Mizuta Kotaro, Sato Masaaki
RIKEN BDR, Kobe, Japan.
New York University Abu Dhabi, Department of Biology, Abu Dhabi, United Arab Emirates.
Neurophotonics. 2024 Jul;11(3):033406. doi: 10.1117/1.NPh.11.3.033406. Epub 2024 Mar 8.
The function of the hippocampus in behavior and cognition has long been studied primarily through electrophysiological recordings from freely moving rodents. However, the application of optical recording methods, particularly multiphoton fluorescence microscopy, in the last decade or two has dramatically advanced our understanding of hippocampal function. This article provides a comprehensive overview of techniques and biological findings obtained from multiphoton imaging of hippocampal neural circuits.
This review aims to summarize and discuss the recent technical advances in multiphoton imaging of hippocampal neural circuits and the accumulated biological knowledge gained through this technology.
First, we provide a brief overview of various techniques of multiphoton imaging of the hippocampus and discuss its advantages, drawbacks, and associated key innovations and practices. Then, we review a large body of findings obtained through multiphoton imaging by region (CA1 and dentate gyrus), cell type (pyramidal neurons, inhibitory interneurons, and glial cells), and cellular compartment (dendrite and axon).
Multiphoton imaging of the hippocampus is primarily performed under head-fixed conditions and can reveal detailed mechanisms of circuit operation owing to its high spatial resolution and specificity. As the hippocampus lies deep below the cortex, its imaging requires elaborate methods. These include imaging cannula implantation, microendoscopy, and the use of long-wavelength light sources. Although many studies have focused on the dorsal CA1 pyramidal cells, studies of other local and inter-areal circuitry elements have also helped provide a more comprehensive picture of the information processing performed by the hippocampal circuits. Imaging of circuit function in mouse models of Alzheimer's disease and other brain disorders such as autism spectrum disorder has also contributed greatly to our understanding of their pathophysiology.
Multiphoton imaging has revealed much regarding region-, cell-type-, and pathway-specific mechanisms in hippocampal function and dysfunction in health and disease. Future technological advances will allow further illustration of the operating principle of the hippocampal circuits via the large-scale, high-resolution, multimodal, and minimally invasive imaging.
长期以来，主要通过对自由活动啮齿动物进行电生理记录来研究海马体在行为和认知中的功能。然而，在过去一二十年中，光学记录方法，特别是多光子荧光显微镜的应用，极大地推进了我们对海马体功能的理解。本文全面概述了从海马体神经回路的多光子成像中获得的技术和生物学发现。
本综述旨在总结和讨论海马体神经回路多光子成像的最新技术进展以及通过该技术积累的生物学知识。
首先，我们简要概述海马体多光子成像的各种技术，并讨论其优点、缺点以及相关的关键创新和实践。然后，我们按区域（CA1和齿状回）、细胞类型（锥体神经元、抑制性中间神经元和神经胶质细胞）以及细胞区室（树突和轴突）回顾通过多光子成像获得的大量研究结果。
海马体的多光子成像主要在头部固定的条件下进行，由于其高空间分辨率和特异性，能够揭示神经回路运作的详细机制。由于海马体位于皮层下方深处，其成像需要精细的方法。这些方法包括成像套管植入、显微内窥镜检查以及使用长波长光源。尽管许多研究集中在背侧CA1锥体细胞上，但对其他局部和区域间神经回路元件的研究也有助于更全面地了解海马体神经回路所执行的信息处理过程。对阿尔茨海默病和其他脑部疾病（如自闭症谱系障碍）小鼠模型中的神经回路功能成像，也极大地促进了我们对其病理生理学的理解。
多光子成像揭示了许多关于健康和疾病状态下海马体功能及功能障碍中区域、细胞类型和通路特异性机制的信息。未来的技术进步将通过大规模、高分辨率、多模态和微创成像进一步阐明海马体神经回路的运作原理。
