Behavioral Neuroscience Summers

text:The Basis of Neuropharmacology 8th Edition - Cooper, Bloom, Roth:read Chapter 105, 132-148 Rhythmicity & Behavior Sensory input for Rhythmicity Afferent path to the SCN Circadian Rhythms Efferent SCN output Integration of Rhythms into Behavior end     Acronyms/Abbreviations     Syllabus

Glu VIP AVP GABA 5-HT Figures of Rhythmicity Retina-RGC-SCN Molecular SCN

BIOLOGICAL RHYTHMS
III. Glutamate 			

	A.   Glu formed from NH2 and a-ketoglutarate (from glucose via Kreb's cycle)
	    
		1. universal cellular constituent
		   incorporated into the proteins of all cells

		2. a-ketoglutarate transaminase

			a. catabolism reverse
			
			b. glutamate is the immediate substrate for GABA

	B.  Receptors

		1. AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid) and
			   KA (kainate)   
 
			a. Glu-gated (opens) Nai+/Cai++/Ko+ channels = ionotropic
				i. membrane depolarization by increased Na+ conductance
					
			b. mediate fast, brief, intense excitatory synaptic transmission
				
				i. Glu and Aspartate (Asp)called excitatory amino acids
			
			c. composed of transmembranal protein subunits
			   AMPA: GluR1, GluR2/3, GluR4
			   KA: GluR5, GluR6, GluR7, KA1, KA2


		2. NMDA (N-methyl-D-aspartate)

			a. Glu-gated (opens) Cai++/Nai+/Ko+ channels

			b.  made of 5 subunits: NR1 + NR2A-D

			c. requires release of Mg++ binding in the channel

			d. facilitated by AMPA or KA depolarization  

				i. AMPA-R cluster near NMDA-R

				ii. Ý intracellular Na+ ® Ý NMDA channel activity


				iii. NMDA receptor channels without AMPA or KA are silent
					
					(1) silent synapses
						
					(2) AMPA may be trafficked in and out of synapses
					
				iv. postsynaptic density proteins link receptors		
					
					(1) PSD95, GKAP, Shank


		3. ionotropic receptor family bind multiple ligands
				
			a. NMDA binds Glu, Gly, Zn++ & polyamines extracellularly				
					
				i. Mg++ & PCP in channel	
					
				ii. steroids near lipid bilayer
							
				iii. Na+ intracellularly

		4. AMPA/NMDA play a pivotal role in synaptic plasticity, learning, 
		   long-term potentiation (LTP), long-term depression (LTD) 
			and developmental plasticity
					   
					   
		5. metabotropic (mGlu-R1-8)
 		   ACPD (trans-1-aminocyclopentane-1,3- dicarbyoxylate)
				
			a. slow synaptic responses

				i. affect synaptic transmission and synaptic placticity
					
					(1) D threshold Vm for action potential
						
			b. pre- or post-synaptic
					
				i. may be autoreceptors

			c. mGlu-R1 & mGlu-R5 activate Gp ® PLC ® DG/IP3 ® Ca++

			d. mGlu-R2  & mGlu-R3: Gi ®x AC ®cAMP

			e. mGlu-R4, mGlu-R6, mGlu-R7 & mGlu-R8: Gi ®x AC ®cAMP

	C. Reuptake by Na+ coupled neuronal (GTn)  and glial (GTg) transporters  

		1. both kinds of cells take up Glu to terminate signal and recycle
			
			a. protect cells from excitotoxic damage

		2. Glu taken up by glia converted to glutamine (Gln) then
			   transported back to the neuron 
			   
			a. Gln synthase

			b. mitochondrial glutaminase converts Gln ® Glu

	D. More glutamate/aspartate cells than all other cells in the vertebrate NS combined

		1. 10-100 billion

			a. transmitter for the numerous granule cells of the cerebellum

		2. retina to retinal ganglia to SCN (via RHT)
		
			a. Retinal ganglia Melanopsin + cryptochromes stimulate action 
			    potential and release of Glu and PACAP
		
		3. also cortical input to the hippocampus, striatum, and olfactory cortex
		
			a. hippocampus ® VTA

		4. gray matter of the spinal cord
	
		5. Invertebrates also use Glu as a major transmitter
	
			a. Evolutionarily ancient function
		
				i. e.g. sensory neurons are Glutamatergic