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

Area of Science:

• Neuroscience
• Molecular Biology
• Endocrinology

Background:

• Hormonal signals coordinate synaptic plasticity across neuronal types in response to physiological changes.
• Agouti-related peptide (AGRP) neurons are key regulators of feeding behavior.

Purpose of the Study:

• To dissect neural circuits and molecular pathways controlling synaptic plasticity onto AGRP neurons.
• To understand how hormones regulate feeding behavior at the synaptic level.

Main Methods:

• Cell-type-specific electrophysiology
• Pharmacological and optogenetic techniques
• Analysis of synaptic plasticity in AGRP neurons

Main Results:

• Food deprivation increases excitatory synaptic input to AGRP neurons via a positive feedback loop involving AMP-activated protein kinase.
• Ghrelin potentiates glutamate release, causing a persistent increase in synaptic activity (hysteresis).
• Leptin reverses this persistent activity, and opioid release from POMC neurons is involved.

Conclusions:

• A novel hormonal memory storage device for physiological state is proposed, utilizing bistable synapses.
• Synaptic plasticity in AGRP neurons is dynamically regulated by hormones signaling energy levels.
• This mechanism provides insight into how the brain maintains physiological state memory.