Biology subjects

Fermigier, A.

Publications and source records attributed to Fermigier, A..

2 recordsLinked to original sources

bioRxiv2025

Obesogenic Diet Impairs Social Memory Through Alterations of Hippocampal CA2 Excitability and Oxytocin Signaling

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.

neuroscience↗

bioRxiv2022

Obesogenic diet induces circuit-specific memory deficits in mice

Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome during adolescence, which represents a crucial period for maturation of brain structures, such as the hippocampus which are crucial for cognition. In rodent models, we recently reported that memory impairments induced by obesogenic high-fat diet (HFD) intake during the periadolescent period can be reversed by chemogenetic manipulation of the ventral hippocampus (vHPC). Here, we used an intersectional viral approach in HFD-fed male mice to chemogenetically inactivate specific vHPC efferent pathways to nucleus accumbens or medial prefrontal cortex during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normalising this activation. Inactivation of the vHPC-nucleus accumbens pathway rescued HFD-induced deficits in recognition but not location memory. Conversely, inactivation of the vHPC-medial prefrontal cortex pathway restored location but not recognition memory impairments produced by HFD. Either pathway manipulation did not affect exploration, locomotion or anxiety-like behaviour. These findings suggest that HFD intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and that targeting these overactive pathways has therapeutic potential.

neuroscience↗