Document Type

Article

Publication Date

5-8-2025

Keywords

JMG, Animals, Fragile X Syndrome, Hippocampus, Rats, Disease Models, Animal, Male, Prefrontal Cortex, Behavior, Animal, Nerve Net, Social Behavior, Anxiety, Action Potentials, Fragile X Mental Retardation Protein

JAX Source

Sci Rep. 2025;15(1):16089.

ISSN

2045-2322

PMID

40341845

DOI

https://doi.org/10.1038/s41598-025-99408-8

Grant

This work received funding from the Swank Foundation, R21NS117112 (RS) and start-up funds from the Ne- mours Foundation.

Abstract

Fragile X Syndrome (FXS) is a common cause of autism spectrum symptoms. The genetic mutation results in multiple molecular alterations that are hypothesized to negatively impact neural circuit development although the nature of any functional neural dynamic consequences remain unclear. Therefore, the characteristics of hippocampal-prefrontal (H-PFC) network dysfunction were investigated in a rat model of FXS. FMR-KO and control rats underwent behavioral tests assessing sociability, memory, and anxiety to validate and replicate previously recognized deficits. Single-unit electrophysiology in the H-PFC circuit during exploration was used to measure patterns of action potential firing that were then compared between groups using generalized linear mixed models. FMR-KO rats demonstrated significant behavioral deficits in sociability, spatial learning, and anxiety. These rats also exhibited abnormal firing patterns outside of times when specific behavioral tasks were being performed. The network firing is less precise, more fragmented and with poor H-PFC communication in FXS. These findings suggest that disruptions in 'exploration' neural network dynamics impair the ability of networks to be appropriately engaged during specific behavioral tasks, leading to the observed deficits in social behavior, memory, and anxiety.

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