An Insula-Central Amygdala Circuit for Guiding Tastant-Reinforced Choice Behavior

For animals to survive, they must reliably predict during foraging which substances are suitable for consumption. Despite extensive study, the neural circuit mechanisms underlying such adaptive behavior remain poorly understood. Here, using a tastant (sucrose/quinine)-reinforced "go/no-go" task in male and female mice, we examined the anatomical and functional connectivity of the circuit linking the insular cortex (IC) to the central amygdala (CeA) and the role of this circuit in the establishment of appropriate behavioral responses. Using anatomic tracing approaches combined with optogenetics-assisted circuit mapping, we found that the gustatory region of the IC sends direct excitatory projections to the lateral division of the CeA (CeL), making monosynaptic excitatory connections with distinct populations of CeL neurons. Specific inhibition of neurotransmitter release from the CeL-projecting IC neurons prevented mice from acquiring the "no-go" response, and impaired the "go" responses in the go/no-go task. Furthermore, selective activation of the IC-CeL pathway with optogenetics drove unconditioned lick suppression in thirsty animals, induced aversive responses, and was sufficient to instruct conditioned action suppression in response to a cue predicting the optogenetic activation. These results indicate that activities in the IC-CeL circuit are critical for establishing taste-reinforced behavioral responses, including avoidance responses to an aversive tastant, and are sufficient to drive learning of anticipatory avoidance. Our findings suggest that the IC-CeL circuit plays an important role in guiding appropriate choices during foraging.SIGNIFICANCE STATEMENT An animal's ability to predict which substances are suitable for consumption and then produce an appropriate action to those substances is critical for survival. Here we found that activity in the circuit that links the insular cortex (IC) to the central amygdala (CeA) is necessary for establishing appropriate behavioral responses to taste-predicting cues. This neural circuit seems to be particularly tuned to avoid an unpleasant tastant, and is also sufficient to drive learning of such avoidance responses. These results suggest that the IC-CeA circuit is critical for generating appropriate behavioral responses during foraging when facing different choices.