Determining the structure-function variability of a mammalian neuronal circuit

Structure and function of brain circuits are tightly related by intrinsic and activity-dependent mechanisms, yet subject to stochastic events that may provide variability across individuals. Yet a fundamental question of neuroscience, identifying variability of mammalian neural circuits has so far been elusive. Synchrotron X-ray holotomography (XNH) is unique in reliably resolving non-destructively and densely neuronal processes in tissue, across volumes containing full neuronal circuits. Combining XNH with in vivo imaging, we address this question in a genetically targeted neuronal circuit. We aim to obtain a third biological replicate of the same circuit previously imaged at ID16A, answering the fundamental question of circuit variability and providing unique structure-function datasets of highest interest for wider neuroscience. Moreover, we will perform subsequent electron microscopy (EM) on imaged samples, for the first time combining in vivo imaging, X-ray tomography and EM.脑环路的结构与功能通过内在机制与活动依赖机制紧密耦合，但同时也会受到随机事件的影响，进而产生个体间的变异性。鉴定哺乳动物神经环路的变异性，是神经科学领域的核心基础问题，迄今为止仍未实现有效突破。同步辐射X射线全息断层成像（Synchrotron X-ray holotomography, XNH）具备独特优势，可在包含完整神经环路的三维组织体积内，以非破坏性方式可靠解析密集分布的神经元突起。本研究将XNH与活体成像技术相结合，在经遗传靶向标记的神经元环路中开展相关探究。我们计划获取此前在ID16A光束线中成像的同一环路的第三份生物学重复样本，以期解答神经环路变异性这一核心问题，并提供兼具独特性与高研究价值的结构-功能数据集，供更广范围的神经科学研究使用。此外，我们还将对已成像的样本开展后续电子显微镜（EM）检测，首次实现活体成像、X射线断层成像与电子显微镜技术的联用。