A phosphate transporter in VIPergic neurons of the suprachiasmatic nucleus gates locomotor activity during the light/dark transition in mice

Sara Pierre-Ferrer; Ben Collins; David Lukacsovich; Shao'Ang Wen; Yuchen Cai; Jochen Winterer; Jun Yan; Lene Pedersen; Csaba Földy; Steven A Brown

doi:10.1016/j.celrep.2024.114220

A phosphate transporter in VIPergic neurons of the suprachiasmatic nucleus gates locomotor activity during the light/dark transition in mice

Cell Rep. 2024 May 11;43(5):114220. doi: 10.1016/j.celrep.2024.114220. Online ahead of print.

Authors

Affiliations

¹ Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address: sara.pierreferrer@gmail.com.
² Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Department of Biology, Sacred Heart University, 5151 Park Ave., Fairfield, CT 06825, USA.
³ Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
⁴ Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
⁵ Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus, Denmark.
⁶ Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. Electronic address: foldy@hifo.uzh.ch.
⁷ Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.

PMID: 38735047
DOI: 10.1016/j.celrep.2024.114220

Abstract

The suprachiasmatic nucleus (SCN) encodes time of day through changes in daily firing; however, the molecular mechanisms by which the SCN times behavior are not fully understood. To identify factors that could encode day/night differences in activity, we combine patch-clamp recordings and single-cell sequencing of individual SCN neurons in mice. We identify PiT2, a phosphate transporter, as being upregulated in a population of Vip⁺Nms⁺ SCN neurons at night. Although nocturnal and typically showing a peak of activity at lights off, mice lacking PiT2 (PiT2^-/-) do not reach the activity level seen in wild-type mice during the light/dark transition. PiT2 loss leads to increased SCN neuronal firing and broad changes in SCN protein phosphorylation. PiT2^-/- mice display a deficit in seasonal entrainment when moving from a simulated short summer to longer winter nights. This suggests that PiT2 is responsible for timing activity and is a driver of SCN plasticity allowing seasonal entrainment.

Keywords: CP: Neuroscience; PiT2; SCN; Slc20a2; VIP; circadian; phosphoproteome; single-cell sequencing; suprachiasmatic nucleus; vasointestinal polypeptide; winter seasonality.