Variations in the tangential distribution of postsynaptic glutamate receptors in Purkinje cell parallel and climbing fiber synapses during development

Abstract

Major factors affecting the responses of a neuron to release of glutamate include the kinds and distribution of glutamate receptors in the neuron and their distribution along the surface of the postsynaptic membrane (tangential distribution). The latter distribution pattern is established during the development of the synapse and could be modified during maturation of synapse structure/function and through adult synapse plasticity. Parallel and climbing fiber synapses of cerebellar Purkinje cells are good models for studying this pattern because they contain two major kinds of ionotropic glutamate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and delta, that are involved in adult plasticity and show differences in distribution, and because these two synapse types show complex changes in architecture and glutamate receptor distributions during development. In the present study, both AMPA and delta receptors showed variations in tangential distributions during many stages of development from postnatal day 2 to adult; i.e. qualitative assessment showed that receptors are concentrated either near the center or in outer portions of the synapse, while they are rare or absent from the perisynaptic region. Quantitative analysis showed statistically significant nonuniformities at some ages; the most common nonuniformity in these cases appears to be a drop-off in receptor density in the outer 20% of the synapse. Statistical analyses also indicated that distribution patterns did not change significantly with age. In contrast to the ionotropic receptors, the metabotropic glutamate receptor, mGluR1 α, was found mainly in the perisynaptic region both during development and in adults. Differences in the distribution of glutamate receptors may be necessary to assure an effective 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 established early in development, indicating that the postsynaptic density/membrane region is highly organized even in the immature synapse.