Animal behavior, including our own, is influenced by environmental context and social interactions. Determining the underlying cellular and physiological mechanisms is central in studying these environmental effects on behavior. This project elucidates such mechanistic questions through a collaborative, multidisciplinary approach that merges quantitative behavioral measurements, in vivo electrophysiology, and single cell functional genomics. The overall focus will be on exploiting individual variation in natural and laboratory populations in order to determine the neuronal and molecular basis of adaptive changes of predator avoidance behavior (escape response). Specifically, the work will study the M-cell system, which generates startle escape behavior, in the African cichlid fish Astatotilapia burtoni (an important model system for investigating the influence of social rank on the molecular, neuroendocrine and cellular processes in the brain that underlie aggressive and reproductive behaviors). The goal is to (i) quantify and pharmacologically alter (using serotonergic drugs) individual differences in the performance of startle escape behavior; (ii) analyze the membrane properties of the M-cell in their relationship to individual variation in hormones and behavior; (iii) assess the activity of genes encoding serotonin receptors as well as genome-wide transcript profiles from single M-cells. While the essential escape motor pattern (e.g. escape latency, escape kinematics) is not expected to vary, quantitative differences in responsiveness (escape thresholds) are likely. These experiments will for the first time make it possible to explain variation in behavior at the physiological, cellular and molecular levels in a single neuron. This novel proposal provides an exciting and unique avenue for elucidating neural plasticity through a systems-level single-cell analysis of a vitally important behavior within an organismic and social context. This research project will provide outstanding educational benefits to high school students, undergraduate and graduate students at the Albert Einstein College of Medicine and at The University of Texas at Austin.