Much is known about the neural circuits of conditioned fear and its relevance to understanding anxiety disorders, but less is known about other anxiety-related behaviors such as active avoidance. Using a tone-signaled, platform-mediated active avoidance task, we observed that pharmacological inactivation of the prelimbic prefrontal cortex (PL) delayed initiation of avoidance. However, optogenetic silencing of PL neurons did not delay avoidance. Consistent with this finding, inhibitory, but not excitatory, responses of rostral PL neurons to the tone were correlated with initiation of avoidance. To oppose inhibitory responses, we photoactivated rostral PL neurons during the tone to maintain pre-tone firing rate. Photoactivation of rostral PL (but not caudal PL) neurons at 4 Hz (but not 2 Hz) delayed or prevented avoidance. These findings suggest that the initiation of active avoidance requires inhibitory neuronal responses in rostral PL, and underscores the importance of designing behavioral optogenetic studies based on neuronal firing patterns.

Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex