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Circuit Defects Underlying Deficits in Social Touch in Fragile X Syndrome

Award Number: R01HD054453
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Circuit Defects Underlying Deficits in Social Touch in Fragile X Syndrome - ABSTRACT Sensory hypersensitivity and the resulting avoidance behaviors represent a major challenge for most individuals with Fragile X syndrome (FXS) and for many autistic people. Differences in sensory processing can also contribute to inattention/distraction, learning disability, repetitive behaviors, and even social avoidance. Indeed, exaggerated responses to tactile stimuli could also worsen anxiety about social interactions, especially if they involve physical contact (e.g., shaking hands, hugging, kissing) and if the contact is unwanted. For this proposal we will explore this relationship between sensory hypersensitivity and social experience in FXS/autism. Social touch per se has not been investigated in animal models of autism, including FXS; therefore, it is presently unknown whether they display unique avoidance behaviors or aversive facial expressions to different types of social touch. It is also not known how such maladaptive behaviors to social touch might be represented in neural dynamics of relevant brain areas. To address these knowledge gaps, we have developed a novel assay for social touch in mice. We previously demonstrated that Fmr1-/- mice, the main model of FXS, show avoidance and defensive behaviors to repetitive whisker stimulation, akin to tactile defensiveness in humans with FXS. In more recent studies we have shown that Fmr1-/- mice and maternal immune activation (MIA) model mice both show strikingly similar behavioral phenotypes in response to repeated bouts of social touch, including hyperarousal, running avoidance, and sustained eye closure. Here, we will follow a symptom-to-circuit strategy to better understand social touch deficits in FXS/autism. First, we will characterize behavioral responses to social touch in Fmr1-/- and MIA mice with our novel behavioral assay we have developed. Second, we will `reverse- engineer' such phenotypes by identifying the underlying circuit and neuronal changes using in vivo electrophysiological recordings with Neuropixels probes. Finally, we will intervene at the level of neuronal activity in the relevant circuits (focusing on somatosensory cortex and amygdala) with pharmacology and chemogenetics, to mitigate deficits in social touch. Our hope is that these preclinical studies will yield significant insights for the treatment of FXS/autism.


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 = $431,582 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	002	17	4/24/2025	NON-COMPETING CONTINUATION	$431,582
2025	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	16	3/20/2025	COMPETING CONTINUATION	$30,516
2025	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	15	3/20/2025	NON-COMPETING CONTINUATION	-$30,516
														Subtotal = $431,582

Issue Date FY: 2024 ( Subtotal = $426,841 )
2024	2024	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	16	7/25/2024	COMPETING CONTINUATION	$426,841
														Subtotal = $426,841

Issue Date FY: 2023 ( Subtotal = $324,870 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	15	5/15/2023	NON-COMPETING CONTINUATION	$324,870
														Subtotal = $324,870

Issue Date FY: 2022 ( Subtotal = $324,870 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	14	5/10/2022	NON-COMPETING CONTINUATION	$324,870
														Subtotal = $324,870

Issue Date FY: 2021 ( Subtotal = $324,870 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	13	4/15/2021	NON-COMPETING CONTINUATION	$324,870
														Subtotal = $324,870

Issue Date FY: 2020 ( Subtotal = $331,500 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	12	4/9/2020	NON-COMPETING CONTINUATION	$331,500
														Subtotal = $331,500

Issue Date FY: 2019 ( Subtotal = $331,500 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	11	1/9/2019	COMPETING CONTINUATION	$331,500
2019	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	10	7/31/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $331,500

Issue Date FY: 2018 ( Subtotal = $319,550 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	10	4/27/2018	NON-COMPETING CONTINUATION	$319,550
														Subtotal = $319,550

Issue Date FY: 2017 ( Subtotal = $319,550 )
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	9	6/22/2017	NON-COMPETING CONTINUATION	$31,955
2017	2017	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	9	5/11/2017	NON-COMPETING CONTINUATION	$287,595
														Subtotal = $319,550

Issue Date FY: 2016 ( Subtotal = $316,354 )
2016	2016	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	8	4/6/2016	NON-COMPETING CONTINUATION	$316,354
														Subtotal = $316,354

Issue Date FY: 2015 ( Subtotal = $311,560 )
2015	2015	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	7	4/10/2015	NON-COMPETING CONTINUATION	$311,560
														Subtotal = $311,560

Issue Date FY: 2014 ( Subtotal = $319,550 )
2014	2014	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	6	4/16/2014	COMPETING CONTINUATION	$319,550
														Subtotal = $319,550

Issue Date FY: 2012 ( Subtotal = $0 )
2012	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	5	4/13/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $254,086 )
2011	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	5	4/5/2011	NON-COMPETING CONTINUATION	$286,676
2011	2011	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	002	5	6/9/2011	NON-COMPETING CONTINUATION	$19,112
2011	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	4	11/24/2010	NON-COMPETING CONTINUATION	-$51,702
														Subtotal = $254,086

Issue Date FY: 2010 ( Subtotal = $522,622 )
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	4	4/19/2010	NON-COMPETING CONTINUATION	$402,471
2010	2010	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Trans-NIH Recovery Act Research Support	001	4	7/7/2010	SUPPLEMENT FOR EXPANSION	$120,151
														Subtotal = $522,622

Issue Date FY: 2009 ( Subtotal = $406,536 )
2009	2009	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	3	4/3/2009	NON-COMPETING CONTINUATION	$406,536
														Subtotal = $406,536

Issue Date FY: 2008 ( Subtotal = $383,837 )
2008	2008	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	11000 KINROSS AVENUE	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	2	4/21/2008	NON-COMPETING CONTINUATION	$383,837
														Subtotal = $383,837

Issue Date FY: 2007 ( Subtotal = $391,670 )
2007	2007	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	001	1	4/18/2007	SUPPLEMENT FOR EXPANSION	$86,520
2007	2007	UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS	10920 WILSHIRE BLVD, 5TH FLOOR	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	3/19/2007	NEW	$305,150
														Subtotal = $391,670

Grand Total All Awards = $6,041,348

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Circuit Defects Underlying Deficits in Social Touch in Fragile X Syndrome

Award Number: R01HD054453

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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