Impact of developmental glutamatergic signaling on oligodendrocyte differentiation - project oligodendrocytes nervous propagation

The National Institute of Neurological Disorders and Stroke awarded The Regents of the University of Colorado (University of Colorado-Denver) $115,265 on November 27, 2025, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853).

The award funds research investigating how developmental glutamatergic signaling modulates oligodendrocyte differentiation in the early brain. The recipient will use designer receptors exclusively activated by designer drugs (DREADDs) to inhibit or activate neuronal activity in cortical pyramidal neurons in mouse pups, examining long-term consequences of early developmental dysregulation of oligodendrocyte differentiation. The work will investigate the impact of sensory-evoked neuronal activity deprivation on oligodendrocyte development and will characterize oligodendroglial glutamate receptors as potential regulators of oligodendrocyte precursor cell maturation through single-cell RNA sequencing and ex vivo analysis of glutamatergic signaling to ionotropic and metabotropic receptors.

Performance occurs in Colorado. The period of performance extends from November 27, 2025, through October 31, 2027. This is a Project Grant, classified as extramural research supporting basic science investigation of fundamental nervous system structure and function under NINDS's mission to reduce the burden of neurological disease.

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