Models of calcium dynamics in cerebellar granule cells

Intracellular calcium dynamics is critical for many functions of cerebellar granule cells (GrCs) including membrane excitability, synaptic plasticity, apoptosis, and regulation of gene transcription. Recent measurements of calcium responses in GrCs to depolarization and synaptic stimulation reveal spatial compartmentalization and heterogeneity within dendrites of these cells. However, the main determinants of local calcium dynamics in GrCs are still poorly understood. One reason is that there have been few published studies of calcium dynamics in intact GrCs in their native environment. In the absence of complete information, biophysically realistic models are useful for testing whether specific Ca(2+) handling mechanisms may account for existing experimental observations. Simulation results can be used to identify critical measurements that would discriminate between different models. In this review, we briefly describe experimental studies and phenomenological models of Ca(2+) signaling in GrC, and then discuss a particular biophysical model, with a special emphasis on an approach for obtaining information regarding the distribution of Ca(2+) handling systems under conditions of incomplete experimental data. Use of this approach suggests that Ca(2+) channels and fixed endogenous Ca(2+) buffers are highly heterogeneously distributed in GrCs. Research avenues for investigating calcium dynamics in GrCs by a combination of experimental and modeling studies are proposed.