Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice

Abstract

Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.

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BibTeX RIS

BibTeX

@article{thabault2026agedependent,
  title = {{Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice}},
  author = {Mathieu Thabault and Cloé Fernandes-Gomes and Cloé Alcaraz and Anaïs Balbous and Pierre-Olivier Fernagut and Laurie Galvan},
  journal = {Neurobiology of Disease},
  year = {2026},
  month = aug,
  doi = {10.1016/j.nbd.2026.107558},
  url = {https://hal.science/hal-05745385v1},
  note = {CC BY 4.0},
}

RIS

TY  - JOUR
TI  - Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice
AU  - Mathieu Thabault
AU  - Cloé Fernandes-Gomes
AU  - Cloé Alcaraz
AU  - Anaïs Balbous
AU  - Pierre-Olivier Fernagut
AU  - Laurie Galvan
PY  - 2026
DA  - 2026/08/01
JO  - Neurobiology of Disease
DO  - 10.1016/j.nbd.2026.107558
UR  - https://hal.science/hal-05745385v1
AB  - Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.
SN  - 0969-9961
SN  - 1095-953X
ER  -

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