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
Affiliations
Sara Pierre-Ferrer
Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Corresponding author
Ben Collins
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
David Lukacsovich
Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Shao’Ang Wen
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
Yuchen Cai
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
Jochen Winterer
Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Jun Yan
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
Lene Pedersen
Department of Molecular Biology and Genetics, Aarhus University, Universitetsbyen 81, 8000 Aarhus, Denmark
Csaba Földy
Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland; Corresponding author
Steven A. Brown
Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, Faculties of Medicine and Science, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland
Summary: 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.
