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 subpopulations 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 gradient refractive index (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, through a glass window or a GRIN lens, respectively. MSNs showed a sustained population activity throughout movement duration that peaked at movement offset. In contrast, their cortical and thalamic inputs showed opposing activity dynamics, with corticostriatal activity concentrated around movement onset and offset and thalamostriatal activity engaged during movements. To examine activity differences among dMSNs and iMSNs and their inputs, we developed Trial Ensemble Attention network (TEA-net) – a recurrent neural network (RNN) with attention that leverages trial-to-trial variability –to predict the neuronal type based on their activity. This approach followed by clustering analysis identified quintessential activity patterns that were distinct between dMSNs and iMSNs and between cortical and thalamic neurons that specifically project onto them. The results provide insights into the mechanisms of integration of distinct long-range inputs carrying diverse information by MSN subpopulations.