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.

穿通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路中的第一个突触。它们对于记忆形成很重要，因此被赋予多种突触可塑性机制。正如申请人最近所表明的，这些机制包括 HCN1 通道的年龄依赖性突触前表达。在第一个资助期间，详细检查了它们对突触可塑性的贡献，发现它们对 LTP 和 LTD 的影响与年龄相关。进一步发现，穿通路径中 HCN1 年龄依赖性轴突运输的调节涉及 Rab8b 相关蛋白 TRIP8b 亚型的差异表达。对于第二个资助期，我们提出了旨在加深我们对这些机制的理解的实验。解决的问题包括：1) TRIP8b 同工型在穿通路径中的表达是如何调节的？ 2) HCN1 的翻译后修饰（例如泛素化或与分选连接蛋白 SNX3 相互作用）在通道的亚细胞运输中发挥什么作用？ 3) HCN1 是否与穿通路径中其他可塑性相关的突触前蛋白（例如 mGluR 或 Cav3.2 通道）发生功能性相互作用？我们相信，回答这些问题将大大加深我们对 HCN1 调节的了解，从而进一步了解穿通路径中的突触可塑性。

项目成果

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

HCN1 亚基有助于新生儿皮质板神经元的 Ih 动力学

• DOI: 10.1002/dneu.22104
• 发表时间: 2013-10-01
• 期刊: Developmental Neurobiology
• 影响因子: 3
• 作者: L. Stoenica;Wiebke Wilkars;Arne Battefeld;Konstantin Stadler;R. Bender;U. Strauss
• 通讯作者: U. Strauss

Nedd4‐2 regulates surface expression and may affect N‐glycosylation of hyperpolarization‐activated cyclic nucleotide‐gated (HCN)‐1 channels

• DOI: 10.1096/fj.13-242032
• 发表时间: 2014-05-01
• 期刊: The FASEB Journal
• 作者: Wiebke Wilkars;Jessica Wollberg;E. Mohr;M. Han;D. Chetkovich;R. Bähring;R. Bender
• 通讯作者: R. Bender