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Intersection of causal neurodevelopmental disorder risk genes, cortical circuit function, and cognitive processing required for behavioral adaptions

Award Number: R01MH096847
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Neurodevelopmental disorders (NDDs), like most neuropsychiatric disorders, are defined in general terms through cognitive impairment and behavioral alterations. Advances in genome sequencing from large patient populations has led to the identification of genes that cause complex NDDs. As a result, a major area of basic research related to NDDs is to understand how these high-impact genetic risk factors disrupt molecular and cellular mechanisms in brain cells and how these cellular alterations translate to changes in circuitry and behavior. This ongoing R01 has historically focused on the neurobiological impact of a consensus NDD risk gene, Syngap1, on the assembly and function of cortical synaptic connectivity in mice. In the current budget period, we have made progress toward understanding the extent of touch-mediated behavioral deficits and dysfunction within cortical circuitry that processes touch in the Syngap1 mouse model. The upcoming budget period seeks to understand the cause-and-effect relationships between altered assembly, function, and plasticity of cortical circuits and touch-associated behavioral maladaptations in this model. Based on mounting published and unpublished preliminary data, we will test the overarching hypothesis that Syngap1 regulates cognitive function and behavior by sculpting cortical circuits that promote tactile perception. This hypothesis is relevant to NDD etiology because altered sensory processing is a ubiquitous manifestation of NDDs, including ASD, SCZ, and ADHD. An idea gaining momentum in the field is that alterations to cognitive function and behavior are caused, at least in part, through impaired sensory processing within cortical circuits. This research topic is relevant to mental health disorders because cognitive function is a major domain of brain function and perception is a construct that defines it. However, the circuits that support perception, how they directly impact behaviors relevant to mental health disorders, and how major genetic risk factors regulate them, remains poorly understood. Aim 1 will determine how Syngap1 expression within tactile processing cortical neurons contributes to tactile learning and behavioral phenotypes in Syngap1 mice. Aim 2 studies will determine how Syngap1 regulates mesoscale cortical plasticity during tactile learning. Aim 3 is designed to provide insight into how Syngap1 expression in forebrain excitatory neurons contributes to modulation of hindbrain arousal centers that support reinforcement learning. Overall Impact: The proposed research has the potential to define cortical circuits that causally link impaired sensory processing directly to NDD-associated cognitive and behavioral impairments. Such studies are expected to inform the growing idea in the field that impaired cortical sensory processing directly leads to behavioral maladaptations common to NDDs.


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: 2025 ( Subtotal = $757,512 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	14	11/21/2024	NON-COMPETING CONTINUATION	$757,512
														Subtotal = $757,512

Issue Date FY: 2024 ( Subtotal = $891,191 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	13	11/20/2023	NON-COMPETING CONTINUATION	$802,072
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	003	13	8/15/2024	NON-COMPETING CONTINUATION	$89,119
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	12	11/3/2023	COMPETING CONTINUATION	$1,378
2024	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	11	11/3/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,378
														Subtotal = $891,191

Issue Date FY: 2023 ( Subtotal = $891,191 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	12	1/17/2023	COMPETING CONTINUATION	$187,741
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	001	12	12/20/2022	COMPETING CONTINUATION	$703,450
2023	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	000	11	12/9/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $891,191

Issue Date FY: 2022 ( Subtotal = $634,875 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	003	11	8/17/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$36,062
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Mental Health Research Grants	002	11	6/9/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$340,222
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	004	10	9/1/2022	NON-COMPETING CONTINUATION	$0
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	10	6/8/2022	NON-COMPETING CONTINUATION	-$340,222
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	10	2/15/2022	NON-COMPETING CONTINUATION	$598,813
														Subtotal = $634,875

Issue Date FY: 2021 ( Subtotal = $665,349 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	9	2/18/2021	NON-COMPETING CONTINUATION	$665,349
														Subtotal = $665,349

Issue Date FY: 2020 ( Subtotal = $665,349 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	8	2/25/2020	NON-COMPETING CONTINUATION	$665,349
														Subtotal = $665,349

Issue Date FY: 2019 ( Subtotal = $745,594 )
2019	2019	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	001	7	2/27/2019	NON-COMPETING CONTINUATION	$745,594
2019	2016	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	5	10/24/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $745,594

Issue Date FY: 2018 ( Subtotal = $860,721 )
2018	2018	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	6	5/9/2018	COMPETING CONTINUATION	$860,721
														Subtotal = $860,721

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Mental Health Research Grants	000	5	7/3/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $614,568 )
2016	2016	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	5	5/5/2016	EXTENSION WITH OR WITHOUT FUNDS	$614,568
														Subtotal = $614,568

Issue Date FY: 2015 ( Subtotal = $614,568 )
2015	2015	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	4	6/9/2015	NON-COMPETING CONTINUATION	$614,568
														Subtotal = $614,568

Issue Date FY: 2014 ( Subtotal = $614,568 )
2014	2014	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	3	6/24/2014	NON-COMPETING CONTINUATION	$614,568
														Subtotal = $614,568

Issue Date FY: 2013 ( Subtotal = $661,570 )
2013	2013	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	2	6/26/2013	NON-COMPETING CONTINUATION	$661,570
														Subtotal = $661,570

Issue Date FY: 2012 ( Subtotal = $789,981 )
2012	2012	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	001	1	9/11/2012	NEW	$0
2012	2012	SCRIPPS RESEARCH INSTITUTE-FLORIDA	10550 NORTH TORREY PINES ROAD	LA JOLLA	CA	92037	SAN DIEGO	USA	Mental Health Research Grants	000	1	9/3/2012	NEW	$789,981
														Subtotal = $789,981

Grand Total All Awards = $9,407,037

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Intersection of causal neurodevelopmental disorder risk genes, cortical circuit function, and cognitive processing required for behavioral adaptions

Award Number: R01MH096847

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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