Morphological Alterations in the Cerebellar Granule Cell Layer of Mice Lacking Calretinin

Abstract

Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in the central nervous system, but their physiological functions remain poorly understood. Calretinin is expressed in cerebellar granule cells and calretinin deficient mice suffer from alterations in motor coordination. Using confocal microscopy, we demonstrate that calretinin deficient mice exhibit a significantly decreased density of granule cells at the level of the cerebellar cortex. Moreover, it has been shown that migration of granule cells is tighly associated with intracellular calcium fluctuations. Therefore, we hypothesize that the perturbation of the calcium dynamics in calretinin deficient mice may be the cause of the observed morphological alterations. To test this assumption, we are currently developping two strategies.First, using confocal microscopy and cerebellar microexplant cultures, we are studying calcium transients occuring during granule cell migration in wild type and calretinin knock-out mice. On the other hand, we are developping a dedicated computational model for [Ca2+]i transients that takes into account calcium fluxes through the plasma and ER membrane. This model will shed light on the possible mechanism responsible for the modulation by calretinin of calcium dynamics during granule cell migration.