Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes obsessive-compulsive disorder-like behaviors in mice

Abstract

Abstract Obsessive compulsive disorder (OCD) is a debilitating neuropsychiatric condition characterized by obsessions and compulsions. Despite the crucial role of the amygdala in anxiety, its role in OCD remains unclear. We found that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of OCD-related behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor. Specific optogenetic activation of the BLA-DMS circuit induced a strong anxiety response followed by compulsive grooming. Furthermore, we developed a mouse OCD model displaying a wide spectrum of OCD-like behaviors by chronically activating the BLA-DMS circuit. In these mice, persistent molecular changes at the BLA-DMS synapses observed were causally related to the OCD-like phenotypes. Together, our study demonstrates the involvement of the BLA-DMS circuit in the emergence of enduring OCD-like compulsive behaviors via its persistent synaptic changes.