Behavioral Neuroscience, lecture on Integration of Rhythms into Behavior: Activity
USD Department of Biology
Behavioral Neuroscience
Rhythmicity & Behavior
Sensory input for Rhythmicity
Afferent path to the SCN
Circadian Rhythms
SCN outputs Efferent SCN output
Integration of Rhythms into Behavior
Figures of Rhythmicity
Molecular SCN
end  Acronyms/Abbreviations   Syllabus
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  PermRNA  PER TF activity directly  VIP + AVP

				i. Fast acting response, promotes a stonger rhythm

				ii. but... PER TF activity indirectly  VIP or AVP

					1) by PER TF  Bmal and Clock 

						a) slow acting 24h photophase  scotophase response

					2) BMAL/CLOCK heterodimer TF directly  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 (tetraethylammonia) 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