Visualization and molecular characterization of whole-brain vascular networks with capillary resolution

Miyawaki, Takeyuki; Morikawa, Shota; Susaki, Etsuo A.; Nakashima, Ai; Takeuchi, Haruki; Yamaguchi, Shun; Ueda, Hiroki R.; Ikegaya, Yuji

doi:10.1038/s41467-020-14786-z

Cited by 64 publications

(40 citation statements)

References 40 publications

(50 reference statements)

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“…In addition, for successful whole-cell recording, the tips of the patch pipettes must be kept as clean as possible to form a high-resistance seal on the cell membrane [ 82 ]. When researchers attempt to record membrane potentials from deep regions in vivo, some “obstacles” such as the extracellular matrix [ 83 ] and blood vessels [ 84 , 85 ] are more likely to adhere to the pipette tip. The dirty tips prevent a giga-ohm seal, causing a low success rate for whole-cell recording from the deep region of anesthetized and awake animals.…”

Section: In Vivo Whole-cell Recordings From Awake Animalsmentioning

confidence: 99%

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

Noguchi

Ikegaya

Matsumoto

2021

Sensors

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Brain functions are fundamental for the survival of organisms, and they are supported by neural circuits consisting of a variety of neurons. To investigate the function of neurons at the single-cell level, researchers often use whole-cell patch-clamp recording techniques. These techniques enable us to record membrane potentials (including action potentials) of individual neurons of not only anesthetized but also actively behaving animals. This whole-cell recording method enables us to reveal how neuronal activities support brain function at the single-cell level. In this review, we introduce previous studies using in vivo patch-clamp recording techniques and recent findings primarily regarding neuronal activities in the hippocampus for behavioral function. We further discuss how we can bridge the gap between electrophysiology and biochemistry.

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Section: In Vivo Whole-cell Recordings From Awake Animalsmentioning

confidence: 99%

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

Noguchi

Ikegaya

Matsumoto

2021

Sensors

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“…The method combines a thermally controlled vessel casting method with a bile salt-based tissue clearing technique to optimize the function of observing cranial blood vessels. Compared with the classic vascular casting or lectin transcardial perfusion method, SeeNet shows close to 100% vascular coverage, thus becoming a promising tool to reveal unknown vascular access and complete the cerebrovascular network's connectivity 58 . The “skull optical clearance window” presents a novel strategy to image cerebral blood vessels of mice in vivo.…”

Section: Visualizing Morphological Details Of Blood Vessels In the Brmentioning

confidence: 99%

Optical Tissue Clearing: Illuminating Brain Function and Dysfunction

Liang¹,

Luo²

2021

Theranostics

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Tissue optical clearing technology has been developing rapidly in the past decade due to advances in microscopy equipment and various labeling techniques. Consistent modification of primary methods for optical tissue transparency has allowed observation of the whole mouse body at single-cell resolution or thick tissue slices at the nanoscale level, with the final aim to make intact primate and human brains or thick human brain tissues optically transparent. Optical clearance combined with flexible large-volume tissue labeling technology can not only preserve the anatomical structure but also visualize multiple molecular information from intact samples in situ. It also provides a new strategy for studying complex tissues, which is of great significance for deciphering the functional structure of healthy brains and the mechanisms of neurological pathologies. In this review, we briefly introduce the existing optical clearing technology and discuss its application in deciphering connection and structure, brain development, and brain diseases. Besides, we discuss the standard computational analysis tools for large-scale imaging dataset processing and information extraction. In general, we hope that this review will provide a valuable reference for researchers who intend to use optical clearing technology in studying the brain.

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“…Currently, the lymphatic system in the mouse and human brain were revealed [ 4 , 8 , 16 ]. The whole visualization of blood vessels by rendering brain tissue transparent [ 17 ] and a molecular atlas for the blood vascular and vessel-associated cells in mouse brains using vascular single-cell transcriptomics [ 18 ] are also available, and they are extremely helpful to expand our knowledge. Therefore, a lot of attention is paid to the fact that brain inflammation, lymphedema, aberrant immunity, hypertension, and obesity result in various alterations in the vascular and lymphatic systems, such as leakage, damage, cleavage, hypo- and hyper-plasia [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Segawa

Blumenthal

Yamawaki

et al. 2021

Biology

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The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

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Visualization and molecular characterization of whole-brain vascular networks with capillary resolution

Cited by 64 publications

References 40 publications

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

In Vivo Whole-Cell Patch-Clamp Methods: Recent Technical Progress and Future Perspectives

Optical Tissue Clearing: Illuminating Brain Function and Dysfunction

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

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