Cerebellum violates Marr-Albus predictions to train synapses on long-term anticipatory goals

The cerebellar role in motor adaptation rests – according to the foundational theories of Marr and Albus – on the detection of (near)coincident activity between parallel fiber (PF) and climbing fiber (CF) inputs onto Purkinje cells. Supported by numerous in vitro studies, these theories predict synaptic adaptation based on temporal precision detected in time windows of 0ms to ∼100ms. These predictions have not been tested in intact animals. Using two-photon imaging from cerebellar Crus I in intact, awake mice, we show here that coincident stimulation of the PF and CF inputs does not initiate plasticity. Rather, long-term depression (LTD) is reliably evoked by ramping activity of the PF pathway that precedes a CF burst by 400ms. These observations demonstrate a cerebellar plasticity that is not about precision in coincidence with CF signaling. Rather, it shows that cerebellar learning centers on the evaluation of anticipatory PF signals by the CF input.