Dissection of inter-area interactions of motor circuits

Motor behaviors arise from dynamic interactions of interconnected neural populations across distributed brain areas. The underlying principles of information flow remain largely unknown. Here, we investigate the functional roles of motor cortex and intralaminar thalamus in driving specific cell populations of the striatum - the input nucleus of the basal ganglia - during movements. We recorded the activity of direct and indirect pathway medium spiny neurons (dMSNs and iMSNs) in the striatum as mice performed a skilled motor task, by in vivo two-photon calcium imaging through GRIN lens. Furthermore, using monosynaptic pseudo-typed rabies virus we identified and imaged the activity of corticostriatal and thalamostriatal neurons that specifically project to dMSNs and iMSNs. To explore activity differences among dMSNs and iMSNs and their inputs, we developed Trial Ensemble Attention network (TEA-net) – a recurrent neural network with attention that classifies neurons based on ensembles of their single-trial activity. This approach followed by clustering analysis identified heterogeneous functional subpopulations, some of which are dominated by dMSNs or iMSNs. The activity patterns of the inputs to dMSNs and iMSNs were less distinct from each other. Preliminary experiments imaging striatal activity during optogenetic manipulation of the inputs suggest that cortical and thalamic inputs contribute differentially to striatal activity in a target cell-type specific manner. The findings provide insights on the contributions of diverse long-range inputs to MSN subpopulation activity.