The functional equivalence of ascending and parallel fiber inputs in cerebellar computation

At the center of the computational cerebellar circuitry are Purkinje cells, which integrate synaptic inputs from >150,000 granule cell inputs. Traditional theories of cerebellar function assume that all granule cell inputs are comparable. However, it has recently been suggested that the two anatomically distinct granule cell inputs, ascending and parallel fiber, have different functional roles. By systematically examining the efficacy of patches of granule cells with photostimulation, we found no differences in the efficacy of the two inputs in driving the activity of, or in producing postsynaptic currents in, Purkinje cells in cerebellar slices in vitro. We also found that the activity of Purkinje cells was significantly increased upon stimulation of lateral granule cells in vivo. Moreover, when we estimated parallel fiber and ascending apparent unitary EPSC amplitudes using photostimulation in cerebellar slices in vitro, we found them to be indistinguishable. These results are inconsistent with differential functional roles for these two inputs. Instead, our data support theories of cerebellar computation that consider granule cell inputs to be functionally comparable.