Collaborative Research: Physiological and molecular control mechanisms in a socially regulated escape-circuit in cichlid fish

动物的行为，包括我们自己的行为，受到环境背景和社会互动的影响。确定潜在的细胞和生理机制是研究这些环境对行为影响的核心。该项目通过合作，多学科的方法，结合定量行为测量，体内电生理学和单细胞功能基因组学，阐明了这些机制问题。总体重点将是利用自然和实验室种群的个体差异，以确定捕食者回避行为（逃跑反应）适应性变化的神经和分子基础。具体来说，这项工作将研究产生惊吓逃避行为的m细胞系统，在非洲的波托尼星罗非鱼（一个重要的模型系统，用于研究社会地位对分子、神经内分泌和大脑细胞过程的影响，这些过程是攻击和繁殖行为的基础）。目标是(i)量化和药理学改变（使用血清素能药物）惊吓逃避行为表现的个体差异；（ii）分析m细胞的膜特性与个体激素和行为变化的关系；（iii）评估编码5 -羟色胺受体的基因活性以及单个m细胞的全基因组转录谱。虽然基本的逃逸运动模式（如逃逸潜伏期、逃逸运动学）预计不会发生变化，但在反应性（逃逸阈值）方面可能存在定量差异。这些实验将首次使解释单个神经元在生理、细胞和分子水平上的行为变化成为可能。这一新颖的建议为阐明神经可塑性提供了一个令人兴奋和独特的途径，通过对生物体和社会环境中至关重要的行为进行系统级单细胞分析。该研究项目将为阿尔伯特·爱因斯坦医学院和德克萨斯大学奥斯汀分校的高中生、本科生和研究生提供卓越的教育效益。

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.