Convergence of inputs from the basal ganglia with layer 5 of motor cortex and cerebellum in mouse motor thalamus

Abstract A key to motor control is the motor thalamus, where several inputs converge. One excitatory input originates from layer 5 of primary motor cortex (M1 L5 ), while another arises from the deep cerebellar nuclei (Cb). M1 L5 terminals distribute throughout the motor thalamus and overlap with GABAergic inputs from the basal ganglia output nuclei, the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr). In contrast, it is thought that Cb and basal ganglia inputs are segregated. Therefore, we hypothesized that one potential function of the GABAergic inputs from basal ganglia is to selectively inhibit, or gate, excitatory signals from M1 L5 in the motor thalamus. Here, we tested this possibility and determined the circuit organization of mouse (both sexes) motor thalamus using an optogenetic strategy in acute slices. First, we demonstrated the presence of a feedforward transthalamic pathway from M1 L5 through motor thalamus. Importantly, we discovered that GABAergic inputs from the GPi and SNr converge onto single motor thalamic cells with excitatory synapses from M1 L5 and, unexpectedly, Cb as well. We interpret these results to indicate that a role of the basal ganglia is to gate the thalamic transmission of M1 L5 and Cb information to cortex. Significance Statement In this study, we extend the common conception of the basal ganglia as an information loop: flowing from cortex to basal ganglia, to thalamus, and back to cortex. We used tricolor viral labeling and an optogenetic approach to reveal that projections from the output nuclei of the basal ganglia converge with inputs from both layer 5 of primary motor cortex and the deep cerebellar nuclei onto individual thalamic relay cells. Not only do these findings add nuance to the notion that cerebellar and basal ganglia circuits through motor thalamus are independent, but also highlight a novel intersection between basal ganglia and cortex that countervails long-held conceptions of how the brain handles motor commands.