Role of the nucleus accumbens in signaled avoidance actions

Abstract

Animals, humans included, navigate their environments guided by sensory cues, responding adaptively to potential dangers and rewards. Avoidance behaviors serve as adaptive strategies in the face of signaled threats, but the neural mechanisms orchestrating these behaviors remain elusive. Current circuit models of avoidance behaviors indicate that the nucleus accumbens (NAc) in the ventral striatum plays a key role in signaled avoidance behaviors, but the nature of this engagement is unclear. Evolving perspectives propose the NAc as a pivotal hub for action selection, integrating cognitive and affective information to heighten the efficiency of both appetitive and aversive motivated behaviors. To unravel the engagement of the NAc during active and passive avoidance, we used calcium imaging fiber photometry and single-unit recordings to examine NAc GABAergic neuron activity in freely moving mice performing avoidance behaviors. We then probed the functional significance of NAc neurons using optogenetics, and genetically targeted or electrolytic lesions. We found that NAc neurons code contraversive orienting movements and avoidance actions. Intriguingly, specific optogenetic patterns intended to excite NAc GABAergic neurons resulted in local somatic inhibition through GABAergic synaptic collaterals. Nevertheless, these patterns directly excited NAc GABAergic output axons, which in turn inhibited their targets, disrupting active avoidance behavior. Thus, this disruption stemmed from abnormal alterations in the activity of downstream midbrain areas crucial for the behavior. In contrast, direct optogenetic inhibition or lesions of NAc neurons did not impair active or passive avoidance behaviors, challenging the notion of their purported pivotal role in adaptive avoidance. The findings emphasize that NAc is not required for avoidance behaviors, but disruptions in NAc output during pathological states can impair these behaviors.