Associative plasticity of granule cell inputs to cerebellar Purkinje cells

Abstract

AbstractGranule cells of the cerebellum make up to 175 000 excitatory synapses on a single Purkinje cell, encoding the wide variety of information from the mossy fibre inputs into the cerebellar cortex. The granule cell axon is made of an ascending portion and a long parallel fibre extending at right angles, an architecture suggesting that synapses formed by the two segments of the axon could encode different information. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that AA and PF synapses encode different information, and that association of these distinct inputs to Purkinje cells might be relevant to the circuit and trigger plasticity, similarly to the coincident activation of PF and climbing fibre inputs. Here we describe a new form of associative plasticity between these granule cell inputs, and show for the first time that synchronous AA and PF repetitive train stimulation, with inhibition intact, triggers long term potentiation (LTP) at AA synapses specifically. Furthermore, the timing of presentation of the two inputs controls the outcome of plasticity and induction requires NMDAR and mGluR activation. These observations reinforce the suggestion that AA and PF synapses are two synaptic populations with different coding capabilities and plasticity. Associative plasticity of AA and PF synapses enables effective association of information transmitted via granule cells.