Orexin A excites the rat olivary pretectal nucleus via OX2 receptor in a daily manner

Abstract

Pronounced environmental changes between the day and night forced living organisms to evolve specialised mechanisms organising their daily physiology, named circadian clocks. Currently, it has become clear that the master clock in the suprachiasmatic nuclei of the hypothalamus is not an exclusive brain site to generate daily rhythms. Indeed, several brain areas, including the subcortical visual system have been recently shown to change their neuronal activity across the daily cycle. Here we focus our investigation on the olivary pretectal nucleus (OPN) - a retinorecipient structure primarily involved in the pupillary light reflex. Using the multi-electrode array technology ex vivo we provide evidence for OPN neurons to elevate their firing during the behaviourally quiescent light phase. Additionally, we report the robust sensitivity to orexin A via the identified OX2 receptor in this pretectal centre, with higher responsiveness noted during the night. Interestingly, we likewise report a daily variation in the response to PAC1 receptor activation, with implications for the convergence of orexinergic and visual input on the same OPN neurons. Altogether, our report is first to suggest a daily modulation of the OPN activity via intrinsic and extrinsic mechanisms, organising its temporal physiology. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/443625v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@97ec8eorg.highwire.dtl.DTLVardef@2b5eeforg.highwire.dtl.DTLVardef@165d985org.highwire.dtl.DTLVardef@1abb7c9_HPS_FORMAT_FIGEXP M_FIG C_FIG HIGHLIGHTSO_LINeurons in the olivary pretectal nucleus (OPN) increase their firing during the day C_LIO_LIOrexin A robustly excites the OPN via the OX2 receptor C_LIO_LIOrexin A and the activation of PAC1 receptor are more effective during the night C_LI