ED Sciences de la Vie et de la Santé
Effects of peri-adolescent obesogenic diet on hippocampal area CA2-dependent memory and social functions.
by Alice FERMIGIER (Nutrition et Neurobiologie Intégrée)
The defense will take place at 14h00 - Bâtiment Biologie Santé (BBS) - Amphithéâtre 2, rue du Dr Hoffmann Martinot
in front of the jury composed of
- Guillaume FERREIRA - Directeur de recherche - Université de Bordeaux - Directeur de these
- Nadine RAVEL - Directrice de recherche - Centre de Recherche en Neurosciences de Lyon - Rapporteur
- Laure VERRET - Directrice de recherche - Université Toulouse III - Paul Sabatier - Rapporteur
- Lisa ROUX - Directrice de recherche - INCIA - Examinateur
- Giovanni MARSICANO - Directeur de recherche - Institut Magendie - Examinateur
- Rebecca PISKOROWSKI - Directeur de recherche - Institut de Psychiatrie et de Neurosciences de Paris - Examinateur
Juvenile obesity is a concerning public health issue associated with several cardio-metabolic comorbidities and with cognitive impairments of a yet unknown extent. Because of the abundance of energy-dense food, the worldwide prevalence of overweight and obesity among children and adolescents aged 5–19 has risen dramatically from 8% in 1990 to 20% in 2022, stressing the importance to know the cognitive consequences of such conditions. This can be modelized using lab animals, as rodents fed a high-fat high-sugar (HFHS) diet during adolescence display deficits in different memory functions such as spatial, contextual, object and social memory. Our team recently showed that HFHS diet-induced spatial, contextual and object-based memory deficits are associated with hippocampal overactivity and can be reversed by chemogenetic decrease of hippocampal pyramidal neurons activity. In this work, we focused on social memory and wondered whether alterations of specific subfields of the hippocampus could be responsible for HFHS diet-induced social memory impairments. We focused on the dorsal CA2 area of the hippocampus as it was recently demonstrated to be necessary for social memory. Using ex vivo electrophysiology in CA2 area, our collaborators in Paris (Chevaleyre-Piskorowski team) found an hyperexcitability of pyramidal cells associated with a lower oxytocin modulation in HFHS diet-fed mice. In line with this, we demonstrated that chemogenetic inactivation restricted to CA2 hippocampal pyramidal neurons as well as local CA2 injection of oxytocin reverses social memory deficit in HFHS diet-fed mice. As stress modifies social interactions and is modulated by oxytocin, we investigated in a second study the effects of HFHS diet on stress-induced changes in social orientations and the implications of the CA2 area. Acute stress (electric shock or restraint) shifts the investigation from novel to familiar social targets (decreased preference for a novel conspecific associated with increased preference for familiar social odours) in male and female mice fed a standard diet but not in HFHS diet-fed mice. These differences were not due to perceptual deficits, since animals fed a HFHS diet perfectly detected and discriminated social odours, both before and after stress, and stress increased anxiety-like behaviour and reduced locomotion in a similar manner in mice fed a standard diet and a HFHS diet. Furthermore, while calcium activity in CA2 pyramidal neurons was slightly increased during stress in mice fed both diets, calcium activity was higher in response to social odours in HFHS diet-fed mice. Finally, chemogenetic inactivation of CA2 pyramidal neurons or local CA2 injection of oxytocin both reverses HFHS diet-induced deficits in stress modulation of conspecific and social odour preferences. Altogether, these results indicate that HFHS diet impairs social memory and stress-induced changes in social preferences through an alteration of activity and oxytocinergic system in dorsal CA2 area of the hippocampus.