This project proposes to develop further a transgenic mouse model of neocortical plasticity in order to investigate the roles of neurotrophins and their receptors, protein kinase A and downstream pathways and serotonin systems in the form of activity-dependent neural plasticity that refines thalamocortical and connections during normal development. In preliminary work, we have already established that many aspects of the physiological plasticity of the developing mouse visual cortex are similar to those in the cat, monkey, ferret, and human that we and others have studied earlier. In all these species, similar competitive interactions between inputs from the two eyes regulate, in an activity-dependent fashion, the relative strength of those inputs (referred to as ocular dominance), and this plasticity is observed only during a well-defined critical period in early life. In the mouse, as in the other species, we have delineated the critical period and have now shown that a brief period of monocular visual occlusion during the critical period results in the loss of responsiveness to the deprived eye and a complementary increase in cortical responses to the open eye; while a similar period of bilateral occlusion has no effect. The present proposal is to build upon this preliminary work to determine whether deletions of genes needed for models of adult plasticity in vitro also alter this form of developmental plasticity thought to be responsible for organizing neuronal connections to and within the developing visual cortex.