The role of the zebrafish spaced out gene in modulating startle behavior

描述（由申请人提供）：惊吓反射，像大多数运动行为一样，可以根据环境条件进行运动学调节。虽然这种调节在各种神经系统疾病中被破坏，但脊椎动物中这些破坏的遗传基础仍然知之甚少。我将专注于从运动缺陷基因筛选中分离出来的一个基因（分隔开），这是惊吓反射调制所特别需要的。当这个基因被破坏时，个体就会启动一种夸张的、不协调的反应。我将通过斑马鱼的遗传、行为、细胞标记和电生理方法揭示关键脊椎动物惊吓反应回路的神经和遗传调控。我的三个具体目标是：1)识别和描述间隔基因，从而识别控制惊吓反应的脊椎动物神经回路的遗传调节器。这些实验将揭示这个关键基因在神经发育和功能过程中的时间和空间要求。2)确定间隔基因在惊吓行为调节中的作用，揭示该基因在调节各种情况下协调和调节特定运动模式的神经元群中的作用范围和特异性。这些实验将测试脊椎动物神经回路中调节不同运动行为的重叠程度。3)表征由间隔调节的惊吓行为的神经元，详细描述惊吓回路神经成分之间的神经活动和突触连接模式。这些实验将揭示在惊吓反射过程中，关键突触连接的发展和关键神经元的活动都需要间隔。完成这些目标将阐明脊椎动物惊吓反射运动的神经调节的遗传基础。

DESCRIPTION (provided by applicant): Startle reflexes, like most motor behaviors, can be kinematically modulated in response to environmental conditions. While this modulation is disrupted in a variety of neurological disorders, the genetic bases for these disruptions in vertebrates remain poorly understood. I will focus on a gene (spaced out) isolated from a genetic screen for locomotor defects, which is specifically required for startle reflex modulation. When this gene is disrupted, individuals initiate an exaggerated and improperly coordinated response. I will uncover the neural and genetic regulation of the critical vertebrate startle response circuitry through genetic, behavioral, cell labeling, and electrophysiological approaches in zebrafish. My three specific alms are to: 1) Identify and characterize the spaced out gene, thereby identifying a genetic regulator of the vertebrate neural circuitry controlling the startle response. These experiments will reveal the temporal and spatial requirements for this critical gene during neural development and function. 2) Determine the role of the spaced out gene in startle behavior modulation, revealing the both the range and specificity of this gene's roles in regulating neuronal populations which coordinate and modulate specific motor patterns in a variety of scenarios. These experiments will test the degree of overlap in vertebrate neural circuitry regulating distinct motor behaviors. 3) Characterize the neurons modulating startle behavior that are regulated by spaced out, detailing the neural activities and patterns of synaptic connections between neural components of startle circuitry. These experiments will reveal requirements for spaced out in both the development of crucial synaptic connections and in the activity of critical neurons during startle reflexes. Completing these aims will clarify the genetic basis for the neural modulation of vertebrate startle reflex movements. PUBLIC HEALTH RELEVANCE: The startle response is a rapid, whole-body reaction to a sudden potentially threatening stimulus serving to protect individuals from a dangerous situation. My work will reveal the genetic basis for how the nervous system controls this protective behavior, and more generally how the nervous system controls coordinated movement. Understanding how these circuits work and are controlled will lead to a clearer treatment path for neurological disorders or severe nerve injuries resulting in loss of coordination.