DOPAMINERGIC ACTIVITY ACROSS DIFFERENT CORTICO-STRIATO-THALAMO-<WBR>CORTICAL PATHWAYS DURING COMPULSIVE-LIKE GROOMING BEHAVIOR IN FREELY MOVING MICE

Obsessive Compulsive Disorder (OCD) is characterized by compulsive behaviors and has been associated with dysregulation of dopaminergic signaling within cortico-striato-thalamo-cortical (CSTC) circuits. This work characterizes and compares dopaminergic activity patterns across distinct CSTC pathways during grooming in regular C-57 blacks control mice and Sapap3-knockout, a mouse model of OCD with excessive grooming behavior phenotype. We compare the dopamine (DA) activity in the three major DA tracts of the CSTC circuits: The Mesolimbic pathway from the ventral tegmental area to the ventral striatum (VTA–VS), the medial nigrostriatal pathway from the substantia nigra pars compacta to the dorsomedial striatum (SNc–DMS) and the lateral nigrostriatal pathway from the SNc to the dorsolateral striatum (SNc–DLS). Optogenetic tagging and electrophysiological recordings are used to characterize pathway-specific dopaminergic activity during spontaneous grooming behavior. Grooming behavior is quantified by using the unsupervised machine-learning algorithm B-SOiD, which enables high-temporal-resolution classification of grooming subtypes and kinematics features. This approach allows us to characterize pathway-specific dopaminergic activity across CSTC-related pathways during grooming and differentiate maladaptive grooming in the OCD-model mice from grooming in control animals. Therefore, this work may offer an insight into the involvement of DA in the circuit-level mechanisms underlying compulsive-like behavior.