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 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. However, 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 while the NAc encodes avoidance movements, it is not required for avoidance behaviors, highlighting the distinction between behavior encoding or representation and mediation or generation.

Significance statement Adaptive avoidance behaviors are used by animals, including humans, to avert danger in the environment. For example, humans use signaled avoidance strategies to cross the street at a crosswalk. This study sheds light on the role of an area in the forebrain called the nucleus accumbens (NAc) purported to be important for adaptive avoidance behaviors. The findings show that like many other areas NAc is engaged during these behaviors but is not required to generate them. The results open new avenues for understanding the neural basis of adaptive avoidance behaviors and the functional role of NAc.