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Molecular mechanisms of structural plasticity of inhibitory GABAergic interneurons

Award Number: R01MH118442
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/13/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Molecular mechanisms of structural plasticity of inhibitory GABAergic interneurons - Abstract. This proposal aims to investigate the molecular basis of structural plasticity of inhibitory GABAergic interneurons (INs) in the mammalian forebrain. Cortical and hippocampal INs play critical roles in perception and memory storage; their abnormalities have been associated with a broad spectrum of neurological disorders in humans. It is well-established that INs undergo morphological changes and reorganize their networks after sensory experience. This phenomenon appears to be equally important for assembly of synaptic connectivity during development and for processing of information in the brain across lifespan, but the underlying molecular mechanisms are poorly understood. By using unbiased screening and mouse genetics, we have identified transcription factors (TFs) that regulate the architectures of IN networks in the hippocampus. Our preliminary studies support the hypothesis that these TFs are essential for appropriate GABAergic inhibition of pyramidal neurons and memory storage. We will use innovative approaches to elucidate the role of transcription in inhibitory circuits in unique mouse models. Our specific aims are: 1) To test how ablation of TFs in genetically defined IN subtypes impacts their morphologies, wiring and physiology; 2) To examine the consequences of TF signaling on sensory processing and memory formation; and 3) To identify TF effector genes. Taken together, these studies will provide new and significant insights into thus far poorly understood molecular mechanisms of IN plasticity.


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: 2023 ( Subtotal = $640,814 )
2023	2023	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	5	4/12/2023	NON-COMPETING CONTINUATION	$640,814
														Subtotal = $640,814

Issue Date FY: 2022 ( Subtotal = $659,196 )
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	4	6/29/2022	NON-COMPETING CONTINUATION	$659,196
														Subtotal = $659,196

Issue Date FY: 2021 ( Subtotal = $659,196 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	3	3/30/2021	NON-COMPETING CONTINUATION	$659,196
														Subtotal = $659,196

Issue Date FY: 2020 ( Subtotal = $751,941 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	2	4/6/2020	NON-COMPETING CONTINUATION	$751,941
														Subtotal = $751,941

Issue Date FY: 2019 ( Subtotal = $732,591 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	6/13/2019	NEW	$732,591
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	001	1	9/24/2019	NEW	$0
														Subtotal = $732,591

Grand Total All Awards = $3,443,738

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Molecular mechanisms of structural plasticity of inhibitory GABAergic interneurons

Award Number: R01MH118442

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/13/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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