A major goal of neuroscience research is to understand the molecular-genetic specification of behaviors and how the environment influences these mechanisms. Lack of knowledge of these molecular-genetic mechanisms is a major barrier to progress, as this limits knowledge about the interplay between nuclear, synaptic and physiological neuronal functions that direct behaviors and plasticity. Understanding the molecular- genetic mechanisms that drive complex behaviors in model systems is an important step. We propose a collaborative and unique approach to address our lack of understanding of complex behaviors. This study will be one of the first to examine on a genome-wide scale several molecular phenotypes that drive complex behaviors. We propose to use state-of-the-art tools, which are newly developed by our laboratory, to examine at a cell-specific level several molecular phenotypes. We will examine chromatin, transcription factor binding, gene expression and alternative pre-mRNA splicing in neural circuits that are well defined and known to underlie behavior. This innovative approach will allow us to identify the molecular process that are required to drive the potential and maintenance of this behavior, by examining these phenotypes during development and adult stages. In addition, we examine how the environment can modify behavior by examining the molecular and neural circuit basis of long-term memory formation. The project will be the first to elucidate and integrate, in a cell-specific manner, several molecular phenotypes that direct complex behavior, including how sex- differences in the molecular environment influence behavior. We will statistically integrate knowledge of all of these phenotypes to gain insights into the complex interplay between environment, molecular, neural circuit and behavioral phenotypes.
Many human disorders, including mental health and behavioral disorders, are caused by defects in basic molecular processes. While our fundamental understanding of basic molecular biology has vastly increased, very little is known at a molecular-genetic level regarding the impact of defects in molecular processes on complex behavior. This study will provide a foundation to begin to understand the complex biological mechanisms that contribute to the potential to perform complex behaviors, the influence of the environment and how defects in these biological processes cause human health disorders.
