Obesogenic diet impairs social memory through alterations of hippocampal CA2 excitability and oxytocin signaling
Abstract
While obesity induces cardio-metabolic disorders and cognitive deficits, the underlying neural mechanisms remain unexplored. In mice, exposure to an obesogenic high-fat and sugar diet (HFD) resulted in social recognition memory deficits in both males and females, a process that is dependent upon hippocampal area CA2 and oxytocin signaling. HFD-fed mice had stronger inputs onto CA2 pyramidal neurons that led to increased action potential firing, without altering intrinsic properties or inhibitory transmission. Chemogenetic CA2 pyramidal neuron inhibition in HFD-fed mice rescued social novelty discrimination, with novelty preference in males and familiarity preference in females. We also observed that HFD in both males and females impaired the ability of oxytocin receptor activation to be permissive for endocannabinoid-mediated plasticity. Furthermore, chemogenetic inhibition of CA2 pyramidal neurons rescued oxytocin-induced endocannabinoid plasticity in both HFD-fed male and female mice, whereas it prevented endocannabinoid plasticity in control diet-fed mice. In a concentration-dependent manner, oxytocin restored potentiation of excitatory responses, allowed for endocannabinoid plasticity at CA2 inhibitory synapses, and rescued social novelty discrimination in HFD-fed mice. This study uncovers mechanisms linking neuromodulation and endocannabinoid-mediated plasticity in social memory processes and reveals the deleterious consequences of an obesogenic diet on this process.
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BibTeX
@article{muller2026obesogenic,
title = {{Obesogenic diet impairs social memory through alterations of hippocampal CA2 excitability and oxytocin signaling}},
author = {Maud Muller and Alice Fermigier and Arielle Rakotonandrasana and Eva-Gunnel Ducourneau and Matteo Moschetta and Hazim Eldirdiri and Martina Radice and Pierre-Alexandre Raffaelli and Guillaume Ferreira and Vivien Chevaleyre and Rebecca A Piskorowski},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2026.117935},
url = {https://u-bordeaux.hal.science/hal-05749357v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Obesogenic diet impairs social memory through alterations of hippocampal CA2 excitability and oxytocin signaling
AU - Maud Muller
AU - Alice Fermigier
AU - Arielle Rakotonandrasana
AU - Eva-Gunnel Ducourneau
AU - Matteo Moschetta
AU - Hazim Eldirdiri
AU - Martina Radice
AU - Pierre-Alexandre Raffaelli
AU - Guillaume Ferreira
AU - Vivien Chevaleyre
AU - Rebecca A Piskorowski
PY - 2026
DA - 2026/09/14
JO - Cell Reports
DO - 10.1016/j.celrep.2026.117935
UR - https://u-bordeaux.hal.science/hal-05749357v1
AB - While obesity induces cardio-metabolic disorders and cognitive deficits, the underlying neural mechanisms remain unexplored. In mice, exposure to an obesogenic high-fat and sugar diet (HFD) resulted in social recognition memory deficits in both males and females, a process that is dependent upon hippocampal area CA2 and oxytocin signaling. HFD-fed mice had stronger inputs onto CA2 pyramidal neurons that led to increased action potential firing, without altering intrinsic properties or inhibitory transmission. Chemogenetic CA2 pyramidal neuron inhibition in HFD-fed mice rescued social novelty discrimination, with novelty preference in males and familiarity preference in females. We also observed that HFD in both males and females impaired the ability of oxytocin receptor activation to be permissive for endocannabinoid-mediated plasticity. Furthermore, chemogenetic inhibition of CA2 pyramidal neurons rescued oxytocin-induced endocannabinoid plasticity in both HFD-fed male and female mice, whereas it prevented endocannabinoid plasticity in control diet-fed mice. In a concentration-dependent manner, oxytocin restored potentiation of excitatory responses, allowed for endocannabinoid plasticity at CA2 inhibitory synapses, and rescued social novelty discrimination in HFD-fed mice. This study uncovers mechanisms linking neuromodulation and endocannabinoid-mediated plasticity in social memory processes and reveals the deleterious consequences of an obesogenic diet on this process.
SN - 2211-1247
SN - 2211-1247
ER -