Three-dimensional synaptic organization of the human hippocampal CA1 field

The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method usin...

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Autores: Montero-Crespo, M., Domínguez-Álvaro, M., Rondon-Carrillo, P., Alonso-Nanclares, Lidia, DeFelipe, Javier, Blázquez-Llorca, Lidia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/229381
Acceso en línea:http://hdl.handle.net/10261/229381
Access Level:acceso abierto
Palabra clave:dementia, electron microscopy, FIB/SEM, hippocampus, synapses
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dc.title.none.fl_str_mv Three-dimensional synaptic organization of the human hippocampal CA1 field
title Three-dimensional synaptic organization of the human hippocampal CA1 field
spellingShingle Three-dimensional synaptic organization of the human hippocampal CA1 field
Montero-Crespo, M.
dementia, electron microscopy, FIB/SEM, hippocampus, synapses
title_short Three-dimensional synaptic organization of the human hippocampal CA1 field
title_full Three-dimensional synaptic organization of the human hippocampal CA1 field
title_fullStr Three-dimensional synaptic organization of the human hippocampal CA1 field
title_full_unstemmed Three-dimensional synaptic organization of the human hippocampal CA1 field
title_sort Three-dimensional synaptic organization of the human hippocampal CA1 field
dc.creator.none.fl_str_mv Montero-Crespo, M.
Domínguez-Álvaro, M.
Rondon-Carrillo, P.
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blázquez-Llorca, Lidia
author Montero-Crespo, M.
author_facet Montero-Crespo, M.
Domínguez-Álvaro, M.
Rondon-Carrillo, P.
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blázquez-Llorca, Lidia
author_role author
author2 Domínguez-Álvaro, M.
Rondon-Carrillo, P.
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blázquez-Llorca, Lidia
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Alzheimer's Association
Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)
Universidad Nacional de Educación a Distancia (España)
Ministerio de Educación, Cultura y Deporte (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv dementia, electron microscopy, FIB/SEM, hippocampus, synapses
topic dementia, electron microscopy, FIB/SEM, hippocampus, synapses
description The hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.There are billions of nerve cells or neurons in the human brain, and each one can form thousands of connections, also called synapses, with other neurons. That means there are trillions of synapses in the brain that keep information flowing. Studying the arrangement of individual neurons in the human brain, and the connections between them, is incredibly difficult because of its complexity. Scientists have tools that can image the whole brain and can measure the activity in different regions, but these tools only visualize brain structures that are large enough to be seen with human eyes. Synapses are much smaller (in the range of nanometers), and can only be seen using thin slices of preserved brain tissue through a technique called electron microscopy. The hippocampus is a part of the human brain that is critical for memory, learning and spatial orientation, and is affected in epilepsy and Alzheimer’s disease. Although numerous studies of the hippocampus have been performed in laboratory animals, such as mice, the question remains as to how much of the information gained from these studies applies to humans. Thus, studying the human brain directly is a major goal in neuroscience. However, the scarcity of human brain tissue suitable for the study of synapses is one of the most important issues to overcome. Fortunately, healthy human brain tissue that can be studied using electron microscopy is sometimes donated after death. Using these donations could improve the understanding of the synapses in normal brains and possible changes associated with disease. Now, Montero-Crespo et al. have mapped synapses in the normal human hippocampus in three dimensions – providing the first detailed description of synaptic structure in this part of the brain. Using high-powered electron microscopes and donated brain tissue samples collected after death, Montero-Crespo et al. imaged almost 25,000 connections between neurons. The analysis showed that synapses were more densely packed in some layers of the hippocampus than in others. Most synapses were found to be connected to tiny dendritic ‘spines’ that sprout from dendritic branches of the neuron, and they activated (not suppressed) the next neuron. Beyond its implications for better understanding of brain health and disease, this work could also advance computer modelling attempts to mimic the structure of the brain and its activity.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
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eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
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spelling Three-dimensional synaptic organization of the human hippocampal CA1 fieldMontero-Crespo, M.Domínguez-Álvaro, M.Rondon-Carrillo, P.Alonso-Nanclares, LidiaDeFelipe, JavierBlázquez-Llorca, Lidiadementia, electron microscopy, FIB/SEM, hippocampus, synapsesThe hippocampal CA1 field integrates a wide variety of subcortical and cortical inputs, but its synaptic organization in humans is still unknown due to the difficulties involved studying the human brain via electron microscope techniques. However, we have shown that the 3D reconstruction method using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM) can be applied to study in detail the synaptic organization of the human brain obtained from autopsies, yielding excellent results. Using this technology, 24,752 synapses were fully reconstructed in CA1, revealing that most of them were excitatory, targeting dendritic spines and displaying a macular shape, regardless of the layer examined. However, remarkable differences were observed between layers. These data constitute the first extensive description of the synaptic organization of the neuropil of the human CA1 region.There are billions of nerve cells or neurons in the human brain, and each one can form thousands of connections, also called synapses, with other neurons. That means there are trillions of synapses in the brain that keep information flowing. Studying the arrangement of individual neurons in the human brain, and the connections between them, is incredibly difficult because of its complexity. Scientists have tools that can image the whole brain and can measure the activity in different regions, but these tools only visualize brain structures that are large enough to be seen with human eyes. Synapses are much smaller (in the range of nanometers), and can only be seen using thin slices of preserved brain tissue through a technique called electron microscopy. The hippocampus is a part of the human brain that is critical for memory, learning and spatial orientation, and is affected in epilepsy and Alzheimer’s disease. Although numerous studies of the hippocampus have been performed in laboratory animals, such as mice, the question remains as to how much of the information gained from these studies applies to humans. Thus, studying the human brain directly is a major goal in neuroscience. However, the scarcity of human brain tissue suitable for the study of synapses is one of the most important issues to overcome. Fortunately, healthy human brain tissue that can be studied using electron microscopy is sometimes donated after death. Using these donations could improve the understanding of the synapses in normal brains and possible changes associated with disease. Now, Montero-Crespo et al. have mapped synapses in the normal human hippocampus in three dimensions – providing the first detailed description of synaptic structure in this part of the brain. Using high-powered electron microscopes and donated brain tissue samples collected after death, Montero-Crespo et al. imaged almost 25,000 connections between neurons. The analysis showed that synapses were more densely packed in some layers of the hippocampus than in others. Most synapses were found to be connected to tiny dendritic ‘spines’ that sprout from dendritic branches of the neuron, and they activated (not suppressed) the next neuron. Beyond its implications for better understanding of brain health and disease, this work could also advance computer modelling attempts to mimic the structure of the brain and its activity.This study was funded by grants from the Spanish “Ministerio de Ciencia e Innovación” (grant PGC2018-094307-B-I00), Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain, CB06/05/0066), the Alzheimer’s Association (ZEN-15-321663) and the Universidad Nacional de Educación a Distancia (UNED, Spain, Plan de Promoción de la Investigación, 2014-040-UNED-POST). M.M-C. was awarded a research fellowship from the Spanish “Ministerio de Educación, Cultura y Deporte” (contract FPU14/02245).Peer reviewedeLife Sciences PublicationsMinisterio de Ciencia e Innovación (España)Alzheimer's AssociationCentro Investigación Biomédica en Red Enfermedades Neurodegenerativas (España)Universidad Nacional de Educación a Distancia (España)Ministerio de Educación, Cultura y Deporte (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/229381reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN//PGC2018-094307-B-I00http://dx.doi.org/10.7554/eLife.57013Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2293812026-05-22T06:33:51Z
score 15,811543

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