Behavioral Neuroscience, lecture on VIP in Biological Rhythms
USD Department of Biology
Behavioral Neuroscience
text:The Basis of Neuropharmacology 8th Edition - Cooper, Bloom, Roth:read Chapter 11
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
Figures of Rhythmicity
Molecular SCN
VI. VIP 			

	A. Vasoactive Intestinal Peptide (VIP) is in the peptide family
	   called Secretins
		1. also includes secretin,  glucagon, GIP,  GHRH and
		   Pituitary adenylyl cyclase activating polypeptide (PACAP)
		2. 28 amino acids
	B. Neuropoietic cytokines stimulate VIP secretion

		1. e.g. ciliary neurotrophic factor, (CNTF)

			a. via Jak/STAT

				i. STAT transcription factors bind
				   cytokine responsive element (CyRE)
				ii. VIP gene also linked with CRE enhancer
		2. VIP colocalized with ACh in parasympathetic neurons
		   and cortical neurons
			a. in PNS more VIP released at high stimulus frequencies
				i. 10 Hz vs 2 Hz
			b. VIP augments release of ACh
				i. VIP increases ACh affinity
				   for muscarinic receptors
			c. VIP stimulates blood vessel dilation
				i. VIP potentiates ACh stimulation of
					 blood vessel dilation

		3. VIP colocalized with GABA in cortex and SCN

		4. VIP colocalized with NO in SCN and pineal
		5. VIP colocalized with galanin and/or SP in spinal cord
	C. VIP Receptors: VPAC1&2   (aka PVR; also bind PACAP)
		1. family of 7tm (transmembrane) receptors: PAC1, VPAC1, VPAC2
			a. family of receptors for secretin, GHRH, CRF, PACAP,
			   glucagon, glucagon-like peptide, parathyroid hormone,
			   calcitonin, calcitonin gene-related peptide
		2. VPAC1/HVR1/PVR2 Inhibited by cortisol/corticosterone (F/B)
			a. negative glucocorticoid response element (nGRE)
			   in VPAC1 gene
			b. major site of VPAC1 is the lungs
		3. VIP receptors on both neurons and glia
			a. VIP can regulate and stimulate glial and neuronal function
				i. neurotrophic and neuroprotective actions
				   of VIP are via astroglial action
	D. 2nd messenger: cAMP and Inositol Phosphate


		2. VPAC1 also GpPLCIP3Ca++CalmodulinCAM Kinase
	E. Endocrine functions of VIP
		1. GastroIntestinal (GI) function

			a. stimulates gastric pepsin secretion

			b.  inhibits GI motility & growth
			c. increases gastric, pancreatic, and intestinal blood flow
				i. VIP is a potent vasodilator
		2. Heart 
			a. coronary vasodilation
			b. VIP increases heart contractility and rate
		3. Lungs - bronchodilation

		4. VIP stimulates prolactin secretion from the pituitary

		5. VIP stimulates adrenal medulla catecholamines (NE, Epi)

		6. VIP present in ovary
			a. stimulates oocyte maturation and steroidogenesis

		7. VIP produced by immune cells
			a. anti-inflammatory molecule
				i. direct inhibition of proinflammatory cytokines
				   like TNFa
			b. inhibits mitogen-activated proliferation of T cells
				i. VIP inhibits IL2 production
	F. Enteric (GI) nervous system (part of the autonomic)

		1. VIP innervates muscle, mucosa and interneurons

		2. VIP is also transmitter for interneurons

		3. Distribution: stomach, small intestine, large intestine

	G. Spinal Cord
		1. 1o afferent neurons in the dorsal root ganglia
		   projecting to the dorsal horn
			a. Lordosis
				i. colocalized with SP
				ii. highest binding of VIP in lumbar and sacral regions
			b. colocalized with galanin
		2. parasympathetic and sympathetic neurons
		3. neurons in the dorsal horn
		   lamina X and the intermediolateral nucleus

		4. VIP binding occurs early in spinal cord

			a. dense VIP binding sites

			b. VIP regulates morphogenic events
			   releasing diffusible signals from glial cells
	H. VIP in the Brain

		1. VIP is found in cerebral cortex, hippocampus, thalamus,
			bed nucleus of the stria terminalis (BNST), hypothalamus,
			amygdala, superior colliculus, and dorsal raph

			a. highest concentrations of VIP in the BNST, amygdala
			   and cerebral cortex 

		2. Cerebral Cortex

			a. cerebral blood flow
			b. regulation of cerebral energy metabolism
			c. neuronal survival

		3. VIP in Hippocampal interneurons
			a. pryamidal cells have both VPAC1, VPAC2 receptors
			b. regulates electrical activity
			c. VIP produces impairment in previously learned behaviors
			d. but...VIP important to successful memory acquisition

		4. BNST projects dense VIP fibers in a major bi-directional

		   	a. linking the amygdala, medial hypothalamus and pre-optic area

			b. VIP plays a rolein processing of autonomic,
			   endocrine and somatomotor information
			   related to motivation and emotional processing
			a. VIP may inhibit stress-motivated behaviors

		5. VIP in the Hypothalamus 
			a. SCN (suprachiasmatic nucleus)
				i. regulates circadian rhythms (biological clock)
				ii. Light, synaptic activity, lactation, adrenal hormones
				     VIP gene expression in SCN core
				iii. VIP mRNA exhibits diurnal oscillations
				     high VIP levels during scotophase

			b. VIP cells in SON, PVN

				i. VIP inhibits food intake
					(1) and regulates food-induced increases in ACTH/B

		6. Superior colliculus VIP
			a. VIP neurons project to the
			   lateral geniculate nucleus of the thalamus
				i. VIP may be involved in the motor coordination
				  of visual reflexes

		7. dorsal raph
			a. VIP enhances rapid eye movement (REM) sleep

VII. Arginine Vasopressin (AVP)

VIII. g-Aminobutyric Acid (GABA)

IX. Serotonin (5-HT)

X. Circadian Rhythms