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MotAct-CSF - Characterization of CSF-contacting neurons physiological rolein the mammalian nervous system

MotAct-CSF - 哺乳动物神经系统中 CSF 接触神经元生理作用的表征

基本信息

批准号：
316642629
负责人：
Dr. Niccolo Zampieri, Ph.D.
金额：
--
依托单位：
Forschungsschwerpunkt Erkrankungen des Nervensystems
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2016
资助国家：
德国
起止时间：
2015-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/316642629?language=en
关键词：
MotAct CSF Characterization contacting neurons

项目摘要

This proposal aims at elucidating the physiological, molecular and anatomical properties of cerebrospinal fluid-contacting neurons (CSF-cNs) in the mammalian central nervous system. CSF-cNs are a unique neuronal population, conserved from lower vertebrates to primates, lining the central canal (CC) at all medullospinal levels and are characterized by selective expression of the Polycystin Kidney Disease 2-Like 1 channel (PKD2L1) These neurons are highly polarized cells with a dendrite projecting to the CC and forming a large protrusion in contact with the CSF, while their axons appear to extend in the parenchyma along the longitudinal axis of the ventral spinal cord. CSF-cNs are strategically positioned to monitor CSF composition and sense mechanical deformation of the spine, thus possible functions in providing sensory information about the physiological and/or postural state of the organism have been hypothesized.In recent studies, we conducted pioneering characterization of the physiology and anatomy of mouse medullar CSF-cNs, demonstrating expression of functional ionotropic receptors and spontaneous PKD2L1 channel activity capable of regulating CSF-cNs excitability. We also described that CSF-cNs positioning around the CC varies at different segmental levels, suggesting potential differences in physiological properties, circuitry and function along the rostro-caudal axis of CNS. However, to date, the role of CSF-cNs in the central nervous system remains unknown.By combining electrophysiological, calcium imaging, molecular and viral tracing techniques, we propose to determine for the first time in mammals the molecular profile, cellular and connectivity properties of CSF-cNs at different medullospinal levels according to the following specific aims:AIM 1 - Physiology and synaptic integration of CSF-cNs A. CSF-cNs electrophysiological properties and calcium homeostasisB. Region specific transcriptomic on isolated medullospinal CSF-cNsC. Identification of CSF-cNs input/output relationships and modulation of their activityAIM 2 - Characterization of CSF-cNs input-output connectivityA. Identification of CSF-cNs projection patterns and pre-synaptic terminalsB. Mapping CSF-cNs circuitsC. Identification of CSF-cNs pre- and post-synaptic partnersThe proposed studies will advance our current understanding of CSF-cNs biology to fully characterize their molecular and cellular properties at different levels of the medullospinal system. Moreover, we will determine both anatomically and functionally the specific neuronal networks CSF-cNs are inserted in. Altogether, these data will be a necessary step to define the function of CSF-cNs in the mammalian central nervous system.

本研究旨在阐明哺乳动物中枢神经系统接触脑脊液神经元（CSF-cNs）的生理、分子和解剖学特性。CSF-cN是一种独特的神经元群体，从低等脊椎动物到灵长类动物都是保守的，在所有脊髓水平上排列在中央管（CC）上，并且特征在于选择性表达多囊蛋白肾病2样1通道（PKD 2L 1）。这些神经元是高度极化的细胞，具有突起到CC的树突并形成与CSF接触的大突起，而它们的轴突似乎在实质中沿着腹侧脊髓的纵轴沿着延伸。CSF-cNs被战略性地定位以监测CSF组成和感测脊柱的机械变形，因此在提供关于生物体的生理和/或姿势状态的感觉信息中的可能功能已经被假设。证明了功能性离子型受体的表达和能够调节CSF-cNs兴奋性的自发PKD 2L 1通道活性。我们还描述了CSF-cNs在CC周围的定位在不同节段水平上不同，这表明CNS的沿着喙尾轴的生理特性、回路和功能存在潜在差异。然而，迄今为止，CSF-cNs在中枢神经系统中的作用仍然未知，通过结合电生理学、钙成像、分子和病毒示踪技术，我们首次提出在哺乳动物中确定CSF-cNs在不同脊髓水平的分子概况、细胞和连接特性，具体目标如下：目的1 -CSF-cNs的生理和突触整合A. CSF-cNs的电生理特性和钙稳态B.分离的脊髓CSF-cNsC的区域特异性转录组学。CSF-cNs输入/输出关系的鉴定及其活性的调节AIM 2 -CSF-cNs输入-输出连接性的表征CSF-cNs投射模式和突触前终末的鉴定映射CSF-cNs电路CSF-cNs突触前和突触后伴侣的鉴定这些研究将促进我们目前对CSF-cNs生物学的理解，以充分表征其在脊髓系统不同水平的分子和细胞特性。此外，我们将在解剖学和功能上确定CSF-cNs插入的特定神经元网络。总之，这些数据将是一个必要的步骤，以确定在哺乳动物中枢神经系统的CSF-cNs的功能。