Ventromedial Thalamus-Projecting DCN Neurons Modulate Associative Sensorimotor Responses in Mice

The deep cerebellar nuclei (DCN) integrate various inputs to the cerebellum and form the final cerebellar outputs critical for associative sensorimotor learning. However, the functional relevance of distinct neuronal subpopulations within the DCN remains poorly understood. Here, we examined a subpopulation of mouse DCN neurons whose axons specifically project to the ventromedial (Vm) thalamus (DCN Vm neurons), and found that these neurons represent a specific subset of DCN units whose activity varies with trace eyeblink conditioning (tEBC), a classical associative sensorimotor learning task. Upon conditioning, the activity of DCN Vm neurons signaled the performance of conditioned eyeblink responses (CRs). Optogenetic activation and inhibition of the DCN Vm neurons in well-trained mice amplified and diminished the CRs, respectively. Chemogenetic manipulation of the DCN Vm neurons had no effects on non-associative motor coordination. Furthermore, optogenetic activation of the DCN Vm neurons caused rapid elevated firing activity in the cingulate cortex, a brain area critical for bridging the time gap between sensory stimuli and motor execution during tEBC. Together, our data highlights DCN Vm neurons’ function and delineates their kinematic parameters that modulate the strength of associative sensorimotor responses.