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Spatio-Temporal Recoding or Information at the input Stage of the Cerebellum by Long-Term Synaptic Plasticity

Egidio D’Angelo

Dept. Physiological and Pharmacological Sciences, University of Pavia , Italy

Long-term potentiation (LTP) is a persistent enhancement of synaptic transmission thought to provide the cellular basis for information storage in brain neuronal circuits. Since neuronal circuits usually process spike sequences, a central issue is to understand how LTP affects neurotransmission dynamics. In principle, the effect of pre- and postsynaptic changes should be different, since neurotransmitter release and postsynaptic receptor activation have different time-dependent properties. To this end, we have investigated LTP regulation of short-term plasticity and spike discharge at the mossy fiber – granule cell synapse of cerebellum, at which LTP is expressed through an increased release probability (Sola et al., J.Physiology, 2004). By using whole-cell patch-clamp recordings in P19-P22 rat cerebellar slices, we found that LTP accelerated EPSC train depression and enhanced sustained (probably spillover-mediated) AMPA and NMDA receptor currents. Moreover, output spike bursts were anticipated and intensified. To interpret the role of presynaptic dynamics, glutamate spillover, and postsynaptic receptor activation we developed a mathematical model of the mossy fiber – granule cell relay in NEURON. The model showed that raising release probability could explain the changes in synaptic currents and spike bursts. Simulations showed that the effects of release probability required glutamate spillover in the cerebellar glomerulus and could not be replicated by a receptor conductance increase. Regulation of spike burst initiation and frequency by long-term synaptic plasticity provides a mechanisms for adaptable information coding at the input stage of cerebellum.

A second main issue is how information is spatially organized and how its flow is regulated by synaptic plasticity. We have investigated this issue by performing multi-electrode array (MEA) recordings in cerebellar slices. We have found that inhibitory GABAergic activity limits the spread of excitation and regulates the induction of bidirectional long-term synaptic plasticity according to a Bienenstok-Cooper-Munro (BCM) rule based on the intensity of postsynaptic activation. This mechanism, which sharpens the contrast between neighboring excited and inhibited areas, could play an important role to determine the subsequent spatial activation pattern of Purkinje cells and molecular layer interneurons.

These investigations suggest an important role of long-term synaptic plasticity for spatio/temrporal reconfiguration of information at the input stage of the cerebellum.

Supported by FIRB projects of MIUR and EU projects CEREBELLUM and SPIKEFORCE.