Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop

Yunlei Yang, Deniz Atasoy, Helen H. Su, Scott M. Sternson

Research output: Contribution to journalArticlepeer-review

264 Scopus citations

Abstract

Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types. Here, we combine cell-type-specific electrophysiological, pharmacological, and optogenetic techniques to dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons, a population that regulates feeding. We find that food deprivation elevates excitatory synaptic input, which is mediated by a presynaptic positive feedback loop involving AMP-activated protein kinase. Potentiation of glutamate release was triggered by the orexigenic hormone ghrelin and exhibited hysteresis, persisting for hours after ghrelin removal. Persistent activity was reversed by the anorexigenic hormone leptin, and optogenetic photostimulation demonstrated involvement of opioid release from POMC neurons. Based on these experiments, we propose a memory storage device for physiological state constructed from bistable synapses that are flipped between two sustained activity states by transient exposure to hormones signaling energy levels.

Original languageEnglish (US)
Pages (from-to)992-1003
Number of pages12
JournalCell
Volume146
Issue number6
DOIs
StatePublished - Sep 16 2011
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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