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Synaptic plasticity across the lifespan

Award Number: R01MH095980
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/09/2012
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Synaptic plasticity across the lifespan - The overall goal is to understand synaptic mechanisms of learning and memory. Long-term potentiation (LTP) is a model of learning and memory that is well-suited to investigate these processes. Dendritic spines host about ninety percent of excitatory synapses in the brain and are well known to show structural plasticity following induction of LTP. The developmental onset of dendritic spines coincides with an abrupt developmental onset for LTP lasting more than three hours (L-LTP) at postnatal day 12 (P12) in rat hippocampus. At P10 and P15, LTP enhances synaptogenesis and small spine formation. With maturation, the LTP-accelerated synaptogenesis shifts to a process that enlarges specific synapses and retains spine clusters locally but is balanced by reduction in spine numbers elsewhere on the dendrite. The spine clusters are locally delimited by the availability of smooth endoplasmic reticulum (SER), an organelle critical for regulating calcium, and the transport of lipids and proteins, and by the presence of polyribosomes, which mediate local protein synthesis. The LTP-produced synapse enlargement is greatest on spines that contain a spine apparatus, which is a structure derived from SER that provides synthesis and post-translational modification of transmembrane proteins. Structural changes in presynaptic axons are also developmentally regulated following LTP and mirror the spine changes with new boutons forming to accommodate the LTP-accelerated synaptogenesis at P15, and fewer boutons occurring with spine reduction at P60. Thus, LTP in developing hippocampus accelerates synaptogenesis, whereas resource-dependent synapse growth and spine clustering occur on mature dendrites. This homeostatic balance in synaptic plasticity is hypothesized to be disrupted with cognitive decline in the aging brain. A comprehensive analysis of structural synaptic plasticity during maturation and senescence is proposed as a foundation for understanding lifelong changes in cognitive capacity. Specifically, the aims are: Aim 1: Evaluate the maturation of resource-dependent synaptic growth and clustering. Aim 2: Determine circuit generality and synapse specificity of resource-dependent growth and clustering. Aim 3: Determine synaptic foundation of cognitive capacity and decline in the aging hippocampus. Aim 4: Test importance of the spine apparatus in synapse growth and clustering. Outcomes promise essential insight into the synaptic basis of learning and memory across lifespan and will provide basic knowledge that could inform new therapies for developmental and age-related brain disorders.


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 )
2026	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	9	11/20/2025	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2023 ( Subtotal = $565,538 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	9	6/20/2023	NON-COMPETING CONTINUATION	$565,538
														Subtotal = $565,538

Issue Date FY: 2022 ( Subtotal = $575,202 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	8	6/13/2022	NON-COMPETING CONTINUATION	$575,202
														Subtotal = $575,202

Issue Date FY: 2021 ( Subtotal = $669,550 )
2021	2021	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	002	7	6/10/2021	NON-COMPETING CONTINUATION	$565,538
2021	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	001	6	3/16/2021	COMPETING CONTINUATION	$117
2021	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	6	3/4/2021	COMPETING CONTINUATION	$103,894
														Subtotal = $669,550

Issue Date FY: 2020 ( Subtotal = $667,816 )
2020	2020	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	6	6/15/2020	COMPETING CONTINUATION	$667,816
														Subtotal = $667,816

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2016	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	5	8/29/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $375,895 )
2016	2016	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Mental Health Research Grants	000	5	5/4/2016	EXTENSION WITH OR WITHOUT FUNDS	$375,895
														Subtotal = $375,895

Issue Date FY: 2015 ( Subtotal = $375,895 )
2015	2015	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Mental Health Research Grants	000	4	6/9/2015	NON-COMPETING CONTINUATION	$375,895
														Subtotal = $375,895

Issue Date FY: 2014 ( Subtotal = $375,895 )
2014	2014	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Mental Health Research Grants	000	3	6/21/2014	NON-COMPETING CONTINUATION	$375,895
														Subtotal = $375,895

Issue Date FY: 2013 ( Subtotal = $360,674 )
2013	2013	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Mental Health Research Grants	000	2	6/25/2013	NON-COMPETING CONTINUATION	$360,674
														Subtotal = $360,674

Issue Date FY: 2012 ( Subtotal = $374,740 )
2012	2012	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Mental Health Research Grants	000	1	7/10/2012	NEW	$374,740
														Subtotal = $374,740

Grand Total All Awards = $4,341,204

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Synaptic plasticity across the lifespan

Award Number: R01MH095980

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/09/2012

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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