SCREENING MICE FOR AUDITORY & NEUROBEHAVIORAL PHENOTYPES

筛查小鼠的听觉

• 批准号: 6403266
• 负责人: JAMES F WILLOTT
• 金额: $ 17.4万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6403266
• 关键词: Mus musculus; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; computer program /software; computer system design /evaluation; computer system hardware; diagnosis design /evaluation; emotions; fear; genetic strain; hearing disorders; hearing tests; learning disorders; method development; neuropsychology; paired stimuli; phenotype; psychoacoustics; sensory disorder diagnosis; startle reaction

The overall goal is to develop, evaluate, and standardize a set of procedures that use acoustic startle response (ASR) modification to identify phenotypes for use in research on hearing impairments, certain neurobehavioral disorders, learning ability, and emotionality. Specific aims are to develop procedures and establish performance "norms" using common strains of mice. Basic properties of the ASR will be determined. Prepulse inhibition (PPI) will be used to identify possible hearing deficits. PPI is also a measure of "sensory gating," and is diminished in human patients with neurobehavioral disorders such as schizophrenia. If a mouse exhibits poor PPI but has good hearing (determined by a second-level screening test using the auditory brainstem response), the poor PPI would be taken as evidence for a deficit in sensory gating. PPI will be further evaluated as well, increasing the likelihood of detecting gating deficits. Habituation of the ASR will be assessed also, because this is abnormal in schizophrenia and anxiety disorders. The fear-potentiated startle (FPS) and freezing paradigms will be used to assess learning ability and emotionality. Both can be evaluated in the same screening protocol. Poor performance on either task would suggest an emotional learning deficit. Stimulus and testing paradigms will be refined and optimized in conjunction with the testing of the common strains of mice. Performance means and variances will be established for each strain, providing criteria for testing of existing mutants. The startle and PPI paradigms will be developed by Dr. Willott at Northern Illinois University; the FPS and freezing by Dr. Falls at the University of Vermont. Ultimately, the methods will be integrated, refined, and tested on existing neurological and other mutant mice at the Jackson Laboratory under the supervision of Dr. Johnson. This will be accompanied by development of an easy-to-use software/ hardware package that will integrate all screening techniques in a single, serial protocol for use on individual mice.

总体目标是开发、评估和标准化一套程序，使用声惊吓反应 (ASR) 修饰来识别表型，用于听力障碍、某些神经行为障碍、学习能力和情绪的研究。 具体目标是使用常见品系的小鼠开发程序并建立性能“规范”。 ASR 的基本属性将被确定。前脉冲抑制（PPI）将用于识别可能的听力缺陷。 PPI 也是“感觉门控”的一种测量方法，在患有精神分裂症等神经行为障碍的人类患者中，PPI 会减弱。 如果小鼠的 PPI 较差，但听力良好（通过使用听觉脑干反应的二级筛选测试确定），则较差的 PPI 将被视为感觉门控缺陷的证据。 PPI 也将得到进一步评估，增加检测门控缺陷的可能性。 还将评估 ASR 的习惯，因为这在精神分裂症和焦虑症中是异常的。 恐惧增强惊吓（FPS）和冻结范式将用于评估学习能力和情绪。 两者都可以在同一筛选方案中进行评估。 任何一项任务的表现不佳都表明情绪学习缺陷。刺激和测试范例将结合常见小鼠品系的测试进行细化和优化。将为每个菌株建立性能平均值和方差，为现有突变体的测试提供标准。 startle 和 PPI 范式将由北伊利诺伊大学的 Willott 博士开发；佛蒙特大学 Falls 博士的 FPS 和冷冻。 最终，这些方法将在约翰逊博士的监督下，在杰克逊实验室的现有神经小鼠和其他突变小鼠上进行整合、完善和测试。 这将伴随着易于使用的软件/硬件包的开发，该包将所有筛选技术集成在单个串行协议中，以用于单个小鼠。