Diversity and functions of CNS glia: a transgenic and electrophysiological approach. (360G-Wellcome-080513_Z_06_Z)

Despite the importance of glial cells, our lack of knowledge about their diversity is a major impediment to analyzing their roles in brain function. Here we will address this by: (i) using transgenic techniques to label specific classes of CNS oligodendrocytes and astrocytes in living mice; (ii) studying the labeled oligodendrocytes and astrocytes in live brain slices by electrophysiology and imaging techniques; (iii) using transgenic techniques to disrupt the functions of particular subpop ulations of oligodendrocytes or astrocytes in vivo, and determining the effects on CNS development and function. With this strategy we will investigate the following major questions remaining to be answered about the properties of CNS oligodendrocytes and astrocytes: (a) Do the dorsally- and ventrally-derived subclasses of oligodendrocytes have different electrophysiological properties? (b) Do oligodendrocyte NMDA receptors play a role in controlling myelination? (c) What are the propertie s and function of the NG2-positive putative oligodendrocyte precursor cells? (d) Where are different astrocyte classes generated, and what is their lineage relationship? (e) Do different astrocyte classes have different electrophysiological properties? (f) Do different astrocyte classes have different functions?