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

Brain Res. 2021 Oct 1:1768:147603. doi: 10.1016/j.brainres.2021.147603. Epub 2021 Jul 29.


Pronounced environmental changes between the day and night led to evolution of 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 responsivity 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.

Keywords: Circadian clock; Electrophysiology; Multi-electrode arrays; Olivary pretectal nucleus; Orexin; PAC1 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Circadian Clocks / physiology
  • Circadian Rhythm / physiology*
  • Male
  • Neurons / physiology
  • Orexin Receptors / metabolism
  • Orexins / metabolism*
  • Pretectal Region / metabolism*
  • Pretectal Region / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / physiology
  • Suprachiasmatic Nucleus / metabolism
  • Vision, Ocular


  • Orexin Receptors
  • Orexins