Prefrontal ErbB4-positive interneurons for avoidance

Avoidance is a major behavior for survival. The prefrontal cortex (PFC) is known to be involved in approach-avoidance decision-making, but how PFC interneurons (INs) collaborate with excitatory neurons in this process remains unclear. Our research reveals that ErbB4⁺ interneurons (B4INs) increased calcium transients in avoidance behaviors of freely moving mice. B4IN inhibition or activation is required for and sufficient to induce avoidance behaviors. B4INs receive monosynaptic inputs from glutamatergic neurons in the basal forebrain (BF), whose activation and suppression induce and inhibit avoidance, respectively. By registering target neurons of B4INs, we show that most avoidance-associated neurons are under the inhibitory control of B4INs, suggesting that B4INs act by suppressing excitatory neurons to mediate avoidance behaviors. Finally, pharmacological inhibition of ErbB4 reduces avoidance behaviors, suggesting that B4IN activity depends on ErbB4 kinase activity. These results reveal a causal role for B4INs in avoidance behaviors.