Cerebellum Gates Plasticity of Somatosensory Cortex

In classic theories of motor learning, the cerebellar cortex is the primary storage site of the engram. In addition to its role in motor control, cerebellar activity influences sensory perception and cognition. For these forms of learning, the engram may be stored in cerebellar target regions including the neocortex, where plasticity is known to underlie changes in sensory perception and complex behavior. While modulation of cerebellar output has indeed been shown to influence the activity and plasticity of most neocortical areas, the cellular details of this interaction are not known. A compelling possibility is that cerebellar climbing fiber (CF) signals – required for normal activity and plasticity of the cerebellar cortex – also control activity and plasticity of the neocortex. In this thesis, I test whether CF activation in the cerebellar cortex is sufficient to influence sensory-evoked responses and experience-dependent plasticity of primary somatosensory cortical (S1) neurons. I demonstrate that sensory experience – here, a bout of rhythmic whisker stimulation – increases the activity of excitatory neurons and concomitantly decreases the activity of inhibitory neurons in L2/3 of S1 in awake mice, effects which are blocked by CF co-activation during the sensory experience. Importantly, S1 plasticity phenomena are associated with increased behavioral responsivity to subsequent sensory stimuli, which does not occur if CFs are co-activated. Using two-photon calcium imaging and bidirectional chemogenetic manipulation of S1 neurons, I found that CFs control S1 plasticity by differentially modulating S1 SST- and VIP-expressing interneurons. Transsynaptic labeling, electrophysiological, and two-photon calcium imaging approaches identify the zona incerta as a critical node in the transmission of CF signals to S1. Taken together, these findings reveal that CFs gate S1 plasticity, thereby modulating responsivity to sensory stimuli.