DECODING THE CEREBELLO-STRIATAL PATHWAY: CELLULAR AND SYNAPTIC MECHANISMS FOR SENSORIMOTOR FUNCTION

The basal ganglia (BG) and the cerebellum have been shown to be involved in both motor- and non-motor functions. Except for the traditional cerebllo-thalamo-cortical pathway, the deep cerebellar nuclei (DCN) also connect with dorsal striatum (DS) via thalamus (TH). The DCN-TH-DS pathway is vital in contributing to execution of motor commands and goal directed behaviors. Although this pathway was shown in slice studies to innervate medium spiny neurons (MSNs) and interneurons, the specific neuronal subtypes receiving cerebellar inputs and their impact on the striatal microcircuitry remain unknown. In addition, sensory and motor processes are tightly linked at the cortical level, however, it is unknown how the convergent sensory inputs from neocortex and cerebellum integrate at the BG level and affect sensorimotor processes. To investigate the cellular and network mechanisms, we performed in vivo whole-cell patch clamp recordings in head-restrained mice, combining optogenetic manipulation of the cerebello-striatal pathway with sensory stimulation. We found for the first time that optogenetic activation of the DCN elicited subthreshold excitatory postsynaptic potentials (EPSPs) or action potentials in both direct- and indirect-pathway MSNs, as well as in cholinergic interneurons. The latency between light pulse onset and EPSPs initiation ranged from tens to hundreds of milliseconds, suggesting involvement of both disynaptic and polysynaptic pathways. These findings demonstrate that cerebellar output robustly influences DS in vivo, and may modulate sensory processing by striatal circuits. Future studies will focus on elucidating the functional integration of cerebellar output and sensory inputs at the striatal level.