Nogo Receptor in PlasticityMonocular deprivation normally alters ocular dominance in the visual cortex
only during a postnatal critical period (20 to 32 days postnatal in mice). This is a period when intracortical myelination is reaching adult levels. Therefore, we focused on the role of the myelin inhibitor pathway in plasticity. Mutations in the Nogo-66 receptor (NgR1) affect cessation of ocular dominance plasticity. In NgR1-/- mice, plasticity during the critical period is normal, but it continues abnormally such that ocular dominance at 45 or 120 days postnatal is subject to the same plasticity as at juvenile ages. Thus, physiological NgR signaling from myelin-derived Nogo, MAG, and OMgp consolidates the neural circuitry established during experience-dependent plasticity.
Our current work explores the anatomical basis of NgR1-regulated plasticity. We hypothesize that alterations in Anatomical Plasticity underlie the electrophysiological evidence of increased cortical plasticity. We are using in vivo imaging and conditional NgR1 alleles to test the ability of this pathway to titrate adult Anatomical Plasticity in the mouse cerebral cortex. Such regulation may underlie the genetic linkage of NgR1 mutations we have described in human Schizophrenia (dysfunction of one Schizophrenia derived human NgR1 mutation shown below).