Saturday, July 5, 2025 7/5/2025

Investigating mechanisms underlying impaired social and spatial cognition in rodent models of Fragile X syndrome

Award Number: R01MH131317
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2022
PERIOD OF PERFORMANCE END DATE: 05/31/2026

Group Awards By:

View Award Description

Investigating mechanisms underlying impaired social and spatial cognition in rodent models of Fragile X syndrome - Project Summary/Abstract. Fragile X syndrome (FX) is a widespread type of inherited intellectual disability. Effective treatments that target mechanisms underlying FX are currently lacking. FX is the foremost monogenic cause of autism spectrum disorders, and thus many individuals with FX exhibit abnormal social behaviors. Individuals with FX also often engage in aberrant spatial behaviors such as “elopement”, wandering off and getting lost. The hippocampus is a brain structure that is particularly vulnerable to FX. Much evidence suggests that hippocampal areas CA2 and CA1 are important for social behaviors and spatial memory, respectively. Yet, few studies have investigated whether disturbances in neurophysiological mechanisms in CA2 and CA1 could underlie impaired social and spatial cognitive functioning in FX. This project’s goal is to address this gap in knowledge by investigating the extent to which subcellular, cellular, circuit, and neuronal population mechanisms of social and spatial memory operations in the hippocampus are impaired in rodent models of FX. The studies will employ state-of-the-art in vivo and in vitro electrophysiological techniques. In vivo approaches will be used to assess whether impairments in cellular responses in CA2 and coordinated neuronal population activity in CA1 could explain deficits in social and spatial cognition in FX. In vitro experiments will be conducted to uncover cellular mechanisms underlying altered intrinsic properties of and plasticity in CA2 neurons and aberrant inhibitory circuits in CA1. Models of FX in two species, specifically Fmr1 knockout (KO) rats and mice, will be used, allowing comparison of FX pathophysiology across species. Specific Aim 1 will assess whether correlated neuronal spiking activity between CA2 and one of its major inputs, CA3, is weaker in Fmr1 KO rats than wildtype rats during exploration of social stimuli. Specific Aim 2 will employ whole cell and patch clamp recordings, including recordings directly from dendrites, in hippocampal slices to test whether CA2 neurons in Fmr1 KO rats and mice show impaired synaptic plasticity and deficient responses to the social neuropeptide, oxytocin. Specific Aim 3 will test whether reactivation, or “replay”, of spike sequences from populations of CA1 neurons that code for previously learned spatial trajectories is disrupted in Fmr1 KO rats. Replay is critical for spatial memory operations, and thus disrupted replay could contribute to impaired spatial cognition and behavior in FX. Replay of CA1 neuronal spike sequences is temporally coordinated by properly timed activation of specific CA1 inhibitory interneurons. Thus, disrupted replay of CA1 spike sequences in FX may reflect disturbances in CA1 inhibitory circuits. Specific Aim 4 will employ whole cell recordings from CA1 pyramidal neurons, specific classes of CA1 interneurons, and connected CA1 interneuron-pyramidal cell pairs to test the hypothesis that inhibitory circuits are disrupted in FX. Successful completion of these Aims will provide novel insights about specific mechanisms underlying aberrant social and spatial cognition and behaviors in FX. Gaining a deeper understanding of FX mechanisms is expected to suggest novel targets for intervention in FX.


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 = $743,688 )
2025	2025	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	4	5/28/2025	NON-COMPETING CONTINUATION	$743,688
														Subtotal = $743,688

Issue Date FY: 2024 ( Subtotal = $764,933 )
2024	2024	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	3	5/30/2024	NON-COMPETING CONTINUATION	$764,933
														Subtotal = $764,933

Issue Date FY: 2023 ( Subtotal = $764,933 )
2023	2023	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	2	5/25/2023	NON-COMPETING CONTINUATION	$764,933
														Subtotal = $764,933

Issue Date FY: 2022 ( Subtotal = $773,650 )
2022	2022	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR	AUSTIN	TX	78712	TRAVIS	USA	Mental Health Research Grants	000	1	8/1/2022	NEW	$773,650
														Subtotal = $773,650

Grand Total All Awards = $3,047,204

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating mechanisms underlying impaired social and spatial cognition in rodent models of Fragile X syndrome

Award Number: R01MH131317

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2022

PERIOD OF PERFORMANCE END DATE: 05/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer