Article
Clinical Neurology
Marta Montero-Crespo, Marta Dominguez-Alvaro, Lidia Alonso-Nanclares, Javier DeFelipe, Lidia Blazquez-Llorca
Summary: Alzheimer's disease is a common form of dementia characterized by cognitive impairment, with extracellular protein deposits and abnormal protein accumulation in neurons. Synaptic alterations were found in different stages of the disease, with more severe changes observed in late-stage cases.
Article
Clinical Neurology
Marta Montero-Crespo, Marta Dominguez-Alvaro, Lidia Alonso-Nanclares, Javier DeFelipe, Lidia Blazquez-Llorca
Summary: Alzheimer's disease is a common form of dementia characterized by persistent and progressive impairment of cognitive functions. Early-stage cases show normal synaptic morphology, but late-stage cases experience decreased synaptic density and morphological alterations.
Article
Biochemical Research Methods
Lucy M. Collinson, Carles Bosch, Anwen Bullen, Jemima J. Burden, Raffaella Carzaniga, Cheng Cheng, Michele C. Darrow, Georgina Fletcher, Errin Johnson, Kedar Narayan, Christopher J. Peddie, Martyn Winn, Charles Wood, Ardan Patwardhan, Gerard J. Kleywegt, Paul Verkade
Summary: Volume electron microscopy (vEM) is a set of techniques that can reveal the 3D structure of cells and tissues at depths of at least 1 micrometer. An emerging grassroots community effort is rapidly showcasing the impact of vEM technology in life sciences and clinical research.
Article
Endocrinology & Metabolism
Eleonora Napoli, Alexios A. Panoutsopoulos, Patricia Kysar, Nathaniel Satriya, Kira Sterling, Bradley Shibata, Denise Imai, David N. Ruskin, Konstantinos S. Zarbalis, Cecilia Giulivi
Summary: Autophagy is crucial for cell function, recycling intracellular components during starvation and eliminating spent organelles and proteins. Wdfy3 is a scaffold protein linked to intellectual disability, neurodevelopment delay, and autism spectrum disorder, and its haploinsufficiency in mice results in decreased mitophagy and affects synaptic function and glycogen synthesis.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Biology
Sven Dorkenwald, Nicholas L. Turner, Thomas Macrina, Kisuk Lee, Ran Lu, Jingpeng Wu, Agnes L. Bodor, Adam A. Bleckert, Derrick Brittain, Nico Kemnitz, William M. Silversmith, Dodam Ih, Jonathan Zung, Aleksandar Zlateski, Ignacio Tartavull, Szi-Chieh Yu, Sergiy Popovych, William Wong, Manuel Castro, Chris S. Jordan, Alyssa M. Wilson, Emmanouil Froudarakis, JoAnn Buchanan, Marc M. Takeno, Russel Torres, Gayathri Mahalingam, Forrest Collman, Casey M. Schneider-Mizell, Daniel J. Bumbarger, Yang Li, Lynne Becker, Shelby Suckow, Jacob Reimer, Andreas S. Tolias, Nuno Macarico da Costa, R. Clay Reid, H. Sebastian Seung
Summary: Learning from experience depends on changes in neuronal connections. In this study, the authors present a large map of connectivity between cortical neurons in the mouse primary visual cortex and use it to identify constraints on learning algorithms used by the cortex. They find that synapse size, specifically between layer 2/3 pyramidal cells, can be modeled as a combination of a binary variable and an analog variable drawn from a log-normal distribution. The binary variables of two synapses are highly correlated, while the analog variables are not.
Article
Neurosciences
Vladan Lucic
Summary: This article reviews the importance of electron microscopy in the study of neuronal synapse structures and discusses the use of image processing software methods. Special attention is given to the application of recent cryo-electron microscopy and tomography methods in molecular level analysis.
CURRENT OPINION IN NEUROBIOLOGY
(2022)
Article
Virology
Gabriela N. Condezo, Carmen San Martin
Summary: The localization of viral nucleic acids in the cell is crucial for understanding the infectious cycle. By using nucleotide analogs such as BrdU, researchers can accurately distinguish between host and viral DNA during replication or transcription. Proper experimental conditions and methodological variations are necessary to ensure effective incorporation of labeling agents and accurate viral genome localization in infected cells.
