The parasubthalamic nucleus refeeding ensemble delays feeding initiation and hastens water drinking.

Abstract

The parasubthalamic nucleus (PSTN) is activated by refeeding after food deprivation and several PSTN subpopulations have been shown to suppress feeding. However, no study to date directly addressed the role of PSTN neurons activated upon food access in the control of ensuing food consumption. Here we identify consumption latency as a sensitive behavioral indicator of PSTN activity, and show that, in hungry mice, the ensemble of refeeding-activated PSTN neurons drastically increases the latency to initiate refeeding with both familiar and a novel, familiar food, but does not control the amount of food consumed. In thirsty mice, this ensemble also delays sucrose consumption but accelerates water consumption, possibly reflecting anticipatory prandial thirst, with again no influence on the amount of fluid consumed. We next sought to identify which subpopulations of PSTN neurons might be driving these latency effects, using cell-type and pathway-specific chemogenetic manipulations. Our results suggest a prominent role of PSTN Tac1 neurons projecting to the central amygdala in the hindrance of feeding initiation. While PSTN Crh neurons also delay the latency of hungry mice to ingest familiar foods, they surprisingly promote the consumption of novel, palatable substances. Furthermore, PSTN Crh neurons projecting to the bed nucleus of the stria terminalis accelerate rehydration in thirsty mice. Our results demonstrate the key role of endogenous PSTN activity in the control of feeding and drinking initiation and delineate specific circuits mediating these effects, which may have relevance for eating disorders.