DIFFERENT PROPORTIONS OF N-METHYL-D-ASPARTATE AND NON-N-METHYL-D-ASPARTATE RECEPTOR CURRENTS AT THE MOSSY FIBER GRANULE CELL SYNAPSE OF DEVELOPING RAT CEREBELLUM

The mossy fibre granule cell synapse undergoes major developmental changes during the second and third weeks after birth. We investigated synaptic transmission during postnatal days 10-22 by means of whole-cell patch-clamp recordings from granule cells in situ. Parasagittal slices were cut from rat cerebellar vermis, and excitatory postsynaptic currents were evoked in granule cells by mossy fibre stimulation with 1.2 mM Mg++ in the extracellular solution. In the majority of granule cells recorded at postnatal days 16-22, excitatory currents were characterized by a fast initial peak followed by a slower component, while in many of the cells recorded at more immature stages, the fast peak was virtually absent. Pharmacological and kinetic data indicated that the fast and slow components were mediated by non-N-methyl-D-aspartate and N-methyl-D-aspartate receptor activation, respectively. The magnitude of the non-N-methyl-D-aspartate current increased with developmental age, while the magnitude of the NMDA current did not change markedly. The age-dependent change of the non-N-methyl-D-aspartate currents could not be accounted for by changes in recording conditions or granule cell electrotonic properties. Furthermore, from postnatal day 11 to 16 the extent of Mg++ block on the N-methyl-D-aspartate receptor did not change, and could not explain the increasing non-N-methyl-D-aspartate/N-methyl-D-aspartate current ratio. We concluded therefore that the age-dependent increase of the non-N-methyl-D-aspartate cur-rent was the main cause of the different postsynaptic current waveforms observed at different ages. The developmental change in the proportion of N-methyl-D-aspartate and non-N-methyl-D-aspartate currents may be relevant to the processes regulating granule cell maturation and excitability.