Involvement of prefrontal cortex areas and their targets in fear memory processing: a study with drug and optogenetic techniques

• Grant number: 16/10389-0
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2016
• Effective date (End): September 30, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Newton Sabino Canteras
• Grantee: Miguel Antonio Xavier de Lima
• 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

We have recently shown that inactivation of the ventral part of the anteromedial thalamic nucleus (AMv) impairs the acquisition of predator-related contextual fear memory acquisition. We have further shown that cytotoxic lesions in medial prefrontal cortical areas (PFM) targeted by AMv (i.e., the prelimbic (PL) and anterior cingulate areas (ACA)) also impair the predator-related fear memory processing. In the present proposal, first, we will investigate whether the PL and ACA influence the acquisition of predator-related fear memory by inactivating these cortical fields during predator exposure using farmacogenetic tools with adeno-associated virus (AAV) expressing hM4D receptors (assay 1). Next, we will investigate the projection of the PL and ACA neurons particularly activated during the acquisition of fear memory. To this end, we will use genetically modified Cre inducible Fos mouse, which will receive in the PL or ACA injections of Cre-dependent AAV to express synaptobrevin in presynaptic terminals of Fos-positive neurons during the predator exposure (assay 2). Once mapped the active projections from PL and ACA areas during predator exposure, we will investigate which ones are involved in the acquisition of fear memory by using viral tools to induce the expression of halorhodopsin channels in these areas and their terminal fields, and thus inhibit optogenetically the terminal fields previously found to be particularly mobilized during the acquisition of fear memory (assay 3). We will be able to establish which pathways from the PFM are critically involved in the acquisition of the predator-related fear memory. In this project, we will use the state of the art viral tools to understand how the PFM should be involved in the acquisition of fear memory in the predator exposure paradigm, which is one of the most reliable behavioral approach to reproduce residual systemic symptoms observed in patients with post-traumatic stress disorders. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RUFINO, RODRIGO DE ANDRADE; MOTA-ORTIZ, SANDRA REGINA; XAVIER DE LIMA, MIGUEL ANTONIO; BALDO, MARCUS VINICIUS C.; CANTERAS, NEWTON SABINO. The rostrodorsal periaqueductal gray influences both innate fear responses and acquisition of fear memory in animals exposed to a live predator. Brain Structure & Function, v. 224, n. 4, p. 1537-1551, MAY 2019. (14/02540-5, 14/05432-9, 16/10389-0)

XAVIER DE LIMA, MIGUEL ANTONIO; BALDO, MARCUS VINICIUS C.; CANTERAS, NEWTON SABINO. Revealing a Cortical Circuit Responsive to Predatory Threats and Mediating Contextual Fear Memory. CEREBRAL CORTEX, v. 29, n. 7, p. 3074-3090, JUL 2019. (14/05432-9, 16/10389-0)

XAVIER DE LIMA, MIGUEL ANTONIO; BALDO, MARCUS VINICIUS C.; OLIVEIRA, FERNANDO A.; CANTERAS, NEWTON SABINO. The anterior cingulate cortex and its role in controlling contextual fear memory to predatory threats. eLIFE, v. 11, JAN 5 2022. (14/05432-9, 16/10389-0, 19/27245-0)