Current Techniques for Investigating the Brain Extracellular Space
The brain extracellular space (ECS) is a continuous reticular compartment that lies between the cells of the brain. It is vast in extent relative to its resident cells, yet, at the same time the nano- to micrometer dimensions of its channels and reservoirs are commonly finer than the smallest cellul...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.570750/full |
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| author | Federico N. Soria Federico N. Soria Cristina Miguelez Cristina Miguelez Olga Peñagarikano Jan Tønnesen Jan Tønnesen |
| author_facet | Federico N. Soria Federico N. Soria Cristina Miguelez Cristina Miguelez Olga Peñagarikano Jan Tønnesen Jan Tønnesen |
| author_sort | Federico N. Soria |
| collection | DOAJ |
| description | The brain extracellular space (ECS) is a continuous reticular compartment that lies between the cells of the brain. It is vast in extent relative to its resident cells, yet, at the same time the nano- to micrometer dimensions of its channels and reservoirs are commonly finer than the smallest cellular structures. Our conventional view of this compartment as largely static and of secondary importance for brain function is rapidly changing, and its active dynamic roles in signaling and metabolite clearance have come to the fore. It is further emerging that ECS microarchitecture is highly heterogeneous and dynamic and that ECS geometry and diffusional properties directly modulate local diffusional transport, down to the nanoscale around individual synapses. The ECS can therefore be considered an extremely complex and diverse compartment, where numerous physiological events are unfolding in parallel on spatial and temporal scales that span orders of magnitude, from milliseconds to hours, and from nanometers to centimeters. To further understand the physiological roles of the ECS and identify new ones, researchers can choose from a wide array of experimental techniques, which differ greatly in their applicability to a given sample and the type of data they produce. Here, we aim to provide a basic introduction to the available experimental techniques that have been applied to address the brain ECS, highlighting their main characteristics. We include current gold-standard techniques, as well as emerging cutting-edge modalities based on recent super-resolution microscopy. It is clear that each technique comes with unique strengths and limitations and that no single experimental method can unravel the unknown physiological roles of the brain ECS on its own. |
| first_indexed | 2024-12-13T03:09:43Z |
| format | Article |
| id | doaj.art-5a05e4fd392640c7b3ff97f0df829087 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T03:09:43Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-5a05e4fd392640c7b3ff97f0df8290872022-12-22T00:01:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-10-011410.3389/fnins.2020.570750570750Current Techniques for Investigating the Brain Extracellular SpaceFederico N. Soria0Federico N. Soria1Cristina Miguelez2Cristina Miguelez3Olga Peñagarikano4Jan Tønnesen5Jan Tønnesen6Achucarro Basque Center for Neuroscience, Leioa, SpainDepartment of Neuroscience, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainAutonomic and Movement Disorders Unit, Neurodegenerative Diseases, Biocruces Health Research Institute, Barakaldo, SpainDepartment of Pharmacology, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainAchucarro Basque Center for Neuroscience, Leioa, SpainDepartment of Neuroscience, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, SpainThe brain extracellular space (ECS) is a continuous reticular compartment that lies between the cells of the brain. It is vast in extent relative to its resident cells, yet, at the same time the nano- to micrometer dimensions of its channels and reservoirs are commonly finer than the smallest cellular structures. Our conventional view of this compartment as largely static and of secondary importance for brain function is rapidly changing, and its active dynamic roles in signaling and metabolite clearance have come to the fore. It is further emerging that ECS microarchitecture is highly heterogeneous and dynamic and that ECS geometry and diffusional properties directly modulate local diffusional transport, down to the nanoscale around individual synapses. The ECS can therefore be considered an extremely complex and diverse compartment, where numerous physiological events are unfolding in parallel on spatial and temporal scales that span orders of magnitude, from milliseconds to hours, and from nanometers to centimeters. To further understand the physiological roles of the ECS and identify new ones, researchers can choose from a wide array of experimental techniques, which differ greatly in their applicability to a given sample and the type of data they produce. Here, we aim to provide a basic introduction to the available experimental techniques that have been applied to address the brain ECS, highlighting their main characteristics. We include current gold-standard techniques, as well as emerging cutting-edge modalities based on recent super-resolution microscopy. It is clear that each technique comes with unique strengths and limitations and that no single experimental method can unravel the unknown physiological roles of the brain ECS on its own.https://www.frontiersin.org/article/10.3389/fnins.2020.570750/fullsingle particle trackingSTED microscopybrain parenchymaglymphatic systemsuper-resolutionreal-time iontophoresis |
| spellingShingle | Federico N. Soria Federico N. Soria Cristina Miguelez Cristina Miguelez Olga Peñagarikano Jan Tønnesen Jan Tønnesen Current Techniques for Investigating the Brain Extracellular Space Frontiers in Neuroscience single particle tracking STED microscopy brain parenchyma glymphatic system super-resolution real-time iontophoresis |
| title | Current Techniques for Investigating the Brain Extracellular Space |
| title_full | Current Techniques for Investigating the Brain Extracellular Space |
| title_fullStr | Current Techniques for Investigating the Brain Extracellular Space |
| title_full_unstemmed | Current Techniques for Investigating the Brain Extracellular Space |
| title_short | Current Techniques for Investigating the Brain Extracellular Space |
| title_sort | current techniques for investigating the brain extracellular space |
| topic | single particle tracking STED microscopy brain parenchyma glymphatic system super-resolution real-time iontophoresis |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.570750/full |
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