A striatal SOM-driven ChAT-iMSN loop generates beta oscillations and produces motor deficits.

Enhanced beta oscillations within the cortico-basal ganglia-thalamic (CBT) network are correlated with motor deficits in Parkinson's disease (PD), whose generation has been associated recently with amplified network dynamics in the striatum. However, how distinct striatal cell subtypes interact to orchestrate beta oscillations remains largely unknown. Here, we show that optogenetic suppression of dopaminergic control over the dorsal striatum (DS) elevates the power of local field potentials (LFPs) selectively at beta band (12–25 Hz), accompanied by impairments in locomotion. The amplified beta power originates from a striatal loop driven by somatostatin-expressing (SOM) interneurons and constituted by choline acetyltransferase (ChAT)-expressing interneurons and dopamine D2 receptor (D2R)-expressing medium spiny neurons (iMSNs). Moreover, closed-loop intervention selectively targeting striatal iMSNs or ChATs diminishes beta oscillations and restores motor function. Thus, we reveal a striatal microcircuit motif that underlies beta oscillation generation and accompanied motor deficits upon perturbation of dopaminergic control over the striatum. [Display omitted] • Inhibition of DANs selectively enhances beta oscillations and produces motor deficits • SOMs function as the downstream effectors for DANs in beta oscillation generation • The amplified beta power originates from a striatal SOM-driven ChAT-iMSN loop • Closed-loop inhibition iMSNs or ChATs reduces beta power and improves motor deficits Qian et al. demonstrate that photoinhibition of substantia nigra pars compacta (SNc) dopaminergic terminals in striatum enhances beta oscillations, accompanied by impairment in locomotion. Specifically, the enhancement in beta power originates from a loop circuit driven by somatostatin interneurons and constituted by cholinergic interneuron and D2R medium spiny neurons. [ABSTRACT FROM AUTHOR]