QUANTITATIVE AND QUALITATIVE CHANGES IN AMPA RECEPTOR EXPRESSION DURING SPINAL-CORD DEVELOPMENT

Synaptic activity in early postnatal life is important for the acquisi tion of mature structural and functional properties of neurons. Previo us studies indicate that the mature molecular features of spinal motor neurons emerge during a period of activity-dependent development in e arly postnatal life. Since glutamatergic synaptic transmission provide s the major excitatory drive into motor neurons, glutamate receptors a re likely to play a central role in motor neuron activity-dependent de velopment. To gain insight into this process, we have used receptor au toradiography, immunoblotting and immunohistochemistry to determine th e distribution, temporal expression and potential sub unit composition of lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype gl utamate receptors in the developing rat spinal cord. Using two differe nt ligands, lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid an d [H-3]-6-cyano-7-nitroquinoxaline-2,3-dione, we find that lpha-amino- 3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites in the adul t are largely restricted to the substantia gelatinosa. In marked contr ast, during early postnatal life, lpha-amino-3-hydroxy-5-methyl-4-isox azolepropionic acid binding sites are transiently expressed at high le vels in the ventral horn. This parallels previous findings on the deve lopmental regulation of N-methyl-D-aspartate receptor expression. Usin g lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor sub unit-specific antibodies we show by immunoblot analysis and immunohist ology that, to varying degrees, the expression patterns of glutamate r eceptor subunit 1 and glutamate receptor subunits 2/3 are significantl y developmentally regulated. The most conspicuous change is the downre gulation of glutamate receptor 1 expression within motor neurons over the first three weeks of postnatal life. The qualitative and quantitat ive changes we observe in glutamate receptor expression in early postn atal life are likely to have a major impact on the electrophysiologica l properties of young motor neurons and thus may contribute to their a ctivity-dependent development.