Behavioral Neuroscience, lecture on Substance P in Fear Conditioning
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Behavioral Neuroscience
Summers
Fear
Afferent Path for Fear
Amygdala
Fear Conditioning
Afferent Shock (US) Pathway
Efferent Output
Neuromuscular Production of Fear Potentiated Startle
Integration of Fear Conditioning
ACh
BDNF
Gephyrin
Enkephalin
Substance P
Fear figures
Fear Conditioning Circuitry
end     Acronyms/Abbreviations
Fear Conditioning
VI.V (6.5) Substance P (SP) 			

	A. One of the Tachykinin peptides    (rapid, move; fast acting)

		1. along with bombesin, substance K (neurokinin A),
		   neurokinin B (NKB; neuromedin K), neuropeptide K, neuropeptide g

			a. all derived from a single gene - ppT = preproTachykinin
			
				i. except NKB
				
		2. 11 amino acids
		
			a. Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2


	B. SP is regulated by tonic suppression of ppT in the dorsal root ganglion

			
		1. synaptic stimulaton of ganlionic neurons
		   suppresses PPT gene expression


		2. in Striatum: nigrostriatal DA induces ppT gene expression  
		   and increases SP in striatonigral neurons

			a. stimulated by D2, D2 control regulated by D1
			
			b. reciprocal innervation of substantia nigra and striatum


		3. SP colocalized with GABA and dynorphin in striatum

		4. SP with ACh in pontine neurons
				
		5. SP with 5-HT and TRH in raph
					
			a. also in descending 5-HT pathways that terminate
				    in ventral horn of the spinal cord
			
		6. with other peptides in sensory neurons
						
			a. Lordosis
				
		
	C. Tachykinin Receptors and Inositol Phosphate 2nd messenger

		1. High Affinity receptor: NK1 (SP type R)
		
			a. low affinity for NK2 & NK3

		2. GpPLC DG/IP3Ca++CalmodulinCAM Kinase


	D. Endocrine function 
		
		1. stimulates pancreatic enzyme secretion


	E. Enteric (GI) nervous system (part of the autonomic)

		1. Substance P innervates muscle, mucosa and interneurons
		
			a. powerful muscle contraction
		
		2. Distribution: small & large intestines, pancreas

		
	F. Spinal Cord
	
		1. Sensory transmitter in peripheral NS
		
			a. dorsal root cells (10-20% of 1o afferent fibers)
			
				i. colocalized with other peptides (VIP) and Glu
			
				i. also dorsal horn interneurons

			b. as with Lordosis
			
			c. SP is important in C-fiber nociceptive (pain) cells
			
				i. stimulated by capsaicin
				
				ii. SP released by dorsal root cells at the skin
				    stimulate blood flow, histamine and inflammation
					
						(1) blocked or reducd by capsaicin
			
			
		2. SP co-released with 5-HT in ventral horn
		
			a. stored together in large vesicles
			
				i. also sometimes with TRH
		
		
		3. also cross-regulation of release
		
			a. separate vesicles
			
			b. 5-HT enhances SP release via 5-HT2
			
			c. SP enhances 5-HT release
			
				i. SP also antagonizes 5-HT autoreceptor inhibition
				
					(1) positive feedback loop
					
					(2) augments neuronal action under conditions
					    of low neuronal activity
		

	G. Brain

		1. SP has a wide cell body distribution
		
			a. telencephalon: perikarya in striatum, nucleus accumbens
			   amygdala, habenula
			   
			   	i. SP/Glu/Enk cells in BLA project to MeA
				
					(1) MeA  VMH
				
				ii. SP/GABA/Dyn cells in striatum project to substantia nigra
				
					(1) striatonigral pathway
			
			b. diencephalon: anterior hypothalamus, ventral hypothalamus
			
				i. MeA  VMH are Glu/Enk/SP synapses
				
					(1) Glu-AMPA, Enk-m, SP-NK1
					
					(2) VMH  PAG
				
				ii. SP implicated in VMH for lordosis
				
					a. VMH cells E2 and P receptors
					   also make SP
			
			c. mid/hindbrain: Edinger-Westphal nucleus, median raph,
			   midbrain central gray (MCG; PAG), LateroDorsal Tegmentum (LDT),
			   Nucleus of the Solitary Tract (NST)
			   
			   	i. VMH  PAG/MCG: Enk-m, SP-NK1
				
				ii. SP implicated in MCG for lordosis
			   
			d. cranial nerves: trigeminal, glossopharyngeal, vagus

VII. Efferent Output