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

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)