Oxytocin Receptors in the Mouse Centrally-projecting Edinger-Westphal Nucleus and their Potential Functional Significance for Thermoregulation

Neuroscience. 2022 Aug 21:498:93-104. doi: 10.1016/j.neuroscience.2022.07.002. Epub 2022 Jul 6.

Abstract

The centrally-projecting Edinger-Westphal nucleus (EWcp) has been shown to contribute to regulation of multiple functions, including responses to stress and fear, attention, food consumption, addiction, body temperature and maternal behaviors. However, receptors involved in regulation of these behaviors through EWcp remain poorly characterized. On the other hand, the oxytocin peptide (OXT) is also known to regulate a substantial number of physiological responses and behaviors. Here we show that mRNA encoding OXT receptors (Oxtr) is expressed in EWcp of male and female C57BL/6J mice. These receptors are present on urocortin 1 (Ucn) mRNA-containing neurons and, to a lesser extent, on neurons in EWcp expressing the vesicular glutamate transporter 2 (Vglut2) mRNA of EWcp. Using RNAscope in situ hybridization, we show that neurons containing Ucn and Vglut2 mRNAs are two intermingled, but independent subpopulations in EWcp and characterize their relationship with other populations of neurons in the vicinity of this nucleus. Using immunohistochemistry, we show that intraperitoneal (IP) administration of OXT can induce FOS in Oxtr-containing neurons, suggesting that these receptors on EWcp neurons are functional. A follow up study showed that injection of OXT (2.3 or 7.7 mg/kg, IP) is accompanied by a decrease in body temperature. Since EWcp is known to be involved in regulation of body temperature, we hypothesize that OXT's effects on body temperature could be mediated through the EWcp. The contribution of OXTR in EWcp to regulation of various functions of EWcp and OXT needs to be deciphered.

Keywords: Edinger-Westphal nucleus; Glutamate; Hypothermia; Oxytocin; Urocortin; c-Fos.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Body Temperature Regulation* / physiology
  • Edinger-Westphal Nucleus* / metabolism
  • Female
  • Follow-Up Studies
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxytocin
  • RNA, Messenger
  • Receptors, Oxytocin* / metabolism
  • Urocortins

Substances

  • RNA, Messenger
  • Receptors, Oxytocin
  • Urocortins
  • Oxytocin