Cerebellar long-term depression might normalize excitation of Purkinje cells: a hypothesis.

Long-term depression (LTD) of parallel-fibre (PF) synapses on Purkinje cells is usually interpreted in the context of a specific theory of motor learning by the cerebellum proposed by Marr, Albus and Ito. Several arguments suggest that this theory might be false. A new hypothesis about the role of cerebellar LTD proposes that, under physiological conditions, LTD is autoinduced by PF inputs. This proposal is based on the capacity of PF inputs to trigger influx of Ca2+ into the dendrite. Long-term depression and other forms of Purkinje-cell synaptic plasticity are part of a local negative feedback loop that prevents overstimulation of Purkinje cells by PF inputs. This theory explains why it is difficult to induce LTD when a normal level of inhibition is present, and why inhibitory inputs are potentiated by the same conditions that can induce LTD of PF synapses.