Role of glutamatergic neurons in the medial prefrontal cortex (mPFC) in behavioral responses triggered by aversive memory: does the hemisphere matter?

• Grant number: 23/00542-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): June 01, 2023
• Effective date (End): September 24, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Cleopatra da Silva Planeta
• Grantee: Lucas Gomes de Souza
• Supervisor: Hugo Miguel do Vale Leite Santos de Almeida
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Research place: Universidade do Minho (UMinho), Portugal
• Associated to the scholarship: 20/11827-7 - Involvement of CRFergic neurotransmission in the functional lateralization of the medial Prefrontal Cortex (mPFC) in the cardiovascular and behavioral responses observed in the contextual fear conditioning model, BP.PD

Abstract

The medial prefrontal cortex - mPFC is a limbic structure that is involved in the expression of physiological and behavioral responses to conditioned aversive stimuli, including those triggered by conditioned fear. However, the local neurochemical mechanisms in the mPFC involved in the control of responses to the conditioned fear are still poorly understood. In this sense, it is described that the mPFC is composed of about 80% of excitatory pyramidal neurons and about 20% of inhibitory interneurons and results of previous studies indicated that the right mPFC seems to be more directly related to the control of responses physiological and behavioral changes during stress situations, whereas the left mPFC would have a counter-regulatory role by inhibiting the right mPFC. Despite evidence that aversive stimuli activate neurons in the mPFC, a role for this functional lateralization mechanism with electrophysiological and chemogenetic techniques in the control of behavioral anxiety and freezing responses of the conditioned fear by the mPFC has never been reported. Thus, our hypothesis to be investigated in the present study is that the chemogenetic silencing of glutamatergic neurons in the right hemisphere of the mPFC will reduce the behavioral responses caused by conditioned fear (freezing) and in the elevated plus maze (EPM) (related behaviors to anxiety) in rats, whereas the same manipulation in the left hemisphere will potentiate such conditioned responses. (AU)