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Homeostatic Stabilization of Neural Function in Health and Disease

Award Number: R35NS137247
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: 12/15/2024
PERIOD OF PERFORMANCE END DATE: 11/30/2032

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Homeostatic Stabilization of Neural Function in Health and Disease - ABSTRACT Homeostatic plasticity (HP) encompasses a suite of compensatory physiological processes that stabilize neural function. It is widely hypothesized that homeostatic plasticity will be linked to the cause and/or severity of neurodevelopmental disorders including autism and intellectual disability. Yet, there remains limited molecular, mechanistic information to directly connect homeostatic plasticity to neurological and neurodevelopmental disorders. We recently made two significant advances in the field. First, we provide evidence that presynaptic homeostatic plasticity (PHP) is neuroprotective in mouse models of amyotrophic lateral sclerosis (ALS). This has given rise to the concept of homeostatic neuroprotection. Second, we have established that PHP is a potent form of homeostatic plasticity expressed in the adult mouse brain, with a specific focus on hippocampus. As a consequence, we have now established a pipeline using genome-scale forward genetic screens in Drosophila to discover fundamental mechanisms of PHP. These mechanisms are then translated to the mouse neuromuscular junction and adult mouse hippocampal preparations to test conservation of function. If conserved, we determine the intersection of new homeostatic mechanisms with the pathophysiology of mouse models of neuromuscular and central degeneration including ALS and FTD. To date, all of the core molecular mechanisms necessary for PHP, first identified in Drosophila, are conserve in mice, both centrally and peripherally. We will continue to harness this highly effective strategy to identify the first positive genetic modulators of PHP, with a goal of promoting homeostatic plasticity and enhancing neurological resilience to disease. We propose that this will pave a new path toward therapeutic development based on the rational manipulation of homeostatic 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: 2026 ( Subtotal = $1,179,422 )
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/15/2025	NON-COMPETING CONTINUATION	$1,061,480
2026	2026	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/24/2026	NON-COMPETING CONTINUATION	$117,942
														Subtotal = $1,179,422

Issue Date FY: 2025 ( Subtotal = $1,174,913 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/12/2024	NEW	$1,174,913
														Subtotal = $1,174,913

Grand Total All Awards = $2,354,335

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Homeostatic Stabilization of Neural Function in Health and Disease

Award Number: R35NS137247

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: 12/15/2024

PERIOD OF PERFORMANCE END DATE: 11/30/2032

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