A previous mRNA microarray analysis identified components of JAK/STAT immune signaling, in particular STAT1, as being significantly upregulated in visual cortex during the critical period following long-term sensory deprivation. STAT1 is activated by cytokines such as IFN-gamma and induces transcription of immune-related genes. However, little is known about the role of STAT1 in cortical plasticity. We found that STAT1, increased after monocular deprivation (MD), acts to inhibit plasticity, suggesting that STAT1 signaling is a part of a negative feedback loop to regulate plasticity. Ocular dominance plasticity was measured using optical imaging, where we examined the intrinsic signal strength of the deprived vs. non-deprived (open) eye in the binocular region of primary visual cortex. IFN-gamma, which increases the level of STAT1, blocked plasticity induced by MD. On the other hand, STAT1 knockout (STAT1-/-) mice showed enhanced plasticity in adult mice, due to accelerated increase of the response from the open eye. Also during the critical period, STAT1-/- mice showed early increase of the open eye response after short-term (4 day) MD. In control wild-type (WT) mice, plasticity after short-term MD was mediated by a decreased response from the deprived eye and the response from the open eye was increased only after long-term (7-8 day) MD. These results strongly suggest that STAT1 regulates homeostatic upregulation of the open eye response, so that removing STAT1 inhibition accelerates the homeostatic response. In ongoing experiments, we have identified specific molecular signals downstream of STAT1 that implement such plasticity.

Society for Neuroscience Abstract, 2011.