Dopamine modulates visual threat processing in the superior colliculus via D2 receptors

Dopamine (DA) system is intriguing in the aspect that distinct, typically opposing physiological functions are mediated by D1 dopamine receptors (Drd1) and D2 dopamine receptors (Drd2). Both Drd1+ and Drd2+ neurons were identified in superior colliculus (SC), a visuomotor integration center known for its role in defensive behaviors to visual threats. We hypothesized that Drd1+ and Drd2+ neurons in the SC may play a role in promoting instinctive defensive responses. Optogenetic activation of Drd2+ neurons, but not Drd1+ neurons, in the SC triggered strong defensive behaviors. Chemogenetic inhibition of SC Drd2+ neurons decreased looming-induced defensive behavior, suggesting involvement of SC Drd2+ neurons in defensive responses. To further confirm this functional role of Drd2 receptors, pretreatment with the Drd2+ agonist quinpirole in the SC impaired looming-evoked defensive responses, suggesting an essential role of Drd2 receptors in the regulation of innate defensive behavior. Inputs and outputs of SC Drd2+ neurons were investigated using viral tracing: SC Drd2+ neurons mainly receive moderate inputs from the Locus Coeruleus (LC), whilst we did not find any incoming projections from other dopaminergic structures. Our results suggest a sophisticated regulatory role of DA and its receptor system in innate defensive behavior.