biostudies-literatureBakoyiannis IAgence Nationale de la Recherchee80388https://www.ebi.ac.uk/biostudies/studies/S-EPMC10911750biostudies-literatureUnknown13Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome when obesity occurs during adolescence, a maturational period for brain structures critical 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 (NAc) or medial prefrontal cortex (mPFC) during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normaleLifeObesogenic diet induces circuit-specific memory deficits in mice.PMC10911750ANR-14-CE13-0014 GOALANR-15-CE17-0013 OBETEENANR-16-CE37-0010 ORUPSCoutureau ETrifilieff PBakoyiannis IDucourneau EGFermigier AFerreira GN'diaye MDucroix-Crepy CBosch-Bouju CfalseObesogenic diet induces circuit-specific memory deficits in mice.Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome when obesity occurs during adolescence, a maturational period for brain structures critical 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 (NAc) or medial prefrontal cortex (mPFC) during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normal2024-01-01T00:00:00Z2024 Mar2026-07-15T16:08:55.093Z2025-04-05T11:39:00.205ZS-EPMC109117503843665310.7554/eLife.80388