SCN ( supra chiasmatic nucleus)

MASTER CIRCADIAN PACEMAKER in mammals.

1. SCN ( SUPRA CHIASMATIC NUCLEUS) SUBMITTED TO DEPARTMENT OF ZOOLOGY ISABELLA THOBURN COLLEGE LUCKNOW

2. INTRODUCTION The supra chiasmatic nucleus or nuclei (SCN) is a tiny region of brain in the hypothalamus as the site of the MASTER CIRCADIAN PACEMAKER in mammals. Responsible for controlling circadian rhythms, regulate many different body functions in a 24 hour cycle. Phase shift of the SCN pacemaker activity can be induced by light exposure, the direction and magnitude of phase shift.

3. LIGHT PULSES LIGHT PULSES LIGHT PULSES During the subjective day (circadian time CT 0-12) Have little effect During the start of subjective night (CT 12-14) Will delay the clock At the end of subjective night (CT 18-24) Will advance the clock SCN cells may not require direct neural connection to control circadian rhythms, but may do using chemical signals.

4. VISUAL PROPERTIES OF SCN visual SCN neurons responded to retinal illumination with a sustained increase or a sustained decrease in electrical discharge . The majority (75%) of these cells were activated by light . In both the rat and the hamster SCN, visually responsive cells altered their discharge rate as a monotonic function of luminance. The spontaneous firing rates as well as the responsiveness of visual SCN cells were subject to marked variations between and within cells . This property makes these cells suitable to mediate photic entrainment of circadian rhythms as well as the measurement of photoperiod.

5. TYPES OF SCN CELLS Light activated SCN cells Light suppressed SCN cells Both cells respond to long duration light. When an animal is exposed to increasing light intensities Increases their discharge rate at certain level of illumination. Resulting in no response with a further increment in discharge rate. Decrease their spontaneous discharge rate. Increase illumination.

6. ANATOMY AND PHYSIOLOGY OF SCN Cellular organisation of the SCN Neuropeptide and neurotransmitter contents of SCN Input pathway to the SCN Output pathway of SCN Significance of peptides

7. ANATOMY OF SCN CELLULAR ORGANISATION OF SCN

8. CELLULAR ORGANISATION OF THE SCN SCN is a paired nucleus localised adjacent to the third ventricle and on the top of the optic chiasma. In rat SCN about 16,000 small and tightly packed neurons are present. There are two parts of SCN based on morphological differences. Small rostral area Large caudal area Shell (dorsomedial part) Core (Ventrolateral part)

9. SHELL It is the dorsomedial part of the caudal SCN (dmSCN). Characterised by small elongated neuron with large nuclei and few cell organelles. CORE It is the ventrolateral part of caudal SCN (vlSCN). Characterised by lower density of spherical neurons which have organelle rich cytoplasm. in the SCN, complex synaptic arrangement have been found with axo-sometic contents as well as dendro –dendritic oppositions. Large region of cell-cell oppositions and small extracellular volume in the SCN changes the composition of extracellular fluid can alter the firing of the SCN neurons.

10. Neuropeptide and neurotransmitter content of SCN Gama aminobutyric acid vasopressin Vasoactive intestinal polypeptide Gastrin releasing peptide somatostatin

11. Gama amino butyric acid (GABA) GABA and GABA receptors are abundantly present in SCN, and plays important role. Level of m RNA of glutamic acid decarboxylase (GAD)(the enzyme converting glutamate into GABA) shows circadian rhythm in the SCN. Both GABA level and GAD activity shows a circadian fluctuation under LD and DD condition in SCN. Vasopressin (VP) Its precise role in SCN is still unclear. VP levels and VP m RNA levels cycle in the SCN under both LD and DD condition with peak level during the L-phase of the circadian rhythm. Vasoactive intestinal polypeptide (VIP) Levels of VIP m RNA and proteins show a diurnal rhythm in SCN neurons under LD conditions with peak level during night. Under DD condition it remain constant. The VIP is not necessary to convey the rhythmic signals of the SCN to target areas.

