Bidirectional control of BLA-DMS and PFC-DMS projections on innate avoidance behaviour in mice.

Avoidance behaviour, aimed at escaping dangerous stimuli and threatening situations, can become maladaptive when individuals avoid relatively safe situations, a hallmark of anxiety disorders. Innate avoidance, a natural aversion to ethologically relevant stimuli, involves a neural circuit in which the basolateral amygdala (BLA) and prefrontal cortex (PFC) play a central role. We have observed that both the PFC and the BLA send converging unidirectional excitatory inputs to the dorsomedial striatum (DMS), which thus may be ideally positioned to regulate the output of this circuit. Indeed, the DMS has been implicated in learned, and more recently in innate avoidance behaviours. To investigate the role of the PFC-DMS and BLA-DMS pathways in innate avoidance, we used a chemogenetic approach. CD1 male mice received a bilateral injection of AAVs expressing either the inhibitory DREADD hM4D(Gi) or the excitatory DREADD hM3D(Gq) in the PFC or BLA. Then, mice were focally injected with CNO or saline into the DMS and tested in the elevated plus maze (EPM) 30 minutes later. Inhibiting the PFC-DMS pathway did not affect the time spent in open arms of the EPM, but its activation significantly reduced anxiety. On the other hand, activation of the BLA-DMS pathway led to a reduction in the time spent in the open arms, while its inhibition had a strong anxiolytic effect. These results not only confirm the involvement of PFC-DMS and BLA-DMS projecting neurons in mice behaviour in the EPM, but also underscore that these pathways exert opposing bidirectional control over innate avoidance.