Article
Biochemical Research Methods
Philipp J. Schubert, Sven Dorkenwald, Michal Januszewski, Jonathan Klimesch, Fabian Svara, Andrei Mancu, Hashir Ahmad, Michale S. Fee, Viren Jain, Joergen Kornfeld
Summary: SyConn2 is an open-source toolkit for inferring and analyzing the connectomes in brain tissue using machine learning. It supports large datasets, provides a visualization interface, and allows for complex queries.
Article
Chemistry, Multidisciplinary
Ching-Che Lin, Shih-Ming Wang, Bo-Yi Chen, Cheng-Hung Chi, I-Ling Chang, Chih-Wei Chang
Summary: Recent developments in nanoscale thermal metrology using electron microscopy have shown impressive advancements. This study considers the potential of this technology in material analysis and introduces a direct thermal absorbance measurement platform for atomic number analysis at nanoscales.
Article
Cell Biology
Joshua B. Melander, Aran Nayebi, Bart C. Jongbloets, Dale A. Fortin, Maozhen Qin, Surya Ganguli, Tianyi Mao, Haining Zhong
Summary: Cortical function relies on balanced activation of excitatory and inhibitory neurons. The organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneurons are not well understood. Studies show that synapses onto PV+ neurons are less variable and more stable.
Article
Dermatology
Ross Laws, David H. Steel, Neil Rajan
Summary: Volume scanning electron microscopy (VSEM) is a microscopy technique used for qualitative and quantitative analysis of cells and organelles within tissues. It involves serial sectioning and imaging, followed by segmentation and three-dimensional reconstruction using computer software packages, allowing visualization of 3D structures.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Cell Biology
Sergey Loginov, Job Fermie, Jantina Fokkema, Alexandra Agronskaia, Cilia De Heus, Gerhard A. Blab, Judith Klumperman, Hans C. Gerritsen, Nalan Liv
Summary: Intracellular processes require precise organization of proteins and organelles. Volume-CLEM, a combination of light and electron microscopy, offers a unique approach to study cellular physiology at a high-resolution ultrastructural level. However, limitations in throughput and 3D correlation efficiency have hindered its application. In this study, researchers developed a novel pipeline for volume-CLEM that addresses these limitations by using fiducial nanoparticles and an integrated confocal fluorescence microscope and scanning electron microscope. They demonstrated the power of this approach by targeting rare and transient contact sites between organelles, providing valuable insights into cellular dynamics and ultrastructural details.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jason Seth Rothman, Carolina Borges-Merjane, Noemi Holderith, Peter Jonas, R. Angus Silver
Summary: Stereological methods are crucial in estimating the 3D particle size and density from 2D projections, but they are prone to errors due to undetected particle profiles. The Keiding model, proposed in 1972, offers a potential solution by accounting for lost caps. However, this model has not been widely adopted or tested.
Article
Biochemistry & Molecular Biology
Cristine De Paula Nascimento-Castro, Elisa C. Winkelmann-Duarte, Gianni Mancini, Priscilla Gomes Welter, Evelini Placido, Marcelo Farina, Joana Gil-Mohapel, Ana Lucia S. Rodrigues, Andreza Fabro de Bem, Patricia S. Brocardo
Summary: Huntington's disease is a genetic neurodegenerative disease that affects motor, psychiatric, and cognitive functions. Recent evidence suggests that the emotional and cognitive deficits observed in patients with HD might be associated with hippocampal dysfunction. In this study using a HD mouse model, researchers found that mice in the late symptomatic stage exhibited depressive-like behavior and cognitive deficits. Additionally, they observed degenerative changes in the hippocampal dentate gyrus, including the presence of dark neurons and structural alterations in the rough endoplasmic reticulum and Golgi apparatus.
Review
Biochemistry & Molecular Biology
Martin Sachse, Isabel Fernandez de Castro, Raquel Tenorio, Cristina Risco
Summary: Transmission electron microscopy (TEM) is essential for studying virus-cell interactions. Immunogold and metal-tagging transmission electron microscopy (METTEM) are two widely used labeling methods that contribute to the study of viral infections. Immunogold utilizes antibodies and electron dense gold particles while METTEM uses metallothionein (MT) as a clonable tag. Together, these methods provide a powerful tool for investigating virus-cell interactions.
