Impact of Developmental Glutamatergic Signaling on Oligodendrocyte Differentiation

University Of Colorado Denver, Aurora CO

Investigators

Abstract

Project Oligodendrocytes nervous propagation. involves proliferation development. developing chemogenetically preliminary precursor development of also maturation. early Here elucidate glutamate Summary (OLs) produce myelin, a lipid rich membrane that wraps neuronal axons in the central system to provide them with metabolic and trophic support and allow for faster action potential Developmental myelination requires precise spatial and temporal regulation that likely communication between OLs and neurons. In the mature brain, neuronal activity promotes OL and differentiation, but less i s known about how oligodendrocytes mature in early brain To test how glutamatergic neuronal activity modulates OL differentiation in the early brain, we use designer receptors exclusively activated by designer drugs (DREADDs) to inhibit or activate activity in cortica pyramidal neurons in mouse pups. Our data show that r educing neuronal activity n early development unexpectedly causes OL cells (OPCs) to differentiate prematurely, whereas increasing neuronal activity in early inhibits OPC differentiation. Here we propose to investigate the long-term consequences early developmental dysregulation of oligodendrocyte differentiation on later development. We will investigate the impact of deprivation of sensory-evoked neuronal activity on oligodendrocyte Additionally, we identified oligodendroglial glutamate receptors as potential regulators of OPC maturation in response to neuronal glutamatergic activity by single cell RNA sequencing. we urther investigate he role of glutamatergic activity on oligodendrocyte differentiation and the mechanisms of glutamatergic signaling to oligodendroglial ionotropic and metabotropic receptors ex vivo. l i f t