Impact of Developmental Glutamatergic Signaling on Oligodendrocyte Differentiation

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

Grant Number: 1F31NS139593-01A1
NIH Institute/Center: NIH
Principal Investigator: Tessa Allen