Skip to content
DraconiticResearch
Search Sources API
220,618 studies31 sourcesUpdated 48 min ago
Peer-reviewedCC BYELife

Reduced dorsal CA1 activity limits retention of the temporal component of declarative memory in the Cntnap2 knockout mouse model of autism

  • Elise Caitlin Rawlinson1
  • Michael Hugh McCullough1
  • Azza Sellami2
  • Aline Marighetto2
  • Alice Shaam Al-Abed1
  • Nathalie Dehorter1
  1. 1Canberra
  2. 2Bordeaux
Read full textPDFDOICite

Abstract

Growing evidence implicates the hippocampus in the pathophysiology of autism spectrum disorder, particularly in the domains of social interactions and cognition. Yet, the mechanisms driving the hippocampal-dependent cognitive atypicalities in autism remain poorly defined. Here, we characterized how dysfunction of the CA1 subfield of the dorsal hippocampus drives abnormalities in critical components of declarative memory. Using trace fear conditioning in the Cntnap2 knockout mouse model of autism, we found that capabilities to retain the association of temporally distant stimuli (i.e. temporal binding) were reduced relative to wildtype mice. Fiber photometry and optogenetic experiments demonstrated that reduced CA1 activity during temporal gaps underlies this impairment, linking CA1 dysfunction to a deficit in long-term memory retention in autism. Using a relational/declarative memory task, we also revealed a deficit in flexible spatial memory, and a preferential use of egocentric learning strategy. This inflexible learning strategy resulted from an imbalance between memory system activity, promoting frontostriatal-dependent procedural learning instead of dorsal CA1/hippocampus-dependent relational/declarative memory. Overall, this study establishes dorsal CA1 dysfunction as a circuit-level mechanism underlying cognitive inflexibility in autism, providing a neurobiological framework for hippocampal-dependent memory deficits in the condition.

Related

  1. Striatal dopamine dynamics across temporal scales in brain-specific Atp2a2 heterozygous knockout mice during reward conditioning
    M. Niido, T. Yoshida, N. Isoo +3
    bioRxivPreprintCC BY-NC-NDFull textNeurosciencebioRxiv
  2. CRISPR/Cas9-mediated PD-L1 knockout reshapes temporal transcriptomic responses to PRRSV infection in porcine alveolar macrophages
    Sunirmal Sheet, Hwan-Ju Kim, Won-Il Kim +4
    PLOS OnePeer-reviewedCC BYFull textImmunologyPLOSEurope PMC
  3. Increased CA3 burst activity in Doc2α and Syt7 knockout mice
    R. J. Salaka, E. R. Chapman
    bioRxivPreprintCC BYFull textNeurosciencebioRxiv
  4. The medial temporal lobe and the retention of scene memories across a one-week delay
    Angelique I. Delarazan, Alexis N. Garcia, Ashley Huggins +1
    PsyArXivPreprintCC0Full textNeuroscienceOSF
  5. Dual-Component Nanoemulsion Containing Brugmansia suaveolens Leaf Extract and Copaiba Oil: Antimicrobial Activity and Preclinical Wound-Healing Potential
    Sandro Pinheiro da Costa, Verônica da Silva Cardoso, Alane Beatriz Vermelho +9
    Plants (Basel, Switzerland)Peer-reviewedCC BYFull textPlant biologyEurope PMC

Cite

BibTeXRIS
BibTeX
@article{rawlinson2026reduced,
  title = {{Reduced dorsal CA1 activity limits retention of the temporal component of declarative memory in the Cntnap2 knockout mouse model of autism}},
  author = {Elise Caitlin Rawlinson and Michael Hugh McCullough and Azza Sellami and Aline Marighetto and Alice Shaam Al-Abed and Nathalie Dehorter},
  journal = {ELife},
  year = {2026},
  month = oct,
  doi = {10.7554/elife.111851},
  url = {https://europepmc.org/article/PMC/PMC13661045},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Reduced dorsal CA1 activity limits retention of the temporal component of declarative memory in the Cntnap2 knockout mouse model of autism
AU  - Elise Caitlin Rawlinson
AU  - Michael Hugh McCullough
AU  - Azza Sellami
AU  - Aline Marighetto
AU  - Alice Shaam Al-Abed
AU  - Nathalie Dehorter
PY  - 2026
DA  - 2026/10/13
JO  - ELife
DO  - 10.7554/elife.111851
UR  - https://europepmc.org/article/PMC/PMC13661045
AB  - Growing evidence implicates the hippocampus in the pathophysiology of autism spectrum disorder, particularly in the domains of social interactions and cognition. Yet, the mechanisms driving the hippocampal-dependent cognitive atypicalities in autism remain poorly defined. Here, we characterized how dysfunction of the CA1 subfield of the dorsal hippocampus drives abnormalities in critical components of declarative memory. Using trace fear conditioning in the Cntnap2 knockout mouse model of autism, we found that capabilities to retain the association of temporally distant stimuli (i.e. temporal binding) were reduced relative to wildtype mice. Fiber photometry and optogenetic experiments demonstrated that reduced CA1 activity during temporal gaps underlies this impairment, linking CA1 dysfunction to a deficit in long-term memory retention in autism. Using a relational/declarative memory task, we also revealed a deficit in flexible spatial memory, and a preferential use of egocentric learning strategy. This inflexible learning strategy resulted from an imbalance between memory system activity, promoting frontostriatal-dependent procedural learning instead of dorsal CA1/hippocampus-dependent relational/declarative memory. Overall, this study establishes dorsal CA1 dysfunction as a circuit-level mechanism underlying cognitive inflexibility in autism, providing a neurobiological framework for hippocampal-dependent memory deficits in the condition.
SN  - 2050-084X
ER  -