Evaluation of the role of anterior insular cortex neuronal mechanisms in modulating memory detailedness

• Grant number: 23/13705-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: April 01, 2024
• End date: March 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Ricardo Luiz Nunes de Souza
• Grantee: Lilian Liz Reis Silva
• Supervisor: Benno Roozendaal
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: Radboud University Medical Center (Radboudumc), Netherlands
• Associated to the scholarship: 20/15352-3 - Study of the role of Corticotropin Releasing Factor (CRF) neurotransmission in the insular cortex in the control of cardiovascular and anxiogenic responses to stress in rats, BP.DR

Abstract

It is well established that stressful or emotionally arousing events are remembered better than neutral events. However, much less is known to what extent they also impact the quality of these strengthened memories. As stress-induced changes particularly the quality of memory are thought to be a driving force in stress-related mental disorders, it is of critical importance to understand how stress and emotions also affect the quality of memory. A new line of research in the Roozendaal laboratory investigates the effects of the stress hormone noradrenaline (NA) on the detailedness of object recognition memory in mice. Systemic administration of the noradrenergic stimulant yohimbine given immediately after an object training experience improved later discrimination of an object that was very similar to the training object, indicative of enhanced memory for details. Further investigations revealed that post-training yohimbine administration was associated with a reduced neuronal activity in the anterior insular cortex (aIC), but an increased activity in the perirhinal cortex (PRh) during the post-learning consolidation period. The proposed experiments will determine the causal involvement of this reduction in aIC activity as well as of functional interactions of the aIC with the PRh in regulating this NA effect on memory detailedness. In a first series of experiments, I will chemogenetically manipulate aIC activity to characterize in detail the role of local GABAergic vs. glutamatergic neurons in establishing the NA effect on memory detailedness. Then, in a second series of experiments, I will elucidate the role of aIC-PRh projection neurons in establishing the NA effect on memory detailedness. The findings of these proposed experiments will be highly relevant both for our understanding of the emotional modulation of memory and for clinical contexts.