Abstract: The needs of the body can direct behavioral and neural processing towards motivationally relevant sensory cues. For example, human neuroimaging studies have consistently found specific cortical areas with biased responses to food-associated visual cues in hungry subjects, but not in sated subjects. To obtain a cellular-level understanding of these hunger-dependent cortical response biases, we performed chronic two-photon calcium imaging in insular cortex (InsCtx), postrhinal association cortex (POR), and primary visual cortex (V1) of behaving mice. As in humans, neurons in mouse InsCtx and POR, but not V1, exhibited biases towards food-associated cues that were abolished by satiety. These emergent biases were mirrored by the innervation pattern and hunger-dependent food cue responses in amygdalo-cortical feedback axons. Surprisingly, we found that chemogenetic activation of hypothalamic AgRP neurons (sensors of caloric deficit, whose activation induces feeding) in sated mice restored food cue-biased neuronal population responses in InsCtx. Using AgRP neurons as a genetic entry-point for circuit mapping, we then uncovered a pathway linking AgRP neurons to basolateral amygdala and InsCtx. Our findings provide a framework for understanding how a circuit underlying a specific motivational drive can selectively bias sensory cortical processing towards motivationally-relevant cues.
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