Präsynaptische HCN-Kanäle im Hippokampus: Regulation des axonalen Transports und synaptische Metaplastizität

海马突触前 HCN 通道：轴突运输和突触化塑性的调节

• 批准号: 103403401
• 负责人: Professor Dr. Roland A. Bender
• 金额: --
• 依托单位: Oscar Langendorff Institut für Physiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/103403401?language=en
• 关键词: Pr; synaptische; HCN; Kan; le

Synapses formed between perforant path axons and dentate gyrus granule cells constitute the first synapses in a neuronal loop connecting entorhinal cortex and hippocampus. They are important for memory formation and therefore endowed with a variety of mechanisms for synaptic plasticity. As the applicants have recently shown, these mechanisms include an age-dependent presynaptic expression of HCN1 channels. During the first funding period, their contribution to synaptic plasticity was examined in detail, and it was found that they affect LTP as well as LTD age-dependently. It was further found that regulation of the age-dependent axonal transport of HCN1 in perforant path involves the differential expression of isoforms of TRIP8b, a Rab8b-associated protein. For the second funding period, we propose experiments designed to deepen our understanding of these mechanisms. Questions addressed include: 1) How is the expression of TRIP8b isoforms in perforant path regulated? 2) What roles play posttranslational modifications identified for HCN1, such as ubiquitination or interaction with the sorting nexin SNX3, for the subcellular trafficking of the channels? 3) Does HCN1 functionally interact with other plasticity-related presynaptic proteins in perforant path, such as mGluRs or Cav3.2 channels? We believe that answering these questions will substantially further our knowledge of HCN1 regulation, and thus of synaptic plasticity, in the perforant path.

穿孔路径轴突和齿状回颗粒细胞之间形成的突触构成连接内嗅皮层和海马的神经元环中的第一个突触。它们对于记忆形成很重要，因此具有多种突触可塑性的机制。正如申请人最近所表明的那样，这些机制包括HCN1通道的年龄依赖性突触前表达。在第一个资金期间，详细研究了它们对突触可塑性的贡献，发现它们影响了LTP以及LTD年龄依赖性。进一步发现，穿孔路径中HCN1年龄依赖性轴突转运的调节涉及Trip8b的同工型的差异表达，Trip8b（一种Rab8b相关蛋白）。在第二个融资期间，我们提出了旨在加深对这些机制的理解的实验。解决的问题包括：1）在穿孔路径中，Trip8b同工型的表达如何受到调节？ 2）哪些角色扮演了针对HCN1确定的翻译后修饰，例如泛素化或与分类Nexin SNX3的相互作用，用于通道的亚细胞运输？ 3）HCN1是否会在诸如MGLURS或CAV3.2通道等穿孔路径中与其他与塑性相关的前突触前蛋白相互作用？我们认为，在穿孔道路上回答这些问题将大大进一步提高我们对HCN1调节的知识，因此将进一步了解突触可塑性。

项目成果

HCN1 subunits contribute to the kinetics of Ih in neonatal cortical plate neurons

• DOI: 10.1002/dneu.22104
• 发表时间: 2013-10
• 期刊: Developmental Neurobiology
• 影响因子: 3
• 作者: L. Stoenica;Wiebke Wilkars;Arne Battefeld;Konstantin Stadler;R. Bender;U. Strauss