Parasubthalamic calretinin neurons modulate wakefulness associated with exploration in male mice

The parasubthalamic nucleus (PSTN) is considered to be involved in motivation, feeding and hunting, all of which are highly depending on wakefulness. However, the roles and underlying neural circuits of the PSTN in wakefulness remain unclear. Neurons expressing calretinin (CR) account for the majority of PSTN neurons. In this study in male mice, fiber photometry recordings showed that the activity of PSTN CR neurons increased at the transitions from non-rapid eye movement (non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior. Chemogenetic and optogenetic experiments demonstrated that PSTN CR neurons were necessary for initiating and/or maintaining arousal associated with exploration. Photoactivation of projections of PSTN CR neurons revealed that they regulated exploration-related wakefulness by innervating the ventral tegmental area. Collectively, our findings indicate that PSTN CR circuitry is essential for the induction and maintenance of the awake state associated with exploration. The neural circuits regulating wakefulness have not been fully resolved. Here, the authors reveal that neurons expressing calretinin in the parasubthalamic nucleus play a key role in the induction and maintenance of the awake state associated with exploration via projections to the ventral tegmental area.