Glutamate in Development of Auditory Brainstem

谷氨酸在听觉脑干发育中的作用

• 批准号: 6927535
• 负责人: DEDA C GILLESPIE
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927535
• 关键词: AMPA receptors; NMDA receptors; auditory nuclei; auditory pathways; developmental neurobiology; gamma aminobutyrate; gene expression; glutamate transporter; glycine; immunocytochemistry; laboratory rat; neural plasticity; neurotransmitter transport; olivary body; receptor expression; sound perception

DESCRIPTION (provided by applicant): The lateral superior olive (LSO), a binaural nucleus involved in sound localization, receives converging excitatory and inhibitory projections that are precisely tonotopically matched. The inhibitory projection from the MNTB is refined early in postnatal life through mechanisms that are largely unknown. It was recently found that inhibitory neurons in the MNTB-LSO projection release glutamate during the period of synaptic refinement. The vesicular glutamate transporter VGLUT3, which could support this glutamate release, is transiently expressed in the LSO during the same period and is downregulated shortly after hearing onset. This project will test the hypothesis that VGLUT3 expression in the LSO is downregulated by specific auditory experience. It also aims to test the hypothesis that different vesicular glutamate transporters specifically label the excitatory and inhibitory projections during development. The early glutamatergic transmission in the MNTB-LSO pathway is mediated in large part by postsynaptic NMDA receptors. NMDA receptors have known roles in synaptic plasticity in many systems, with different NMDA receptor subtypes playing distinct roles. Thus, an understanding of the particular NMDA receptor subtypes involved, and whether glutamate is likely to be co-released with GABA and glycine, will be necessary for further studies of glutamate's role in development of the LSO. The third arm of this proposal is to characterize basic physiology of glutamate transmission in both excitatory and inhibitory pathways, as a framework for further studies on the coordinated development of inhibitory and excitatory synapses. Conclusions from these studies will provide insight into the development of a major auditory nucleus, and may ramify beyond the auditory system to shed light on brain disorders involving abnormal inhibition, such as epilepsy and autism.

描述（由申请人提供）：与声音定位有关的双耳核的侧向上橄榄（LSO）接收到融合的兴奋性和抑制性投影，这些投影恰好是匹配的。 MNTB的抑制性投射在产后生活的早期通过在很大程度上未知的机制进行了完善。最近发现，在突触细化期间，MNTB-LSO投射释放谷氨酸盐中的抑制性神经元。可以支持该谷氨酸释放的囊泡谷氨酸转运蛋白vglut3在同一时期在LSO中暂时表达，并在听到发作后不久被下调。该项目将检验以下假设：LSO中的VGLUT3表达被特定的听觉经验下调。它还旨在检验以下假设：不同囊泡谷氨酸转运蛋白在发育过程中特异性标记兴奋性和抑制性投影。 MNTB-LSO途径中的早期谷氨酸能传播在突触后NMDA受体大部分介导。 NMDA受体在许多系统中都知道突触可塑性中的作用，其NMDA受体亚型发挥了不同的作用。因此，对涉及特定NMDA受体亚型的理解以及是否可能与GABA和甘氨酸共同发行谷氨酸，对于进一步研究谷氨酸在LSO开发中的作用是必要的。该提案的第三个部门是表征兴奋性和抑制途径中谷氨酸传播的基本生理学，作为对抑制性和兴奋性突触协调发展的进一步研究的框架。这些研究的结论将为主要听觉核的发展提供深入的了解，并可能使听觉系统超出听觉系统，以阐明涉及异常抑制的脑疾病，例如癫痫和自闭症。