Differential NMDA and GABA-A receptor expression during critical period neuroplasticity of the cat visual cortex.

摘要

Neuronal plasticity in normal cat development is low after birth, peaks at 5 weeks and declines to a low level by 20 weeks. Dark rearing (DR) slows the progression of the critical period in visual cortex such that at 5 weeks of age, normal cats are more plastic than DR cats, but at 20 weeks, DR cats are more plastic than normal cats.; Changes in the subunit compositions of NMDA and GABA-A receptors and a shifting balance between excitation and inhibition may be part of the molecular basis for critical period plasticity. Basically, two lines of experiments were used to test this possibility. The first line was to investigate the normal postnatal development profile for major NMDA subunits and GABA-A alpha subunits; and the second line was to detect the influence of visual input on their expression patterns. These two lines were integrated by western/northern studies to determine subunits in level expression and by immunohistochemistry studies to determine subunits in cellular/laminar expression. The expression patterns of NR2A, NR2B, and NR1 for NMDA receptors and α₁, α ₂, and α₃ for GABA-A receptors were studied.; Our results show that subunit compositions of NMDA and GABA-A receptors are developmentally regulated and the changes of the mature subunits correlate to the time course of the critical period. A sharp increase in mature NMDA and GABA-A subunits occurs in concert during the rising phase of critical period plasticity. After the peak of the critical period, expression of mature GABA-A receptors surpasses that of NMDA receptors. For both NMDA and GABA-A receptors, dark rearing affects the development of mature subunits. It slows the maturation of NR2A receptors and accelerates the maturation of GABA-A α ₁ receptors. The developmental changes also vary with layers of the visual cortex with the major changes occurring in layer IV. The changes of NR2A and NR2B tend to be parallel to each other but opposite to the changes of NR1.; The present results strongly support that the subunit compositional changes of and the balance between NMDA and GABA-A receptors are involved in the critical period plasticity of the cat visual cortex.