Functional biochemical compartmentilization in aspiny neurons

无刺神经元的功能生化区室化

• 批准号: 342292-2007
• 负责人: Topolnik, LisaYelyzaveta
• 金额: $ 2.84万
• 依托单位: Université Laval
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2011
• 资助国家: 加拿大
• 起止时间: 2011-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=482464
• 关键词: Functional; biochemical; compartmentilization; aspiny; neurons

Nerve cells are connected to each other by tiny contacts, called synapses. The majority of excitatory synapses in the brain are formed onto highly specialized cellular structures known as dendritic spines. It is generally accepted that every spine forms at least one synapse and represents a distinct biochemical compartment operating independently from neighboring synapses. Surprisingly, about one third of neurons in the brain lack spines and receive excitatory afferents directly onto the dendritic shaft. While signal transduction in this case presumes a certain degree of cross talk among individual synapses, this does not happen and synaptic communication in aspiny neurons remains confined to activated synapses without affecting neighboring ones. This raises an important question: that is, how may aspiny neurons accomplish diffusionally isolated and synapse-specific signal transduction? We propose that synapses formed by different afferents possess specific postsynaptic mechanisms for functional biochemical compartmentalization, which produce signaling microdomains with specific properties and distinct physiological roles. To determine the synapse-specific mechanisms of postsynaptic calcium compartmentalization in aspiny neurons, we will examine postsynaptic Ca2+ signals at two types of excitatory synapses of hippocampal CA1 basket cells: synapses innervated by the Schaffer collaterals and the perforant path. A combination of two-photon microscopy, electrophysiology, pharmacology, and molecular techniques will be used to assess the spatio-temporal profile of postsynaptic Ca2+ signals within different synapses as well as their regulation and physiological significance.

神经细胞通过称为突触的微小接触相互连接。大脑中的大多数兴奋性突触形成于高度特化的细胞结构上，称为树突棘。人们普遍认为，每个棘形成至少一个突触，并代表独立于邻近突触运行的独特生化区室。令人惊讶的是，大脑中大约三分之一的神经元缺乏棘，直接在树突轴上接收兴奋性传入信号。虽然这种情况下的信号转导假定各个突触之间存在一定程度的串扰，但这并不会发生，无刺神经元中的突触通讯仍然局限于激活的突触，而不影响邻近的突触。这就提出了一个重要的问题：即无刺神经元如何实现扩散隔离和突触特异性的信号转导？我们提出，由不同传入神经形成的突触具有用于功能性生化区室化的特定突触后机制，其产生具有特定性质和不同生理作用的信号微域。为了确定无刺神经元突触后钙区室化的突触特异性机制，我们将检查海马 CA1 篮细胞两种兴奋性突触的突触后 Ca2+ 信号：由 Schaffer 侧支和穿通通路支配的突触。双光子显微镜、电生理学、药理学和分子技术的结合将用于评估不同突触内突触后 Ca2+ 信号的时空分布及其调节和生理意义。