Cerebellar climbing fibers impact experience-dependent plasticity in the mouse primary somatosensory cortex

In the cerebellum, climbing fibers (CFs) provide instructive signals for supervised learning at parallel fiber to Purkinje cell synapses. It has not been tested so far whether CF signaling may also influence plasticity in other brain areas. Here, we show that optogenetic CF activation suppresses potentiation of whisker responses in L2/3 pyramidal cells in primary somatosensory cortex (S1) of awake mice that is observed after repeated whisker stimulation. Using two-photon imaging and chemogenetics, we find that CFs control plasticity by modulating SST- and VIP-positive interneurons in S1 cortex. Transsynaptic labeling identifies zona incerta (ZI) to thalamic posterior medial nucleus projections as a pathway for cerebellar output reaching S1 cortex. Chemogenetic inhibition of PV-positive neurons in the ZI prevents CF co-activation effects, identifying the ZI as a critical relay. Our findings demonstrate that CFs impact sensory signal processing and plasticity in S1 cortex and thus may convey instructive signals.