Flip-flop memory circuit uses a synaptic AMPK-dependent positive feedback loop and is switched by hunger state.

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Appetite. 2011 Jul 01;57(1):47. doi: 10.1016/j.appet.2011.05.296

Flip-flop memory circuit uses a synaptic AMPK-dependent positive feedback loop and is switched by hunger state. Sternson Lab

Yang Y, Atasoy D, Sternson S

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Abstract

Synaptic plasticity in response to changes in physiologic state is coordinated by hormonal signals across multiple neuronal cell types, but the significance and underlying mechanisms are unclear. 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. Supported by: Howard Hughes Medical Institute.

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Flip-flop memory circuit uses a synaptic AMPK-dependent positive feedback loop and is switched by hunger state.

Abstract

Janelia Authors