Wednesday, July 23, 2025 7/23/2025

Maturation of frontal cortico-thalamic circuitry in control of social behavior

Award Number: R01MH118297
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/18/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2029

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Maturation of frontal cortico-thalamic circuitry in control of social behavior - Impaired social processing is one of key hallmarks of many neurodevelopmental and psychiatric disorders including autism spectrum disorders (ASDs). As the social deficits tend to emerge during early childhood and adolescence, characterization of developmental trajectories is vastly important for understanding and treating underlying disruptions. The objective of our study is to identify the developmental mechanisms and windows when circuits responsible for social processing are sensitive to modulation by aberrant social experience or genetic risk of disorders. Such information will point toward therapeutic targets that allow amelioration of social deficits. During the prior funding period, we demonstrated that corticothalamic projections from medial prefrontal cortex (mPFC) to paraventricular nucleus of thalamus (PVT) (mPFC->PVT), which relays signals to various components of the classical reward circuitry, is causally necessary for proper sociability, but is dysregulated by juvenile social isolation in adult mice. Our preliminary study further revealed that mPFC->PVT neurons are also dysregulated by the deletion of several ASD related genes including Fmr1. These findings prompt new pressing questions: When and how the circuit and behavior deficits emerge across development? Can these vulnerability windows serve as windows for preventing sociability deficits? Even if these windows are missed, to what extent adult amelioration is possible later in life? In this competitive renewal, we propose to address these questions by testing a hypothesis that juvenile social isolation or genetic risk of ASD (Fmr1 deletion) convergingly dysregulates the maturation of mPFC->PVT projection neurons and sociability yet differentially impact the circuit at different developmental windows. We will also test that these developmental windows of vulnerability also serve as windows for interventions to prevent sociability deficits, while adult reversal is also possible by circuit- based interventions. We will test this hypothesis by integrating techniques to measure (fiber photometry imaging, patch-clamp/ in vivo electrophysiology) and manipulate (optogenetics/chemogenetics) the activities of selective circuits during social behavior in male/female mice.


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 = $565,819 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	002	7	3/27/2025	NON-COMPETING CONTINUATION	$565,819
2025	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	001	6	2/26/2025	COMPETING CONTINUATION	$53,606
2025	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	5	2/26/2025	NON-COMPETING CONTINUATION	-$53,606
														Subtotal = $565,819

Issue Date FY: 2024 ( Subtotal = $666,017 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	6	5/28/2024	COMPETING CONTINUATION	$666,017
														Subtotal = $666,017

Issue Date FY: 2023 ( Subtotal = $496,740 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	5	6/23/2023	NON-COMPETING CONTINUATION	$496,740
														Subtotal = $496,740

Issue Date FY: 2022 ( Subtotal = $496,740 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	4	5/6/2022	NON-COMPETING CONTINUATION	$496,740
														Subtotal = $496,740

Issue Date FY: 2021 ( Subtotal = $496,740 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	3	5/5/2021	NON-COMPETING CONTINUATION	$496,740
														Subtotal = $496,740

Issue Date FY: 2020 ( Subtotal = $582,795 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	2	5/5/2020	NON-COMPETING CONTINUATION	$523,470
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	001	2	8/6/2020	SUPPLEMENT FOR EXPANSION	$59,325
														Subtotal = $582,795

Issue Date FY: 2019 ( Subtotal = $578,739 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	001	1	9/25/2019	NEW	$0
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Mental Health Research Grants	000	1	7/18/2019	NEW	$578,739
														Subtotal = $578,739

Grand Total All Awards = $3,883,590

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Maturation of frontal cortico-thalamic circuitry in control of social behavior

Award Number: R01MH118297

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/18/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2029

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