CHARACTERIZING DOPAMINERGIC ACTIVITY ACROSS DIFFERENT STRIATAL PROJECTIONS DURING ADAPTIVE AND MALADAPTIVE GROOMING IN FREELY MOVING MICE

Dorsal striatum subregions display a functional heterogeneity in controlling actions on the medio-lateral axis. The medial pole (dorsomedial striatum -DMS) is implicated in actions driven by outcome association such as goal-directed action, while control shifts with laterality to become more automated, habitual and stimulus driven in the lateral pole (dorsolateral striatum - DLS). Nigrostriatal dopaminergic (DA) projections coordinate activity across regions to enable flexible action selection. To investigate the role of dopaminergic DLS-DMS coordination in the context of adaptive and maladaptive repetitive and stereotypic behaviors, we recorded single units in the substantia-nigra pars compacta (SNc), while photo-tagging pathway specific DLS- and DMS-projecting SNc DA neurons in freely moving control and histidine decarboxylase knockout (HDC-KO) mice, an established model of Tourette's syndrome that displays exaggerated grooming responses in grooming induction paradigms.
We characterized these projection- and cell-type-specific populations over repeated open field sessions, capturing both spontaneous and water-drop-induced grooming. Using unsupervised behavioral classification approaches, we framed the different components of grooming behavior and compared the neural signatures of the different nigrostriatal dopaminergic neurons underlying adaptive and maladaptive repetitive behaviors.