The sites and mechanisms of long-term synaptic plasticity (LTP and LTD) in the cerebellar cortex are object of debate. What is apparently lacking is a determination of the plastic changes occurring when the whole circuit is engaged. In this way, LTP and LTD may occur at multiple sites as well as in the intrinsic excitable mechanisms of these same neurons. In particular, we have tested the impact of theta burst stimulation (TBS) delivered to the mossy fibers (Mapelli and D'Angelo, 2007).

Voltage-Sensitive Dye (VSD) imaging on rat cerebellar slices showed various areas of plasticity following TBS, with a remarkable prevalence of LTD in the granular layer and of LTP in the Purkinje cell layer. At the same time, firing changes were monitored in Purkinje cells (PCs) and molecular layer interneurons (MLIs) using paired loose cell-attached (n=5) and whole-cell recordings (n=5). The PCs showed enhanced probability of response and enhanced time precision with reduced first spike delay. This could be due either to a secondary reduction of MLIs activity (which showed depression of response in the majority of cases) or to enhanced parallel fiber – Purkinje cells transmission, or both. While these mechanistic hypotheses are currently under investigation, these results already indicate that afferent patterns cause distributed plasticity in the network suggesting that chains of changes are the salient aspect to be considered in order to interpret the processes of cerebellar learning.