Myelin is critical to neuronal function - although previously believed to support only structure, recent research also suggests its importance for neural plasticity (1,2). Among these interested researchers is Dr. Wendy Xin, a postdoctoral fellow in Dr. Jonah Chan’s lab at the Weill Institute for Neurosciences. One of Dr. Xin’s primary research studies includes the investigation of ocular dominance plasticity in which the natural progression of myelination is genetically inhibited in mice. In this study, transgenic Cre Estrogen Receptor (CreER) mice are injected with tamoxifen; Once injected, tamoxifen binds to ER and this activates Cre which causes deletion of the Myrf gene in oligodendrocyte precursor cells (3,4). Myrf is a necessary protein for mature myelinating oligodendrocytes in the central nervous system (CNS). The deletion of Myrf thereafter prevents the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes.

Dr. Xin’s experiment proceeds as the conditional knockout mice (cKO) and the control population both undergo monocular deprivation for four days outside of the critical period (3,5). Both populations are then subjected to ocular dominance tests that quantify the responsiveness of both the deprived and non-deprived eye (3). However, what is not yet known is whether myelination is required for critical period closure - in Dr. Xin’s study the progression of myelination is prevented (by the deletion of Myrf) in order to investigate whether non-myelinated axons in the cKO mice respond differently to changes in the environment outside of the critical period for ocular dominance.

Although our genetic manipulation primarily affects oligodendroglial cells, it is important to investigate whether other cell types that may influence neuronal plasticity are also impacted. One such potential cell type is microglia. Microglia are the immune response cells and phagocytes of the CNS (1,2). I most recently analyzed 18 images of microglia in PDGFRaCreER:Myrf mice that were monocularly deprived at P60 and sacrificed at P90. The analysis was completely blind of which mice were part of the conditional knockout group. Prior to the analysis, the primary hypothesis was that more microglia would be present in the cKO mice; the theory for this being that mice with Myrf floxed in OPC's would die, and that microglia acting as phagocytes in these cKO mice would proliferate. Microglia prevent the build up of toxins in the CNS through phagocytosis and the secretion of enzymes to break down cells (8). Contrary to our hypothesis, I found that the conditional knockout mice had fewer microglia than control mice. This begets the question of whether Myrf deletion impacts the density, morphology and function of microglia.