VARIATIONS IN THE TANGENTIAL DISTRIBUTION OF POSTSYNAPTIC GLUTAMATE RECEPTORS IN PURKINJE-CELL PARALLEL AND CLIMBING FIBER SYNAPSES DURING DEVELOPMENT

Major factors affecting the responses of a neuron to release of glutam ate include the kinds and distribution of glutamate receptors in the n euron and their distribution along the surface of the postsynaptic mem brane (tangential distribution). The latter distribution pattern is es tablished during the development of the synapse and could be modified during maturation of synapse structure/function and through adult syna pse plasticity. Parallel and climbing fiber synapses of cerebellar Pur kinje cells are good models for studying this pattern because they con tain two major kinds of ionotropic glutamate receptors, alpha-amino-3- hydroxy-5-methyl-4-isoxazole propionate (AMPA) and delta, that are inv olved in adult plasticity and show differences in distribution, and be cause these two synapse types show complex changes in architecture and glutamate receptor distributions during development. In the present s tudy, both AMPA and delta receptors showed variations in tangential di stributions during many stages of development from postnatal day 2 to adult; i.e. qualitative assessment showed that receptors are concentra ted either near the center or in outer portions of the synapse, while they are rare or absent from the perisynaptic region. Quantitative ana lysis showed statistically significant nonuniformities at some ages; t he most common nonuniformity in these cases appears to be a drop-off i n receptor density in the outer 20% of the synapse. Statistical analys es also indicated that distribution patterns did not change significan tly with age. In contrast to the ionotropic receptors, the metabotropi c glutamate receptor, mGluR1 alpha, was found mainly in the perisynapt ic region both during development and in adults. Differences in the di stribution of glutamate receptors may be necessary to assure an effect ive response to glutamate release and may be modified through synaptic plasticity. Our findings show that the basic patterns of distribution of ionotropic and metabotropic glutamate receptors in synapses are es tablished early in development, indicating that the postsynaptic densi ty/membrane region is highly organized even in the immature synapse. P ublished by Elsevier Science Ltd.