Functional biochemical compartmentilization in aspiny neurons

神经细胞通过被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都是在高度特化的细胞结构上形成的，这些细胞结构被称为树突棘。人们普遍认为，每根脊椎至少形成一个突触，并代表一个独立于邻近突触运作的独特的生化室。令人惊讶的是，大脑中大约三分之一的神经元没有脊髓，直接接受树突轴上的兴奋性传入信号。虽然这种情况下的信号转导假定单个突触之间存在一定程度的串扰，但这并没有发生，而且突触通信仍然局限于激活的突触，而不影响相邻的突触。这就提出了一个重要的问题：即，刺突神经元是如何完成弥漫性分离和突触特异性信号转导的？我们认为，不同传入事件形成的突触具有特定的突触后功能生化区隔机制，产生具有特定性质和不同生理作用的信号微域。为了确定棘突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篮状细胞两种兴奋性突触的突触后Ca2+信号：由Schaffer侧枝和穿孔通路支配的突触。结合双光子显微镜、电生理学、药理学和分子技术，将评估不同突触内突触后Ca2+信号的时空分布及其调控和生理意义。

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.