Neuroepigenetic mechanisms underlying intergenerational inheritance of negative emotional states

• Grant number: 17/50014-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2017
• End date: October 31, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Emory University
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Newton Sabino Canteras
• Grantee: Newton Sabino Canteras
• Principal researcher abroad: Brian George Dias
• Institution abroad: Emory University, United States
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 14/05432-9 - Neural bases of fear and aggression, AP.TEM

Abstract

Olfactory fear conditioning is a powerful and innovative framework to model intergenerational stress because it allows us to "tag" a stressor in one generation (odor + US) and then follow the tag (odor) in the future offspring at the level of structure (visualize olfactory neurons), function (flow of olfactory information from the periphery into the central nervous system), and genetics (loci encoding specific odorant receptors). Brian Dias has used olfactory fear conditioning in an inter-generational context and reported that conditioning a paternal generation of mice (FO) resulted in F1 offspring of FO conditioned males being able to detect lower concentrations of the FO conditioned odor (behavioral sensitivity). We have two aims in this project. The first aim is to determine the neural circuitry in offspring triggered by olfactory stressors present only in the parental environment. Thus, combining detailed behavioral analysis and c-fos based mapping of activity in the brain, we shall characterize putative correlations between dPAG activity and any particular type of defensive or fearful behavior in the F1 mice once they detect the odor that was used to condition the FO parent. The second aim is to determine the epigenetic mechanisms altered in the brains of offspring born to parents exposed to olfactory stress. In this study, we shall characterize the regulation of gene expression in the F1 mice once they detect the odor that was used to condition the FO parent. (AU)