| Experience shapes neural circuits during critical periods in early life. Clear evidence for a critical period has been found in the visual system. During a critical period, manipulations of visual experience can induce changes in ocular dominance in the visual cortex. However, the role of critical period plasticity in normal development is unknown. Here I show that before the critical period, the preferred orientations of individual cortical cells are mismatched through the two eyes and the mismatch decreases and reaches adult levels by the end of the period. The binocular matching of orientation preference requires normal visual experience and NMDA receptor activation during a critical period. Binocular matching can be delayed by visual deprivation from birth and blocked in mutant mice that have reduced level of cortical inhibition, like that of ocular dominance plasticity. These results demonstrate that activity-dependent changes induced by normal visual experience during the critical period serve to match eye-specific inputs in the cortex, thus revealing a physiological role for critical period plasticity during normal development.;Because the timing of critical periods is regulated by both genetics and the environment, I further studied the functional significance of temporal regulation for binocular matching of orientation preference. I found that the binocular matching is permanently disrupted in mice with a precocious critical period due to genetically enhanced synaptic inhibition. The disruption is specific to one type of neurons, the complex cells, which, as I reveal, normally match after the simple cells. Furthermore, environmental enrichment completely rescues the matching deficit by shifting the matching process to coincide with the precocious plasticity. Similarly, in a mouse model of Rett syndrome, I reveal that the critical period of ocular dominance plasticity is advanced and the binocular matching fail to occur.;Taken together, my thesis work uncovers a functional purpose for the critical period during normal development. In addition, my work further demonstrates that the proper timing of the critical period is essential for establishing normal binocularity and that the detrimental impact of its genetic misregulation can be ameliorated by environmental manipulations. |
