The parasubthalamic nucleus refeeding ensemble delays feeding initiation

Abstract

The parasubthalamic nucleus (PSTN) is responsive to refeeding after food deprivation and PSTN subpopulations can suppress feeding. However, no study directly addressed the role of PSTN neurons activated upon food access resumption. Here we show that the ensemble of refeeding-activated PSTN neurons massively increases the latency to initiate refeeding with both familiar and novel food but exerts limited control over the amount of food consumed by hungry mice. This ensemble also delays sucrose consumption but accelerates water consumption in thirsty mice. We next sought to identify which subpopulations of PSTN neurons might be driving these effects. We discovered that PSTN Tac1 neurons projecting to the CeA selectively suppress feeding initiation while PSTN Crh neurons surprisingly promote the consumption of novel, palatable substances. Our results demonstrate the key role of endogenous PSTN activity in the control of feeding initiation and identify PSTN subpopulations counteracting each others influence on consummatory behaviors.

Mouse parasubthalamicCrhneurons drive alcohol drinking escalation and behavioral disinhibition

“…It becomes activated upon sudden food ingestion, exposure to aversive stimuli that reduce feeding (e.g., visceral malaise, novelty, predator odor), and administration of anorectic hormones, thus encoding states of satiety and food rejection. The functional manipulation of PSTN glutamatergic neurons as a whole or subsets of PSTN neurons (e.g., those expressing Tac1 or Adcyap1) demonstrated that their activation serves to suppress food or sucrose intake (40,43,44,(48)(49)(50)(51). Consistent with prior literature, chemogenetic activation of PSTN Tac1 neurons virtually ablated the consumption of alcohol and saccharin in our experimental conditions.…”

“…Accordingly, while it is possible that the small subset of PSTN neurons co-expressing Crh and Tac1 promotes alcohol intake via NK1 signaling, the activity of PSTN Tac1 neurons as a whole inhibits alcohol drinking. This inhibitory influence of PSTN Tac1 neurons extends to saccharin drinking and is consistent with the general pattern of feeding/drinking suppression previously reported for this population (40,43,44).…”

“…In this context, our finding that PSTN Crh neurons promote the consumption of alcohol and saccharine sets these neurons apart as a unique subset opposing the influence of neighboring populations. In a recent study, we found that activating PSTN Crh neurons promotes the consumption of a novel, palatable food (Froot Loops) in hungry mice, and the consumption of a novel, palatable fluid (sucrose) in thirsty mice (44). Here, we show that this effect extends to alcohol and saccharin drinking, does not require fluid deprivation, and withstands the concomitant availability of water (free-choice consumption) and extensive habituation to the reinforcers.…”