Behavioral Neuroscience, lecture on Behavioral Rhythmicity
USD Department of Biology
Behavioral Neuroscience
text:The Basis of Neuropharmacology 8th Edition - Cooper, Bloom, Roth:read
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
XII. Integration of Rhythms into Behavior: Activity 			

	A. Spontaneous firing in SCN neurons 
		1. VIP  VPAC2 in shell AVP neurons maintains membrane depolarization
		    threshold  usual Na+  Ca++  K+
			a. slowly inactivating1 then fast2 Na+ channels 
			b. slow opens around -60 mV
				i. depolarizing activates fast Na+ and highV Ca++ channels

		2. Per gene activity requires Na+ depolarization
			a. VPAC2  CREB  CRE activates Per
		3. PER + CRY + CK1e  Rev/Erba + Rora
			a. REV/ERBa + RORa  Clock + BMal
			b. strongest Per rhythm in SCN shell
			c. Per activity  VIP + AVP
		4. CLOCK + BMAL  Per + Cry  PER + CRY + CK1ePer + Cry 
		   via build up + interaction with CLOCK/BMAL at E-box

			a. photophase build-up silences Per + Cry at night
			b. degradation of PER/CRY during scotophase 
			    absent at the onset of photophase
		5. Action potentials are terminated by K+ channels 
			a. some K+ channels are independent of Ca++ and some dependent 
	B. During the night decreasing chance of SCN firing ® 2-4 Hz frequency 
		1.  K+ efflux hyperpolarizes SCN neurons
			a. slow outward flux
				i. TEA sensitive K+ channel
		2. Slower de- & re-polarization also ® 2-4 Hz
			a. reduced Ca++ influx
				i. [Cl-]i lower  
			b.  reduced efflux through fast-delayed rectifier K+ channels
				i. enhanced activity of IBTX-K+ channels
				                    (iberiotoxin sensitive)
					(1) Ca++ activated   
		3.   Evening Light - entrainment  retinal ganglion cells  RHT 

			a. RHT  Glu  AMPA/NMDA-R on SCN core VIP neurons
			b.  Ca++ influx  NOS + CamK2
				i. NMDAR, T-channels, intracellular ryanodine-R (RyR).  

			c.  pERK  transcription factors  Per1 gene expression

				i.  soluble cytoplasmic factors
					a. CLOCK, BMAL1, PER, CRY, CK1e proteins?

			d. PACAP  AC/cAMP/PKA  pCREB  CRE  Per1 expression
			          Glu release 

			e. Glu  core neuron action potentential  VIP/GRP in SCN shell
				i. NOS  NO  activity of surrounding cells
				ii. GABA signals synchronize SCN neurons
				iii. cascades of "clock" gene expression first in SCN core 
				      spreading into the shell
			f. phase shifts rhythm by maintaining 8-10 Hz rhythm 
			   longer into the day
		4. Darkness  RGC  SCN core shell GABAA  PVN  MFB through SPVZ  
		    Spinal Cord latHorn sympathetic motor neurons  SCG  NE  b2  Pineal 
		    Melatonin  blood  feedback phase-shifts SCN
			a. SCN  timing of Pineal melatonin synthesis and release
				i. melatonin  temporal info to peripheral systems
					(1) but also to SCN
			b. greatest feedback sensitivity at dusk

			c. melatonin  MT1 receptor  outward K+ current 
			    TEAK+ hyperpolarizes SCN neurons  discharge
				i. melatonin desensitizes MT2  PKC
			d. protects initiation time of 2-4 Hz rhythm from RHT entrainment
				i. or initiates earlier 2-4 Hz rhythm
		5. Retina  optic nerve  IGL  GHT  GABA/NPY  SCN shell  HGT

			a. GABAA  SCN firing rate when necessary 
			b. NPY  Y5 receptor  cAMP  NMDA phase shift
			c. blocks VIP terminal output on AVP neurons in shell
			d. to balance photic & non-photic information
				i. stimuli  cellular discharge  non-photic phase-resetting
				   exciting cells produces photic-type phase shifting
		6. IGL  mRaph  5-HT  SCN core 5-HT1B 
			a. presynaptic inhibition of Glu & GABA release involve 5-HT1B-R 
			b. Stimulation of Glu release involve 5-HT7-R
				i. blocks GABAA effect  delays onset of 2-4 Hz rhythm
	C. During the day - fast action potential discharge
		1. soluble cytoplasmic factors suppress TEA-K+ channels 
			a. [Cl-]i higher
		2. Faster de- then re-polariaztion
			a. Enhanced L-type Ca++ currents
			b. K+ currents through fast delayed rectifier channels 
			c. promote rapid action potential upswing and repolarization
	D. Actual behavior is rhythmically modulated in tune with multiple environmental events
		1. \ multiple sensory modality inputs
		2. Locomotor Activity must be coordinated with:
			a. sleep/wake cycles
				i. light, proprioception
			b. body temperature cycles
				i. tactile
				ii. Tob & sleep/wake cycles can move out of phase
			c. eating/energy cycles
				i. tactile
			d. cycles of affect
	E. Multiple sensory zeitgeibers require coordination - SCN Efferents
		1. SCN Master Clock coordinates Multiple Oscillators
			a. coupled circadian oscillators (core + shell)
			   pacemaking via a neuronal network
				i. Maintenance of circadian functioning does not 
				   require an intact neuronal network
				ii. entrainment does
		2. retina, thalamus, hypothalamus, retrochiasmatic area, pineal, habenula,
		   pituitary, kidney, reproductive organs, endocrine glands,
		   have "clock" gene oscillators with weaker rhythmic signals 
		   in the absence of SCN
			a. Hypothalamic generation and integration of rhythms are modulated by
			   AVP, somatostatin (intrinsic to SCN), VIP, enkephalin, substance P(retinal fibers), 
			   NPY, Glu, GABA, 5-HT...
		3. SCN shell  SPVZ  DMH
		   SCN shell  POA
			a. AVP/Glu  reset sleep/wake cycle
				i. stimulates "clock" gene  per
				ii. cell produces VIP, cardiotrophin-like cytokine and prokineticin 2
					(1) paracrines
			b. GABA  resets cycle in opposite direction