Behavioral Neuroscience Summers

C-Start Behavior Fundamentals of Neurocircuitry Senstory Stimulus for Startle Mauthner Cells - Response Gating Mauthner Efferent output Neuromuscular Function Integration of C-Start Circuitry and Behavior

text:Nestler pages 142-154 Glu DA ACh Transmitter Figures Figures of C-Start Behavior C-Start Circuitry end   Acronyms/Abbreviations

Escape Behavior
V. Glutamate (Glu) 			

	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: GluA1, GluA2/3, GluA4
			   KA: GluK1, GluK2, GluK3, GluK4, GluK5


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

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

			b.  made of 5 subunits: GluN1 + GluN2A-D (GluN3A-B)

			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. metabotropic (mGlu-R1-7)
 		   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

		5. Receptors are NOT static

			a. receptors and receptor subunits are trafficked into and out of the cell membrane

				i. AMPA subunits trafficked commonly

					1) Ds signal transduction qualities

					2) activates silent synapses

			b. / AMPA/NMDA play a pivotal role in synaptic plasticity, learning, 
			   long-term potentiation (LTP), long-term depression (LTD) 
				and developmental plasticity

	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. In vertebrates more glutamate/aspartate cells than all other cells in the NS combined

		1. 10-100 billion

		2. transmitter for the granule cells of the cerebellum

		3. also cortical input to the hippocampus, striatum, and olfactory cortex

		4. gray matter of the spinal cord