Mechanisms of plasticity at the Mossy Fiber Synapse

苔藓纤维突触的可塑性机制

• 批准号: 7039076
• 负责人: Anis Contractor
• 金额: $ 29.72万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7039076
• 关键词: SDS polyacrylamide gel electrophoresis; actins; calcium flux; computer program /software; ephrins; gene mutation; genetically modified animals; immunocytochemistry; laboratory mouse; light microscopy; long term potentiation; mossy fiber; neural transmission; neuroanatomy; neurotransmitter receptor; neurotransmitter transport; polymerization; protein protein interaction; pyramidal cells; synapses

DESCRIPTION (provided by applicant): Activity driven modification of excitatory synapses is an exquisitely powerful process for the refinement of synaptic connections. Long-term potentiation (LTP) of synaptic transmission in the hippocampus is widely accepted to be integral to the formation and consolidation of memories. Due to the complexity and heterogeneity of the molecules underlying LTP, many of the cellular mechanisms are still not fully established. A complete description of these fundamental processes will allow us to understand the pathology of neurological disorders that result in the disruption of memory storage and retrieval. The mossy fiber synapse provides one of the main excitatory inputs to the CA3 region of the hippocampus. The recurrent network of the CA3 is particularly important in the storage and retrieval of associative memories. The mossy fiber synapse is critical to the modulation of this network and therefore is central to hippocampal function. Mossy fiber plasticity demonstrates some very interesting properties. LTP is expressed in the presynaptic terminal of the synapse, however there is still controversy over the site of induction. Recent findings have demonstrated a role for postsynaptic mechanism in the induction of mossy fiber LTP followed by trans-synaptic signaling to the pre-synapse, mediated by Eph receptor-ephrin interactions. In order to further explore the molecules involved in this unique pathway, this study will make use of mutant mice in which the relevant proteins have been genetically ablated or mutated to disrupt their signaling function. In addition, we will explore the exact pre- and postsynaptic mechanisms by which these molecules exert their action. These studies will provide new insight relevant to synaptic transmission and memory processes in the mammalian brain.

描述（由申请人提供）：兴奋性突触的活动驱动的修改是完善突触连接的精确过程。海马中突触传播的长期增强（LTP）被广泛接受为记忆的形成和巩固不可或缺的一部分。由于LTP的分子的复杂性和异质性，许多细胞机制仍未完全确定。对这些基本过程的完整描述将使我们能够理解导致记忆存储和检索中断的神经系统疾病的病理。苔藓纤维突触为海马的CA3区域提供了主要的兴奋性输入之一。 CA3的复发网络在存储和检索关联记忆中尤为重要。苔藓纤维突触对于该网络的调制至关重要，因此对于海马功能至关重要。苔藓纤维可塑性表现出一些非常有趣的特性。 LTP在突触的突触前末端表示，但是诱导部位仍然存在争议。最近的发现表明，突触后机制在诱导苔藓纤维LTP的诱导中起作用，然后通过EPH受体磷蛋白相互作用介导的跨性突触信号传导。为了进一步探索这一独特途径所涉及的分子，本研究将利用突变小鼠，其中相关蛋白已在遗传上消融或突变以破坏其信号传导功能。此外，我们将探索这些分子发挥作用的确切前后突触后机制。这些研究将为哺乳动物大脑中的突触传播和记忆过程提供新的见解。