Development of Inhibition in the Avian Cochlear Nucleus

禽耳蜗核抑制的发展

• 批准号: 7113269
• 负责人: MacKenzie A Howard
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-09 至 2009-07-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113269
• 关键词: GABA receptor; RNA interference; afferent nerve; auditory nuclei; auditory pathways; chick embryo; cochlear nerve; developmental neurobiology; electrical conductance; electrophysiology; electroporation; gamma aminobutyrate; genetic regulation; green fluorescent proteins; ion channel blocker; neural inhibition; neurogenesis; neurons; neurophysiology; nonmammalian vertebrate embryology; otocyst /otolith; phenotype; predoctoral investigator; sectioning; synapses; time perception; voltage /patch clamp

DESCRIPTION (provided by applicant): The auditory system localizes sound in azimuth by computing interaural time delays. In the avian auditory brainstem, nucleus magnocellularis (NM) is the first central nucleus in this temporal coding pathway. NM contains highly specialized anatomic, synaptic, and intrinsic properties that play key roles in shaping inhibitory responses and maintaining temporal fidelity in NM. The development of these specializations is poorly understood. The first aim is to describe the time-course of the development of inhibition in chick NM using in vitro electrophysiological techniques.. The second aim is to understand the developmental importance of afferent excitatory inputs in the development of inhibition using otocyst removal followed by physiological recordings. The third aim will examine role of Kv1.1 in developing the normal NM phenotype using RNA interference techniques. Plasmids encoding RNAs designed to interfere with the Kcnal, the Kv1.1 gene, and an EGFP reporter gene will be electroporated in ovo in early embryos. The physiology of transfected cells will be examined through development. These manipulations are hypothesized to alter the normal development of NM anatomy and physiological responses to excitatory and inhibitory inputs.

描述(申请人提供)：听觉系统通过计算耳间时间延迟在方位上定位声音。在鸟类听性脑干中，巨细胞核(NM)是这一时间编码通路的第一个中央核。NM包含高度专门化的解剖、突触和固有特性，这些特性在形成抑制反应和维持NM的时间保真度方面发挥关键作用。人们对这些专业的发展知之甚少。第一个目的是用体外电生理技术描述雏鸡NM抑制发展的时程。第二个目的是通过耳囊摘除和生理记录来了解传入兴奋性输入在抑制发展中的重要性。第三个目的是利用RNA干扰技术检测Kv1.1在正常NM表型形成中的作用。编码干扰Kcnal、Kv1.1基因和EGFP报告基因的RNAs的质粒将在早期胚胎的卵子中进行电穿孔。转基因细胞的生理学将通过培养进行检测。这些操作被认为是为了改变NM解剖的正常发展和对兴奋性和抑制性输入的生理反应。