Roles of GABAergic inhibition and NMDA receptor subunits in the spatio-temporal integration in the cerebellar cortex of mice

The cerebellar cortex consists of relatively small numbers of identified neuronal types, which form simple and well-defined layers. However, a direct high-resolution demonstration of spatio-temporal pattern of information transmission there has been lacking. Using an optical recording technique with a membrane-potential sensitive dye, we studied the spatio-temporal pattern of excitation propagation induced by white matter stimulation in the slice preparations. We focused on physiological roles of inhibitory synapses and N-methyl-D-aspartate (NMDA) receptors. White matter stimulation induced postsynaptic long-lasting depolarization in the granular layer and transient depolarization in the molecular layer, respectively. Inhibitory synapses modestly suppressed the amplitude of slow depolarization in the granular layer, whereas they exerted powerful lateral inhibition in the molecular layer. Using mutant mice deficient in NMDA receptor subunits NR2A and/or NR2C, we also demonstrated that the NR2A and NR2C subunits expressed in granule neurons contribute to the early and late components of slow depolarization respectively, and that both subunits cooperatively support the temporal summation of depolarization. Taking into account the anatomical organization of the cerebellar cortex, these results might suggest that the granular layer is specialized more in the temporal integration of input signals and the molecular layer in the spatial integration.