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

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. [Display omitted] • PiT2 expression is upregulated in night-active Vip ⁺ Nms ⁺ SCN neurons • Mice lacking PiT2 show decreased behavioral activity at the light/dark transition • Loss of PiT2 leads to increased SCN neuronal firing and phosphorylation changes in the SCN • Winter seasonality entrainment depends on PiT2 function in SCN neurons Pierre-Ferrer et al. report that the phosphate transporter PiT2 regulates behavior at the light/dark transition in mice by decreasing the firing frequency and modifying the phosphorylation landscape of suprachiasmatic nucleus (SCN) neurons. Furthermore, PiT2 is essential for proper winter seasonality entrainment at the light/dark transition. [ABSTRACT FROM AUTHOR]