Venue: BBS
Defense in french
Alice Fermigier
NutriNeuro
Thesis supervisor: Guillaume Ferreira
Title
Effect of obesogenic food consumption on memory and social functions: implication of hippocampal area CA2
Abstract
Childhood obesity is a concerning public health issue associated with cardiometabolic co- morbidities, but also with cognitive deficits whose extent remains poorly understood. Due to increasing consumption of obesogenic foods, the worldwide prevalence of overweight and obesity in children and adolescents aged 5 to 19 has risen considerably, from 8% in 1990 to 20% in 2022, hence the importance of knowing their cognitive consequences. Juvenile obesity be modeled with rodents fed a diet high in saturated fat and sugar (HFD) during adolescence. Our team has recently shown that HFD-induced deficits in spatial, contextual and object recognition memory are associated with hippocampal hyperactivity and can be restored by chemogenetically decreasing the activity of hippocampal pyramidal neurons. In this thesis work, we sought to decipher whether specific areas of the hippocampus might be responsible for alterations in social memory in particular. We focused on the CA2 area of the dorsal hippocampus, known for its crucial role in social memory.
Ex vivo electrophysiological approaches carried out by the Chevaleyre-Piskorowski team revealed hyperexcitability of CA2 pyramidal cells, associated with reduced oxytocinergic modulation in HFD-fed mice. In parallel, we showed that chemogenetic inactivation restricted to CA2 pyramidal neurons and local injection of oxytocin in CA2 reversed social memory deficits in HFD-fed mice.
Stress also influences social interactions. So, in a second study, we assessed the impact of a HFD on this modulation of social orientations by stress, and the role played by area CA2. Acute stress (electric shock or restraint) decreases the investigation of novel social targets, leading to decreased preference for a novel conspecific and increased preference for familiar social odors, and thus in control diet but not HFD-fed mice. This lack of stress-induced social neophobia in HFD-fed mice is associated with greater basal calcium activity in CA2 pyramidal neurons. Furthermore, chemogenetic inactivation of these neurons or local injection of oxytocin into CA2 restored stress-induced social neophobia in HFD-fed mice. Altogether, our results show that HFD feeding during adolescence disrupts social memory and stress-induced social neophobia by altering the activity and the oxytocinergic system in the CA2 area of the hippocampus.
Keywords: obesity, social memory, social preferences, stress, adolescence, CA2, hippocampus, oxytocin, chemogenetics
Publications
Fermigier A., Ferreira G. (2021). Neurobiologie des apprentissages alimentaires. La Lettre des Neurosciences 61 20-23
Bakoyiannis I., Ducourneau E.G., N’Diaye M., Fermigier A., Ducroix-Crepy C., Fauré L., Bosch- Bouju C., Coutureau E., Trifilieff P., Ferreira G. (2024) Obesogenic diet induces circuit-specific memory deficits in mice. eLife 4:13:e80388. doi :10.7554/eLife.80388
Fermigier A., Ducourneau E.G., Potier M., Helbling J.C., Bakoyiannis I., Chevaleyre V., Piskorowski R.A., Ferreira G. (in preparation) Obesogenic diet impairs social responses to stress through hippocampal CA2 dysfunction: emphasis on oxytocin signaling
Muller M., Fermigier A., Ducourneau E.G., Potier M., Helbling J.C., Ferreira G., Piskorowski R.A., Chevaleyre V. (in preparation) A high-fat diet impairs social memory through aberrant hippocampal CA2 excitability and oxytocin signaling
Jury
- Nadine RAVEL, DR, CNRS, Université Lyon I – Rapportrice
- Laure VERRET, Maître de Conférences, CNRS, Université Toulouse III – Rapportrice
- Lisa ROUX, DR, CNRS, INCIA (Bordeaux) – Examinatrice
- Giovanni MARSICANO, DR, INSERM, Institut Magendie (Bordeaux) – Examinateur
- Rebecca PISKOROWSKI, DR, INSERM, Institut de Psychiatrie et de Neurosciences (Paris) – Examinatrice