To understand how memory is regulated at the molecular level, it is better first to focus on a simple behavior, controlled by well described neuronal connections. Memory of learned fear is well suited for this purpose, as it can be studied by a relatively simple Pavlovian fear conditioning, for which anatomic connections in the brain are well defined. The goal of this project is to unravel how gene regulatory networks, uniquely localized to the neural circuits of learned fear, control fear memory. This new researcher has recently identified a gene, encoding gastrin-releasing peptide (Grp), as being highly present in a limited population of neurons in learned fear circuitry and specifically in the amygdala, a key brain area involved in fear and emotion. Using gene knockout approach, the researcher will explore how the elimination of the Grp gene in mice (gene knockout) affects learned fear. Next, using a transgenic approach the researcher will examine the result of the elimination of neurons that express the Grp gene. Finally, the possibility that cells expressing this gene are specifically activated by fear experience will be analyzed. It is expected that this study will characterize a unique population of GRP-expressing neuronal cells involved in fear memory formation. The results obtained in the course of this work are applicable to other brain networks as well; they will guide future efforts to examine the emerging principles of how genes control brain-behavior link and to ask questions and create models for the Systems Biology approach. Thus, this work highlights important principles of how gene regulatory networks control stress-induced remodeling, which alters behavioral and physiological responses to adapt to potentially threatening environment and therefore produces multi-level resilience to stress exposure in animals and as well as other organisms. The broader impacts of this award include progress in our understanding of how learning and memory allow organisms to adapt to environments in the presence of risk and danger. The award will pave the way to an understanding of innate behaviors critical for survival. Additionally, this award will allow the researcher to use his laboratory as a training ground for undergraduates who in the future will go on to careers studying the genetics of learning, memory and behavior.
