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Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals

Award Number: R35NS116810
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: 05/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals - Project Summary Abstract: Our perceptions, behaviors, emotions, memories and intelligence depend on the appropriate synthesis and release of specific neurotransmitters in the brain. Transmitter identity is initially established by genetic programs. It has been thought that transmitters are fixed and invariant throughout life and that the plasticity of the nervous system consists largely of changes in the strength and number of synapses. We have found that experimental perturbations of spontaneous electrical activity and natural changes in sustained sensory stimuli such as ambient light or odors respecify transmitter identity in the spinal cord and brain in the developing nervous system, leading to matching changes in postsynaptic transmitter receptor specification and changes in animal behavior. Strikingly we found that transmitter switching and receptor matching also occur in the adult mammalian brain in response to sustained sensory stimuli and can regulate behavior. These discoveries contrast sharply with the general view of transmitter constancy and identify another way that the nervous system adapts to the environment. Here we describe experiments to determine how many transmitter switches are induced by a single environmental stimulus and how many brain regions are affected. There is increasing understanding that the brain is a widely linked network and that single perturbations alter activity throughout the brain. It is important to address this issue in order to understand better the basis of changes in behavior in response to the sustained stimuli that are major determinants of our conduct. A major part of our behavioral and cognitive repertoire is habitual and results from sustained experience. We will also analyze the mechanisms that promote and modulate transmitter switching. Although it is clear that neurotransmitter switching is activity- dependent, the features of activity that are necessary to achieve switching remain unknown. In the future this knowledge may have clinical utility for driving or preventing transmitter switching in patients. The immediate goals of this research are to test specific hypotheses about the effect of activity in generating a novel form of plasticity that involves changes in transmitter identity in the adult mammalian brain. The long- term goals are to understand the role of neurotransmitter switching in regulating behaviors.


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 = $710,268 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	5/13/2026	NON-COMPETING CONTINUATION	$710,268
														Subtotal = $710,268

Issue Date FY: 2025 ( Subtotal = $709,448 )
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	8/19/2025	SUPPLEMENT FOR EXPANSION	$156,448
2025	2025	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	5/29/2025	NON-COMPETING CONTINUATION	$553,000
														Subtotal = $709,448

Issue Date FY: 2024 ( Subtotal = $536,409 )
2024	2024	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	5/1/2024	NON-COMPETING CONTINUATION	$536,409
														Subtotal = $536,409

Issue Date FY: 2023 ( Subtotal = $553,000 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/1/2023	NON-COMPETING CONTINUATION	$553,000
														Subtotal = $553,000

Issue Date FY: 2022 ( Subtotal = $553,000 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/6/2022	NON-COMPETING CONTINUATION	$553,000
														Subtotal = $553,000

Issue Date FY: 2021 ( Subtotal = $552,715 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/26/2021	NON-COMPETING CONTINUATION	$539,538
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	9/15/2021	NON-COMPETING CONTINUATION	$13,177
														Subtotal = $552,715

Issue Date FY: 2020 ( Subtotal = $551,250 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/29/2020	NEW	$551,250
														Subtotal = $551,250

Grand Total All Awards = $4,166,090

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Determining Fundamental Properties of Neurotransmitter Switching in Adult Mammals

Award Number: R35NS116810

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: 05/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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