Behavioral Neuroscience, lecture on Glutamate
USD Department of Biology
Behavioral Neuroscience
Summers
Aplysia Behavior
Sensory Stimulation of Siphon Withdrawl
Motor Output driving Siphon Withdrawal
Gating
Conditioning & Memory
text:Kandel pages 1248-1257      Nestler pages 142-154
Glu
ACh
5-HT
Aplysia and Siphon Withdrawl
Siphon Withdrawl Circuitry
end     Acronyms/Abbreviations     Syllabus
Siphon Withdrawal
IV. Glutamate (Glu) 			

	A.   Glu formed from NH2 and a-ketoglutarate (from glucose via Kreb's cycle)
	    glutamate
		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. 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
	
	E. Invertebrates also use Glu as a major transmitter
	
		1. Evolutionarily ancient function
		
		2. Aplysia and Leech sensory neurons are Glutamatergic
		
			a. multiple sensory receptor types
			
				i. invertebrate Touch, Pressure, and Nociceptive (Pain)
				
					(1) all Glu

V. Motor Output