A molecular approach to working memory and to memory extinction in the mammalian prefrontal cortex

Abstract

I intend to delineate the role of elements of the neuronal transcriptional machinery in the process of cognitive control. Specifically, the project will be focused on the role of the cAMP responsive element (CRE) and the serum response element (SRE), in working memory (WM) and memory extinction (ME) of conditioned fear in the rat prefrontal cortex (PFC). WM can be defined as the representation of items in consciousness during experiences or just after retrieval of previously acquired memories that guide goal-oriented behavior. ME is the process by which new learning representations are acquired on the basis of preexisting ones. Blocking CRE and SRE functions in the PFC will be attained by a novel molecular technique involving microinfusion of consensus binding-site oligos fused to cell-permeable peptide carriers into the target brain area. This new system allows a precise manipulation of the location and temporal effect of the genetic inhibition. The study of the molecular substrates underlying WM and ME in the PFC can be very enlightening, since affective changes related to posttraumatic stress disorders are accompanied by cognitive dysfunction and decreased neuronal plasticity in the PFC. The main characteristic of this project is its interdisciplinary nature. My previous research was mainly focused on the pharmacological aspects of learning, and not on the regulation of the genetic information. Understanding the neural basis of behavior definitely requires a multilevel system approach. This fellowship experience will greatly enrich my genetics and molecular biology knowledge, as well as enable me to merge cognitive neuroscience with advanced molecular biology.