In addition to numerous metabolic comorbidities, obesity is associated with several adverse neurobiological outcomes, especially learning and memory alterations. Obesity prevalence is rising dramatically in youth and is persisting in adulthood. This is especially worrying since adolescence is a crucial period for the maturation of certain brain regions playing a central role in memory processes such as the hippocampus and the amygdala. We previously showed that periadolescent, but not adult, exposure to obesogenic high-fat diet (HFD) had opposite effects on hippocampus- and amygdala-dependent memory, impairing the former and enhancing the latter. However, the causal role of these two brain regions in periadolescent HFD-induced memory alterations remains unclear. Here, we first showed that periadolescent HFD induced long-term, but not short-term, object recognition memory deficits, specifically when rats were exposed to a novel context. Using chemogenetic approaches to inhibit targeted brain regions, we then demonstrated that recognition memory deficits are dependent on the activity of the ventral hippocampus, but not the basolateral amygdala. On the contrary, the HFD- induced enhancement of conditioned odor aversion specifically requires amygdala activity. Taken together, these findings suggest that HFD consumption throughout adolescence impairs long-term object recognition memory through alterations of ventral hippocampal activity during memory acquisition. Moreover, these results further highlight the bidirectional effects of adolescent HFD on hippocampal and amygdala functions.
The microscopy was completed at the Bordeaux Imaging Center, a service unit of CNRS-INSERM and Bordeaux University and member of the national infrastructure, France BioImaging. We thank María José Olvera for technical assistance and Yoan Salafranque for the care provided to the animals during experiments.
FUNDING AND DISCLOSURE:
OBETEEN consortium received financial support by the French National Research Agency (Agence Nationale de la Recherche: ANR) by the grant No. ANR-15-CE17-0013 and the Mexican National Council for Science and Technology (Consejo Nacional de Ciencia y Tecnología: CONACYT) by the grant No. 273553. This work was also supported by INRA (to G.F.), CNRS (to E.C.), and French National Research Agency (ANR-14-CE13-0014 GOAL to E.C. and G.F.; ANR-16-CE37-0010 ORUPS to G.F.). F.N. was recipient of a postdoctoral fellowship from ANR OBETEEN (2015–2016), I.B. is the recipient of a PhD fellowship from the French Ministry of Research and Higher Education (2018-2021) and M.S.Z. is the recipient of a PhD fellowship from CONACYT (2017-2019). The authors declare no conflict of interest.