12. EXPRESSION PATTERN OF VP m RNA AND PEPTIDE IN THE MAMMALIAN SCN Dark bars night time Brown bars period of presence of the short form of VP m-RNA poly (A) tail.

13. Gastrin realising peptide (GRP) Levels of GRP, which is found to be co-localized with VIP in the VISCN. Shows diurnal rhythm under LD condition, which is 12 hours out of phase with the VIPO rhythm. The ratio of VIPO to GRP available for release from SCN neurons thus varies over the day-night cycle, act as a timing signal. VIP and GRP neurons also project outside the SCN, the ratio of these peptides communicate information about the LD cycle to area outside the SCN. Somatostatin (SOM) The circadian expression of SOM in the SCN during LD remains present under DD condition. SOM marks a separate group of cells located in ventral aspects of dmSCN. The high degree of connectivity with other SCN neurons suggest an important role.

14. INPUT PATHWAY TO THE SCN PHOTIC PHASE SHIFT NON-PHOTIC PHASE SHIFT Light is the main entraining factor of the SCN. The signalling pathways from the retina to SCN comprises the activation of photoreceptor in the retina and a glutamate release in the SCN from terminals of RHT. Light induced phase shifts are marked by an induction of immediate early gene (IEG) expression. A specific role for C- fos m-RNA induction in the phase shifting effect of light was inferred from its localisation in the retinorecipient area of the SCN. PHOTIC PHASE SHIFT

15. NON-PHOTIC PHASE SHIFT An increase in the activity level of a natural animal during its inactive period, for instance by a dark pulse, forced wheel running or a benzodiazepine injection , results a large phase advance. A common structure involved in the non photic phase shifts appears to be the IGL, with NPY as the main neurotransmitter acting in SCN. The mechanism of phase shifting by a non photic stimulus is largely unknown. Non photic stimulation neither effect C AMP Response Element Binding Protein (CREB) phosphorylation.

16. OUTPUT PATHWAY OF THE SCN The circadian rhythm, generated in SCN is imposed on many physiological function, including body temperature, locomotor activity sleep, water and food intake, pineal melatonin synthesis and receptor densities. The circadian rhythm of VP level in CSF is not likely to act as a limiting signals for the brain. The most prominent projection from the rat and hamster SCN run dorsally and ends in the subparaventricular zone (PVN) with a small portion of fibres.

17. INPUT AND OUTPUT PATHWAY OF THE SCN

18. NEURAL PROJECTION OF SCN AFFERENT EFFERENT IDENTIFICATION OF NEURAL AFFERENT The SCN receives several afferents from the retina. Two neural projection reach SCN . RETINOHYPOTHALAMIC TRACT (RHT) GENICULOHYPOTHALAMIC TRACT (GHT)

19. NEURAL PROJECTION OF SCN

20. Retinohypothalamic tract (RHT) Direct bilateral pathway that leaves the optic chiasm dorsally to terminate with fine unmylinated fibres along the ventrolateral aspects of SCN. Eg. In the hamster, the terminals also end more dorsally, laterally and caudally form the SCN. Involves a retinofungal projection to the ventral lateral geniculate nucleus (VlGN) and the integeniculate leaflet (IGL). A subpopulation of neuropeptide gama (NPY)- immunoreactive VlGN and IGL perikarya in turn send axons to the SCN. Geniculohypothalamic tract (GHT)

21. EFFERENT OF SCN The SCN drive a great number of behavioural and physiological rhythms. SCN lesions affect the rhythmicity in locomotor activity, food intake, as well as deep body temperature and sleep wakefulness cycle. The involvement of neuronal pathway in the control of these functions become evident as effect of SCN lesions can be mimicked by surgical isolation of the SCN. These process also indicate neuronal control of these rhythms.

22. SIGNIFICANCE OF SCN SCN plays a central role in the daily programming of organismic functions by regulating day to day oscillation and synchronizing them to changing cycle of day and night. GHT is significant for visual response of the SCN and for circadian rhythmicity in locomotor activity. RHT is significant for ongoing e ntrainment by lesioning the geniculate neurons. This biological clock drives the daily expression of vital homeostasis functions.

23. THANK YOU…..