ACTIVITY-DEPENDENT REGULATION OF NMDAR1 IMMUNOREACTIVITY IN THE DEVELOPING VISUAL-CORTEX

NMDA receptors have been implicated in activity-dependent synaptic pla sticity in the developing visual cortex. We examined the distribution of immunocytochemically detectable NMDAR1 in visual cortex of cats and ferrets from late embryonic ages to adulthood. Cortical neurons are i nitially highly immunostained. This level declines gradually over deve lopment, with the notable exception of cortical layers 2/3, where leve ls of NMDAR1 immunostaining remain high into adulthood. Within layer 4 , the decline in NMDAR1 immunostaining to adult levels coincides with the completion of ocular dominance column formation and the end of the critical period for layer 4. To determine whether NMDAR1 immunoreacti vity is regulated by retinal activity animals were dark-reared or reti nal activity was completely blocked in one eye with tetrodotoxin (TTX) . Dark-rearing does not cause detectable changes in NMDAR1 immunoreact ivity. However, 2 weeks of monocular TTX administration decreases NMDA R1 immunoreactivity in layer 4 of the columns of the blocked eye. Thus , high levels of NMDAR1 immunostaining within the visual cortex are te mporally correlated with ocular dominance column formation and develop mental plasticity; the persistence of staining in layers 2/3 also corr elates with the physiological plasticity present in these layers in th e adult. In addition, visual experience is not required for the develo pmental changes in the laminar pattern of NMDAR1 levels, but the prese nce of high levels of NMDAR1 in layer 4 during the critical period doe s require retinal activity. These observations are consistent with a c entral role for NMDA receptors in promoting and ultimately limiting sy naptic rearrangements in the developing neocortex.