GABAergic inputs to POMC neurons originating from the dorsomedial hypothalamus are regulated by energy state

Andrew R. Rau, Shane T. Hentges

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Neuronal circuits regulating hunger and satiety synthesize information encoding the energy state of the animal and translate those signals into motivated behaviors to meet homeostatic needs. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus are activated by energy surfeits and inhibited by energy deficits. When activated, these cells inhibit food intake and facilitate weight loss. Conversely, decreased activity in POMC cells is associated with increased food intake and obesity. Circulating nutrients and hormones modulate the activity of POMC neurons over protracted periods of time. However, recent work indicates that calcium activity in POMC cells changes in response to food cues on times scales consistent with the rapid actions of amino acid transmitters. Indeed, the frequency of spontaneous IPSCs (sIPSCs) onto POMC neurons increases during caloric deficits. However, the afferent brain regions responsible for this inhibitory modulation are currently unknown. Here, through the use of brain region-specific deletion of GABA release in both male and female mice we show that neurons in the dorsomedial hypothalamus (DMH) are responsible for the majority of sIPSCs in POMC neurons as well as the fasting-induced increase in sIPSC frequency. Further, the readily releasable pool of GABA vesicles and the release probability of GABA is increased at DMH-to-POMC synapses following an overnight fast. Collectively these data provide evidence that DMH-to-POMC GABA circuitry conveys inhibitory neuromodulation onto POMC cells that is sensitive to the animal’s energy state.

Original languageEnglish
Pages (from-to)6449-6459
Number of pages11
JournalJournal of Neuroscience
Volume39
Issue number33
DOIs
StatePublished - Aug 12 2019

Keywords

  • Arcuate nucleus
  • Calcium imaging
  • Electrophysiology
  • Optogenetic
  • Proopiomelanocortin
  • Synaptic

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