Striatal cholinergic interneurons generate beta and gamma oscillations in the corticostriatal circuit and produce motor deficits

Significance Exaggerated beta oscillations within the cortico-basal ganglia-thalamic (CBT) network are putative electrophysiological signatures of bradykinesia and rigidity in Parkinson’s disease (PD). However, it is unclear how exaggerated beta oscillations emerge and how such oscillation patterns are related to PD motor deficits. In this study, we demonstrate that a single cell type, the striatal cholinergic interneuron, mediates the emergence of exaggerated beta oscillations within CBT circuits of normal mice and induces parkinsonian-like motor deficits. Because the striatal cholinergic system is uninhibited by loss of dopamine, these results provide mechanistic insights into the therapeutic effects of anticholinergic drugs in the treatment of PD and highlight the potential for developing beta oscillation-based biomakers for PD. Cortico-basal ganglia-thalamic (CBT) neural circuits are critical modulators of cognitive and motor function. When compromised, these circuits contribute to neurological and psychiatric disorders, such as Parkinson’s disease (PD). In PD, motor deficits correlate with the emergence of exaggerated beta frequency (15–30 Hz) oscillations throughout the CBT network. However, little is known about how specific cell types within individual CBT brain regions support the generation, propagation, and interaction of oscillatory dynamics throughout the CBT circuit or how specific oscillatory dynamics are related to motor function. Here, we investigated the role of striatal cholinergic interneurons (SChIs) in generating beta and gamma oscillations in cortical-striatal circuits and in influencing movement behavior. We found that selective stimulation of SChIs via optogenetics in normal mice robustly and reversibly amplified beta and gamma oscillations that are supported by distinct mechanisms within striatal-cortical circuits. Whereas beta oscillations are supported robustly in the striatum and all layers of primary motor cortex (M1) through a muscarinic-receptor mediated mechanism, gamma oscillations are largely restricted to the striatum and the deeper layers of M1. Finally, SChI activation led to parkinsonian-like motor deficits in otherwise normal mice. These results highlight the important role of striatal cholinergic interneurons in supporting oscillations in the CBT network that are closely related to movement and parkinsonian motor symptoms.