    (Glycolysis and Kreb's)
		        
		1. synthetic enzyme: choline acetyltransferase (CAT)

			a. cytosolic   (most is synaptic)

			b. CoA left over

		2. degradative enzyme: acetylcholine esterase (AChE)

			a. membrane protein

			b. catabolites = choline and acetate

			c. turnover = 150ms	or	5,000 ACh molecules/s

	B. transmitter for: motor neurons of the spinal cord
	    \ all skeletal neuromuscular junctions

		1. all autonomic preganglionic neurons

			a. parasympathetic postganglionic neurons

		2. cells in the caudate-putamen nucleus involved in motor coordination 

		3. produced in the nucleus basalis 

			a. projections to the cerebral cortex and many parts of the brain

			b. these cells degenerate during Alzheimer's disease

		4. 2 specific populations in the limbic system

			a. septum to hippocampus  & habenulo-endopeduncular projections

			b. short axon striatal cells

	C. Muscarinic and Nicotinic Receptors 	(membrane proteins)

		1. M1 - M5

			a. slow response time (100 - 250 ms)

			b. act directly on ion channels 	

				i. open or close K+, Ca++, or Cl- channels

					(1) may lead to depolarization or hyperpolarization

			c. and activate 2nd messenger system (via G proteins)
			
				i. M1,3,5 PI hydrolysis
				
				ii. M2,4 cAMP

		2. Nicotinic

			a. four glycosylated peptide chains a, b, g, d   in muscle
			
			b. neuronal only a & b

			c. ACh binds to the a subunit

				i. binding causes conformational change

					(1) allows cations, not anions, to pass

XVIII. Catecholamines

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