Ischemic stroke results in acute deficits which can be profoundly disabling. Although spontaneous recovery occurs in the following months, it is often incomplete and leaves patients in a state of chronic disability. We are interested in the mechanisms that drive this recovery in order to find novel targets to improve the recovery ceiling. Remapping of infarcted representations into perilesional tissue is thought to be a critical aspect of recovery, but it is not clear what mechanisms are responsible or how it may be a useful target for rehabilitation. Using a mouse model of focal ischemia, we examining genes required for remapping and behavioral recovery. So far we have found that mice deficient for Activity-regulated cytoskeleton-associated protein (Arc) have attenuated remapping and persistent behavioral deficits. Furthermore, we have found that focal sensory deprivation, targeted to the peri-lesional cortex, redirects remapping to that location acceleration both remapping and behavioral recovery.The brain at rest exhibits robust spontaneous activity that is highly organized. Commonly measured with functional connectivity (FC), these relationships can be modified with learning or modified sensory experience. We are interested in the molecular mechanisms that drive whole-brain network changes. Using functional optical intrinsic signal imaging to measure ISA in mice, we have found that visual deprivation during the critical period causes dramatic reorganization in whole-cortex ISA pattern as measured by FC. Furthermore, we found that these changes are attenuated in Activity-regulated cytoskeleton-associated protein (Arc) knock-out mice. Taken together, these findings show that experience-dependent changes in whole-cortex ISA patterns are driven by Arc-mediated synaptic plasticity.