MOLECULAR MICROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ahmed Eltokhi, Andrea Santuy, Angel Merchan-Perez, Rolf Sprengel
Summary: The correlation between dysfunction in the glutamatergic system and neuropsychiatric disorders, including schizophrenia and autism spectrum disorder, is discussed in this review. The alterations in synaptic plasticity and ultrastructural changes in synapses in these disorders are highlighted, with a brief mention of the potential reversibility of these conditions based on regular synaptic physiology findings.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Hematology
Marta Rodriguez, Ruth Alonso-Alonso, Laura Tomas-Roca, Socorro M. Rodriguez-Pinilla, Rebeca Manso-Alonso, Laura Cereceda, Jennifer Borregon, Teresa Villaescusa, Raul Cordoba, Margarita Sanchez-Beato, Ismael Fernandez-Miranda, Isabel Betancor, Carmen Barcena, Juan F. Garcia, Manuela Mollejo, Monica Garcia-Cosio, Paloma Martin-Acosta, Fina Climent, Dolores Caballero, Lorena de la Fuente, Pablo Minguez, Linda Kessler, Catherine Scholz, Antonio Gualberto, Rufino Mondejar, Miguel A. Piris
Summary: This study analyzed cases of Peripheral T-cell lymphoma (PTCL) to identify specific gene sets associated with different histological types, supporting the division of PTCL into 3 categories and identifying B-cell gene expression as an independent prognostic factor for AITL. The study also highlighted the importance of mutational profiles, with differences in RHOA mutations among the PTCL classes.
Article
Clinical Neurology
Matthew J. Broadhead, Calum Bonthron, Julia Waddington, William Smith, Maite F. Lopez, Sarah Burley, Jessica Valli, Fei Zhu, Noboru H. Komiyama, Colin Smith, Seth G. N. Grant, Gareth B. Miles
Summary: Tripartite synaptopathy is a key hallmark of ALS, as revealed by extensive microscopy-based investigations in ALS model mice and post-mortem human tissue. This study demonstrates widespread synaptic changes and selective loss of tripartite synapses in ALS.
ACTA NEUROPATHOLOGICA
(2022)
Article
Anatomy & Morphology
Marta Turegano-Lopez, Andrea Santuy, Asta Kastanauskaite, Jose-Rodrigo Rodriguez, Javier DeFelipe, Angel Merchan-Perez
Summary: The structural complexity of nervous tissue makes it difficult to unravel the connectivity between neural elements. This article presents an effective method for 3D reconstruction of subcellular structures using single-neuron labeling in fixed tissue. This method allows for mapping of synaptic connectivity and analysis of the surrounding neuropil's ultrastructural features.
FRONTIERS IN NEUROANATOMY
(2022)
Article
Neurosciences
Katrin Amunts, Javier DeFelipe, Cyriel Pennartz, Alain Destexhe, Michele Migliore, Philippe Ryvlin, Steve Furber, Alois Knoll, Lise Bitsch, Jan G. Bjaalie, Yannis Ioannidis, Thomas Lippert, Maria V. Sanchez-Vives, Rainer Goebel, Viktor Jirsa
Summary: Understanding the human brain is a Grand Challenge for 21st century research. Computational approaches and dynamic generative multiscale models are instrumental for linking brain structure and function. The intersection of neuroscience, computing, and robotics has the potential to advance neuro-inspired technologies. To facilitate research sharing and collaboration, the Human Brain Project has launched the digital neuroscience research infrastructure EBRAINS.
Review
Cell Biology
Jessica Griffiths, Seth G. N. Grant
Summary: Synapse loss and damage are key factors in the development of Alzheimer's disease, and this article reviews the literature on synapse pathology in AD, from its impact on synapse architecture to the role of A beta, tau, and glial cells. It also discusses the potential of new mapping methods to understand the molecular properties of vulnerable and resilient synapses and the importance of this knowledge for therapeutic approaches and clinical imaging.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Neurosciences
Edita Bulovaite, Zhen Qiu, Maximilian Kratschke, Adrianna Zgraj, David G. Fricker, Eleanor J. Tuck, Ragini Gokhale, Babis Koniaris, Shekib A. Jami, Paula Merino-Serrais, Elodie Husi, Lorena Mendive-Tapia, Marc Vendrell, Thomas J. O'Dell, Javier DeFelipe, Noboru H. Komiyama, Anthony Holtmaat, Erik Fransen, Seth G. N. Grant
Summary: This study quantified the lifetime of endogenous PSD95 in synapses and generated the Protein Lifetime Synaptome Atlas. It found that protein lifetime in synapses varies with age, brain regions, and memory duration, and that it increases in mouse models of autism and schizophrenia.
