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The Role of Neuroligin Synaptic Adhesion Proteins on Oligodendrocyte Development and Myelination.

Award Number: R15NS108234
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2029

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The Role of Neuroligin Synaptic Adhesion Proteins on Oligodendrocyte Development and Myelination. - Project Summary Oligodendrocyte progenitor cells (OPCs) are one of the largest pools of dividing cells in the postnatal brain. OPCs produce new oligodendrocytes that remyelinate axons after injury and in demyelinating diseases such as Multiple Sclerosis (MS), as well as demyelination that occurs with neurodegeneration. While many OPCs receive synapses from neurons, the function of these synapses is poorly understood. However, given the number of functional channel proteins, and the timing of the formation of these synapses (they are present prior to OPC differentiation into myelinating oligodendrocytes), it is a reasonable hypothesis that neuron to OPC synaptic activity is instructive for myelination. Neuroligins are synaptic adhesion proteins, that, along with Neurexins, have been implicated in synapse formation and function in neurons and astrocytes. However, their role in oligodendrocytes has not been investigated. We hypothesize that N LGN expression in OPCs is necessary for neuron to OPC synapse formation, and that loss of neuroligins in OPCs will lead to defects in OPC development, function, and myelination. We will determine whether loss of Nlgns in OPCs affects myelination directly, using myelin protein staining, electron microscopy, and immunostaining for the length and number of myelin nodes. We will determine whether neuroligin adhesion proteins are important for tethering neuron to OPC synapses and are instructive for neuron to OPC connections using viral monosynaptic circuit tracing of presynaptic neuronal inputs onto OPCs in OPCspecific Nlgn knockouts. We hypothesize that synaptic connections between neurons and OPCs are important for synaptic development and function, and we will quantify changes in synapse formation using immunohistochemistry for synaptic proteins in vitro as well as electrophysiology and Ca++ imaging in slice. Our preliminary data indicate that loss of Nlgns in OPCs leads to altered proliferation and differentiation, myelin changes, and loss of neuron to OPC connectivity. By the conclusion of these studies, we will know 1. If loss of Nlgns affects OPC development 2. If loss of Nlgns in OPCs disrupts neuron to OPC synapse formation and function 3. If Nlgns are necessary for myelination. Importantly, these projects are independent: it is possible that we find defects in OPC development, but not connectivity, or alterations in myelin wraps but not nodes. These experiments will provide valuable data about OPC development, myelination, and neuron to OPC connectivity that expand our growing knowledge about the role of synaptic proteins expressed in glia, which can inform future therapeutic strategies for white matter dysfunction.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $512,562 )
2026	2026	PRESIDENT AND BOARD OF TRUSTEES OF SANTA CLARA COLLEGE	500 EL CAMINO REAL	SANTA CLARA	CA	95050	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/10/2026	COMPETING CONTINUATION	$512,562
														Subtotal = $512,562

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	PRESIDENT AND BOARD OF TRUSTEES OF SANTA CLARA COLLEGE	500 EL CAMINO REAL	SANTA CLARA	CA	95050	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/21/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $410,984 )
2018	2018	PRESIDENT AND BOARD OF TRUSTEES OF SANTA CLARA COLLEGE	500 EL CAMINO REAL	SANTA CLARA	CA	95050	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/10/2018	NEW	$360,650
2018	2018	PRESIDENT AND BOARD OF TRUSTEES OF SANTA CLARA COLLEGE	500 EL CAMINO REAL	SANTA CLARA	CA	95050	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	8/17/2018	NEW	$50,334
														Subtotal = $410,984

Grand Total All Awards = $923,546

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The Role of Neuroligin Synaptic Adhesion Proteins on Oligodendrocyte Development and Myelination.

Award Number: R15NS108234

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2029

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