Proceedings of The Physiological Society

Sleep Sleep and Circadian Rhythms (London, UK) (2018) Proc Physiol Soc 42, C07

Poster Communications

Circadian control of paraventricular hypothalamic activity by suprachiasmatic VIP neurons

S. Paul1, L. Walmsley1, C. Harding1, T. Brown1

1. Faculty of Medicine, Biology & Health, University of Manchester, Manchester, United Kingdom.

The co-ordination of our internal physiological rhythms with external time relies on the suprachiasmatic nucleus (SCN) of the hypothalamus. This entrainment with the environment allows organisms to optimise their physiology according to the predictable changes that occur across the 24 hour day. While it is known that the SCN is necessary for this process, the precise nature of the timing signals supplied by the SCN remains unclear. One hypothesis is that the heterogeneity within this small nucleus may allow for the co-ordination of whole body physiology, with subsets of SCN neurons possessing unique circadian profiles that direct specific physiological processes. We tested this hypothesis using optogenetic manipulations of vasoactive intestinal polypeptide (VIP) neurons in the mouse SCN using selective channel rhodopsin-driven manipulation of VIP cells in the mouse SCN while monitoring hypothalamic network activity. Acute ex vivo brain slices were obtained following cervical dislocation, and continuously perfused with aCSF. Recordings were made on both multielectrode arrays, and with penetrating Buszaki-style octodes. These approaches allowed us identify SCN VIP cells, characterise their daily electrophysiological output profiles and also determine how the spike output from these cells influenced neuronal activity in known SCN target regions such as the sub paraventricular zone (SPZ), the paraventricular nucleus of the hypothalamus (PVN), and the ventral thalamus. We identify a subset of cells (~10% of total; n=60) across these SCN target regions that respond to VIP cell activation with robust inhibitions (VIPin+ cells; 50-200ms). Pharmacological challenge reveals that this involves a GABAergic mechanism, since responses are eliminated by application of bicuculline. VIPin+ cells can be found throughout the SPZ, PVN and ventral thalamus. The majority of VIPin+ cells (~80%) show evidence of circadian modulation of firing activity and, collectively, VIPin+ cell activity is lowest during the mid-late afternoon to early night (ZT 5-12). This relative absence of firing corresponds to peak firing phase for SCN VIP cells (~ZT6). Taken together, results from our electrophysiological studies therefore suggest that SCN VIP cells drive rhythmic activity in a subset of responsive downstream neurons in the SPZ, PVN and ventral thalamus. These VIPin+ cells are located in output areas crucial for the control of physiological rhythms, such as the daily rise in corticosterone. These data therefore establish a route by which electrophysiological output from a defined population of SCN neurons could influence a range of downstream physiological rhythms.

Where applicable, experiments conform with Society ethical requirements