Article
Chemistry, Multidisciplinary
Fabio de Moliner, Zuzanna Konieczna, Lorena Mendive-Tapia, Rebecca S. Saleeb, Katie Morris, Juan Antonio Gonzalez-Vera, Takeshi Kaizuka, Seth G. N. Grant, Mathew H. Horrocks, Marc Vendrell
Summary: The multiple applications of super-resolution microscopy have led to the need for minimally invasive labeling strategies for peptide-guided fluorescence imaging. In this study, we have built a library of benzodiazole amino acids and examined their potential as background-free fluorescence microscopy probes. The results show that benzodiazole amino acids retain the binding capabilities of bioactive peptides and exhibit excellent signal-to-background ratios.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Neurosciences
Lidia Alonso-Nanclares, J. Rodrigo Rodriguez, Angel Merchan-Perez, Juncal Gonzalez-Soriano, Sergio Plaza-Alonso, Nicolas Cano-Astorga, Robert K. K. Naumann, Michael Brecht, Javier DeFelipe
Summary: The study aimed to compare the synaptic characteristics between the small brain of Etruscan shrew and the larger human brain. The findings showed that while some synaptic characteristics are similar, there are significant differences in the number and size of synapses, suggesting adaptations of synaptic circuits to specific functions.
JOURNAL OF COMPARATIVE NEUROLOGY
(2023)
Article
Multidisciplinary Sciences
Laura Tomas-Roca, Zhen Qiu, Erik Fransen, Ragini Gokhale, Edita Bulovaite, David J. Price, Noboru H. Komiyama, Seth G. N. Grant
Summary: Neurodevelopmental disorders of genetic origin delay the acquisition of normal abilities, but the brain possesses the capacity to overcome deficits arising from certain germline mutations. In a mouse model of Pax6 mutation, the molecular composition of excitatory synapses, the development of synapse diversity, and the acquisition of normal synaptome architecture are delayed, interfering with cognitive functions. However, these phenotypes are reversed within a few weeks, restoring synapse diversity and synaptome architecture to the normal developmental trajectory.
NATURE COMMUNICATIONS
(2022)
Article
Neurosciences
Valentina Mercaldo, Barbora Vidimova, Denise Gastaldo, Esperanza Fernandez, Adrian C. Lo, Giulia Cencelli, Giorgia Pedini, Silvia De Rubeis, Francesco Longo, Eric Klann, August B. Smit, Seth G. N. Grant, Tilmann Achsel, Claudia Bagni
Summary: This study investigates the diverse proteome of glutamatergic synapses and its involvement in neurodevelopmental disorders (NDDs), specifically fragile X syndrome (FXS). The researchers demonstrate that the brain region-specific composition of postsynaptic density (PSD) contributes to the manifestation of FXS behavioral phenotypes. In the FXS mouse model, there is an altered association between PSD and actin cytoskeleton in the striatum, resulting in immature dendritic spine morphology and reduced synaptic actin dynamics. Enhancing actin turnover with constitutively active RAC1 improves these deficits and rescues the striatal-driven inflexibility observed in FXS individuals.
Article
Neurosciences
Nicolas Cano-Astorga, Sergio Plaza-Alonso, Javier DeFelipe, Lidia Alonso-Nanclares
Summary: The synaptic organization of the human anterior cingulate and temporopolar cortices was studied using FIB/SEM and revealed that Brodmann areas 24, 21, and ventral area 38 have similar synaptic density and size, whereas dorsal area 38 has the highest density and smallest size. However, the proportion and shapes of excitatory and inhibitory synapses were similar across all regions.
Article
Neurosciences
Matthew J. Broadhead, Ani Ayvazian-Hancock, Katherine Doucet, Owen Kantelberg, Lesley Motherwell, Fei Zhu, Seth G. N. Grant, Mathew H. Horrocks, Gareth B. Miles
Summary: This study characterises the synaptic expression of TDP-43 in the spinal cord of mice using high-resolution and super-resolution microscopy techniques. The findings show that TDP-43 is expressed as nanoscale clusters in approximately half of spinal cord synapses, particularly in synapses associated with VGLUT1-positive presynaptic terminals. Interestingly, there is no difference in the subsynaptic expression of pTDP-43 between the ALS mouse model and healthy controls, despite structural deficits in VGLUT1-associated synapses in the ALS model.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
