Wegner, S, Belle, MDC, Chang, PS, Hughes, ATL, Conibear, AE, Muir, C, Samuels, RE and Piggins, HD (2024) Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability. European Journal of Neuroscience, 60 (11). pp. 6617-6633. ISSN 0953-816X

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Abstract

Individual neurons of the hypothalamic suprachiasmatic nuclei (SCN) contain an intracellular molecular clock that drives these neurons to exhibit day-night variation in excitability. The neuropeptide vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are synthesized by SCN neurons and this intercellular VIP-VPAC2 receptor signal facilitates coordination of SCN neuronal activity and timekeeping. How the loss of VPAC2 receptor signalling affects the electrophysiological properties and states of SCN neurons as well as their responses to excitatory inputs is unclear. Here we used patch-clamp electrophysiology and made recordings of SCN neurons in brain slices prepared from transgenic animals that do not express VPAC2 receptors (Vipr2−/− mice) as well as animals that do (Vipr2+/+ mice). We report that while Vipr2+/+ neurons exhibit coordinated day-night variation in their electrical state, Vipr2−/− neurons lack this and instead manifest a range of states during both day and night. Further, at the population level, Vipr2+/+ neurons vary the membrane threshold potential at which they start to fire action potentials from day to night, while Vipr2−/− neurons do not. We provide evidence that Vipr2−/− neurons lack a component of voltage-gated sodium currents that contribute to SCN neuronal excitability. Moreover, we determine that this aberrant temporal control of neuronal state and excitability alters neuronal responses to a neurochemical mimic of the light-input pathway to the SCN. These results highlight the critical role VIP-VPAC2 receptor signalling plays in the temporal expression of individual neuronal states as well as appropriate ensemble activity and input gating of the SCN neural network.

Item Type:	Article
Uncontrolled Keywords:	AMPA; SCN; VPAC2 receptor; circadian; gating; neurophysiology; sodium current; vasoactive intestinal polypeptide; Animals; Receptors, Vasoactive Intestinal Peptide, Type II; Mice; Circadian Rhythm; Signal Transduction; Suprachiasmatic Nucleus Neurons; Vasoactive Intestinal Peptide; Action Potentials; Male; Suprachiasmatic Nucleus; Mice, Knockout; Mice, Transgenic; Neurons; Mice, Inbred C57BL; Neurosciences; 1.1 Normal biological development and functioning; Neurological; 1109 Neurosciences; 1701 Psychology; 1702 Cognitive Sciences; Neurology & Neurosurgery
Subjects:	Q Science > QH Natural history > QH301 Biology
Divisions:	Biological and Environmental Sciences (from Sep 19)
Publisher:	Wiley
SWORD Depositor:	A Symplectic
Date Deposited:	04 Dec 2024 15:18
Last Modified:	04 Dec 2024 15:18
DOI or ID number:	10.1111/ejn.16590
URI:	https://researchonline.ljmu.ac.uk/id/eprint/25039

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