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

斑马鱼间隔基因在调节惊吓行为中的作用

• 批准号: 7806151
• 负责人: Roshan A Jain
• 金额: $ 5.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7806151
• 关键词: Acoustics; Behavior; Behavioral; Behavioral Genetics; Bilateral; Candidate Disease Gene; Cells; Chromosomes, Human, Pair 5; Code; Complement; Complex; Data; Defect; Dependence; Development; Drug Addiction; Ectopic Expression; Elements; Exhibits; Failure; Fiber; Functional Imaging; Genes; Genetic; Genetic Recombination; Genetic Screening; Head; Impaired cognition; In Situ Hybridization; Individual; Injection of therapeutic agent; Label; Larva; Lead; Left; Lesion; Maintenance; Maps; Mauthner' s neuron; Modality; Modification; Morphology; Motivation; Motor; Movement; Mutation; Nervous system structure; Neurons; Pattern; Performance; Population; Reaction; Reflex action; Regulation; Response Latencies; Role; Sensory; Site; Specificity; Speed; Staging; Stereotyping; Stimulus; Swimming; Synapses; System; Tail; Testing; Time; Touch sensation; Tracer; Vertebrates; Video Recording; Visual; Work; Zebrafish; base; hindbrain; in vivo; information processing; insight; interest; mutant; nerve injury; nervous system disorder; neural circuit; neurodevelopment; neuromechanism; neurophysiology; neuroregulation; overexpression; protective behavior; public health relevance; relating to nervous system; research study; response; sensory stimulus; spatiotemporal

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.

描述（由申请人提供）：像大多数运动行为一样，惊吓反射可以根据环境条件进行运动调节。尽管这种调节在多种神经系统疾病中受到干扰，但脊椎动物中这些破坏的遗传基础仍然知之甚少。我将重点关注从遗传筛选中分离出的运动缺陷的基因（间隔），这是惊吓反射调制所需的。当该基因被破坏时，个体会发起夸张且不当协调的反应。我将通过斑马鱼中的遗传，行为，细胞标记和电生理方法来揭示关键脊椎动物惊吓反应回路的神经和遗传调节。我的三个特定施舍是：1）识别和表征间隔的基因，从而确定控制惊吓反应的脊椎动物神经回路的遗传调节剂。这些实验将揭示该关键基因在神经发育和功能期间的时间和空间要求。 2）确定间隔基因在惊吓行为调制中的作用，揭示了该基因在调节神经元种群中的作用的范围和特异性，这些神经元种群在各种情况下协调和调节特定运动模式。这些实验将测试调节不同运动行为的脊椎动物神经回路的重叠程度。 3）表征由间隔分开调节的神经元调节惊吓行为，详细介绍了惊吓电路神经成分之间突触连接的神经活动和模式。这些实验将揭示在关键的突触连接发展和惊吓反射期间关键神经元活动中间隔的要求。 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。 公共卫生相关性：惊吓反应是对突然威胁刺激的迅速，全身反应，以保护个人免受危险情况。我的工作将揭示神经系统如何控制这种保护行为的遗传基础，更普遍地说神经系统如何控制协调的运动。了解这些电路的工作方式和控制方式将导致神经系统疾病或严重神经损伤的更清晰的治疗路径，从而导致协调丧失。