A discrete parasubthalamic nucleus subpopulation plays a critical role in appetite suppression

Abstract

Food intake behavior is regulated by a network of appetite-inducing and appetite-suppressing neuronal populations throughout the brain. The parasubthalamic nucleus (PSTN), a relatively unexplored population of neurons in the posterior hypothalamus, has been hypothesized to regulate appetite due to its connectivity with other anorexigenic neuronal populations and because these neurons express Fos, a marker of neuronal activation, following a meal. However, the individual cell types that make up the PSTN are not well characterized, nor are their functional roles in food intake behavior. Here we identify and distinguish between two discrete PSTN subpopulations, those that express tachykinin-1 (PSTNTac1 neurons) and those that express corticotropin-releasing hormone (PSTNCRH neurons), and use a panel of genetically encoded tools in mice to show that PSTNTac1 neurons play an important role in appetite suppression. Both subpopulations increase activity following a meal and in response to administration of the anorexigenic hormones amylin, cholecystokinin (CCK), and peptide YY (PYY). Interestingly, chemogenetic inhibition of PSTNTac1, but not PSTNCRH neurons, reduces the appetite-suppressing effects of these hormones. Consistently, optogenetic and chemogenetic stimulation of PSTNTac1 neurons, but not PSTNCRH neurons, reduces food intake in hungry mice. PSTNTac1 and PSTNCRH neurons project to distinct downstream brain regions, and stimulation of PSTNTac1 projections to individual anorexigenic populations reduces food consumption. Taken together, these results reveal the functional properties and projection patterns of distinct PSTN cell types and demonstrate an anorexigenic role for PSTNTac1 neurons in the hormonal and central regulation of appetite.

Parabrachial-to-parasubthalamic nucleus pathway mediates fear-induced suppression of feeding in male mice

“…Therefore, inhibition of PSTN neurons is insufficient to affect baseline food intake. These findings are consistent with a recent report 33 .…”

“…The PSTN plays a key role in the termination of feeding behaviors 38,39 . A recent paper demonstrated that the PSTN plays a critical role in appetite suppression 33 . Therefore, we examined whether the lPB-PSTN pathway modulates feeding behavior by optogenetically activating the lPB terminals in the PSTN.…”

“…Recent papers demonstrated that the PSTN neurons are involved in appetite suppression 33,40 . Therefore, we next examined the necessity of the lPB-PSTN pathway in feeding suppression.…”

“…The PSTN is located in the lateral subdivision of the posterior hypothalamus 31 . The PSTN recently emerged as a critical interface between interoception and emotions 32 , and for the regulation of appetite suppression 33 . Yet, its physiological roles in health and disease are still largely unexplored.…”

Advances in optogenetic studies of depressive-like behaviors and underlying neural circuit mechanisms

“…Apart from AgRP and POMC neurons, other populations in the hypothalamus also contribute to appetite regulation, including a subset of nucleus of the solitary tract neurons containing cholecystokinin (CCK NTS ) ( 70 ), glutamatergic neurons projecting to PVH in the medial septal complex (MSc) ( 71 ), tachykinin-1 expressing neurons (PSTN Tac1 ) in the parasubthalamic nucleus ( 72 ), steroidogenic factor 1 (SF1) neurons in the ventromedial hypothalamus ( 73 ), and melanin-concentrating hormone-expressing neurons ( 74 ). In addition, progress has also been made in some known appetite-regulating factors like neuropeptide Y (NPY) and orexin with optogenetics ( 75 , 76 ).…”