Parallel, Redundant Circuit Organization for Homeostatic Control of Feeding Behavior

• AGRP neuron axon projections reveal multiple brain regions that elicit feeding
• AGRP neurons comprise multiple subpopulations based on axon projection targets
• Leptin receptor-expressing AGRP neurons selectively project outside the hypothalamus
• AGRP neuron projections highlight an interconnected core forebrain feeding circuit

SummaryNeural circuits for essential natural behaviors are shaped by selective pressure to coordinate reliable execution of flexible goal-directed actions. However, the structural and functional organization of survival-oriented circuits is poorly understood due to exceptionally complex neuroanatomy. This is exemplified by AGRP neurons, which are a molecularly defined population that is sufficient to rapidly coordinate voracious food seeking and consumption behaviors. Here, we use cell-type-specific techniques for neural circuit manipulation and projection-specific anatomical analysis to examine the organization of this critical homeostatic circuit that regulates feeding. We show that AGRP neuronal circuits use a segregated, parallel, and redundant output configuration. AGRP neuron axon projections that target different brain regions originate from distinct subpopulations, several of which are sufficient to independently evoke feeding. The concerted anatomical and functional analysis of AGRP neuron projection populations reveals a constellation of core forebrain nodes, which are part of an extended circuit that mediates feeding behavior.

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