A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics DOI Creative Commons
Yuri Elias Rodrigues, Cezar M. Tigaret, Hélène Marie

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Авг. 17, 2023

Discovering the rules of synaptic plasticity is an important step for understanding brain learning. Existing models are either (1) top-down and interpretable, but not flexible enough to account experimental data, or (2) bottom-up biologically realistic, too intricate interpret hard fit data. To avoid shortcomings these approaches, we present a new rule based on geometrical readout mechanism that flexibly maps enzyme dynamics predict outcomes. We apply this multi-timescale model hippocampal induction includes electrical dynamics, calcium, CaMKII calcineurin, accurate representation intrinsic noise sources. Using single set parameters, demonstrate robustness by reproducing nine published ex vivo experiments covering various spike-timing frequency-dependent protocols, animal ages, conditions. Our also predicts in vivo-like spike timing irregularity strongly shapes outcome. This modelling approach can be readily applied other excitatory inhibitory synapses discover their rules.

Язык: Английский

The synapse in traumatic brain injury DOI Creative Commons
Aimun A. B. Jamjoom, Jonathan Rhodes, Peter Andrews

и другие.

Brain, Год журнала: 2020, Номер 144(1), С. 18 - 31

Опубликована: Сен. 10, 2020

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide risk factor for dementia later in life. Research into the pathophysiology TBI has focused on impact neuron. However, recent advances have shown that major synapse structure function through combination immediate mechanical insult ensuing secondary processes, to loss. In this review, we highlight role with focus confluence multiple processes including excitotoxicity, inflammation oxidative stress. The primary triggers cascade events each these discuss complex interplay occurs at synapse. We also examine how impacted by traumatic axonal it may play spread tau after TBI. propose astrocytes crucial mediating both loss recovery. Finally, developments field molecular imaging, fluid biomarkers therapeutics. particular, our understanding diversity suggest new technology synaptome mapping prove useful identifying synapses are vulnerable or resistant

Язык: Английский

Процитировано

178
A brainwide atlas of synapses across the mouse life span DOI Open Access
Mélissa Cizeron, Zhen Qiu,

Babis Koniaris

и другие.

Science, Год журнала: 2020, Номер 369(6501), С. 270 - 275

Опубликована: Июнь 11, 2020

Brain synapses through the life span Excitatory connect neurons in brain to build circuits that enable behavior. Cizeron et al. surveyed mouse from birth old age and present data as a community resource, Mouse Lifespan Synaptome Atlas (see Perspective by Micheva ). Molecular morphological features defined 37 subtypes of synapses. Although synapse density generally increased early development declined age, details differed different areas. Science this issue p. 270 ; see also 253

Язык: Английский

Процитировано

166
A metabolome atlas of the aging mouse brain DOI Creative Commons
Jun Ding, Jian Ji, Zachary Rabow

и другие.

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Окт. 15, 2021

Abstract The mammalian brain relies on neurochemistry to fulfill its functions. Yet, the complexity of metabolome and changes during diseases or aging remain poorly understood. Here, we generate a atlas wildtype mouse from 10 anatomical regions spanning adolescence old age. We combine data three assays structurally annotate 1,547 metabolites. Almost all metabolites significantly differ between age groups, but not by sex. A shift in sphingolipid patterns related myelin remodeling is accompanied large other metabolic pathways. Functionally (brain stem, cerebrum cerebellum) are also metabolically similar. In cerebrum, correlations markedly weaken adulthood, whereas at age, cross-region correlation reflect decreased segregation. show that can be mapped existing gene protein atlases. publicly available ( https://mouse.atlas.metabolomics.us/ ) serves as foundation dataset for future metabolomic studies.

Язык: Английский

Процитировано

159
Synapse pathology in Alzheimer’s disease DOI Creative Commons
Jessica Griffiths, Seth G. N. Grant

Seminars in Cell and Developmental Biology, Год журнала: 2022, Номер 139, С. 13 - 23

Опубликована: Июнь 9, 2022

Synapse loss and damage are central features of Alzheimer's disease (AD) contribute to the onset progression its behavioural physiological features. Here we review literature describing synapse pathology in AD, from what have learned microscopy terms impacts on architecture, mechanistic role Aβ, tau glial cells, mitochondrial dysfunction, link with AD risk genes. We consider emerging view that may operate at a further level, diversity, discuss prospects for leveraging new synaptome mapping methods comprehensively understand molecular properties vulnerable resilient synapses. Uncovering brain diversity should inform therapeutic approaches targeted preserving or replenishing lost damaged synapses aid interpretation clinical imaging aim measure damage.

Язык: Английский

Процитировано

119
Droplet-based transcriptome profiling of individual synapses DOI
Muchun Niu, Wenjian Cao, Yongcheng Wang

и другие.

Nature Biotechnology, Год журнала: 2023, Номер 41(9), С. 1332 - 1344

Опубликована: Янв. 16, 2023

Язык: Английский

Процитировано

45
The aging mouse brain: cognition, connectivity and calcium DOI Creative Commons
Carola I. Radulescu, Veronika Cerar, Peter Haslehurst

и другие.

Cell Calcium, Год журнала: 2021, Номер 94, С. 102358 - 102358

Опубликована: Янв. 23, 2021

Aging is a complex process that differentially impacts multiple cognitive, sensory, neuronal and molecular processes. Technological innovations now allow for parallel investigation of circuit function, structure composition in the brain awake behaving adult mice. Thus, mice have become critical tool to better understand how aging brain. However, more granular systems-based approach, which considers impact age on key features relating neural processing, required. Here, we review evidence probing mouse We focus range processes including cognitive abilities, sensory systems, synaptic plasticity calcium regulation. Across many find prominent age-related dysregulation even before 12 months age, suggesting emerging alterations can manifest by late adulthood. also reports some are remarkably resilient aging. The suggests does not drive parallel, linear all but instead earlier, severely, than others. propose capturing fine-scale vulnerability resilience may provide opportunities rejuvenation aged

Язык: Английский

Процитировано

72
A brain atlas of synapse protein lifetime across the mouse lifespan DOI Creative Commons
Edita Bulovaite, Zhen Qiu,

Maximilian Kratschke

и другие.

Neuron, Год журнала: 2022, Номер 110(24), С. 4057 - 4073.e8

Опубликована: Окт. 5, 2022

The lifetime of proteins in synapses is important for their signaling, maintenance, and remodeling, memory duration. We quantified the endogenous PSD95, an abundant postsynaptic protein excitatory synapses, at single-synapse resolution across mouse brain lifespan, generating Protein Lifetime Synaptome Atlas. Excitatory have a wide range PSD95 lifetimes extending from hours to several months, with distinct spatial distributions dendrites, neurons, regions. Synapses short are enriched young animals regions controlling innate behaviors, whereas long accumulate during development, cortex CA1 where memories stored, preferentially preserved old age. Synapse increases throughout model autism schizophrenia. adds further layer synapse diversity enriches prevailing concepts aging, disease.

Язык: Английский

Процитировано

69
Towards a biologically annotated brain connectome DOI
Vincent Bazinet, Justine Y. Hansen, Bratislav Mišić

и другие.

Nature reviews. Neuroscience, Год журнала: 2023, Номер 24(12), С. 747 - 760

Опубликована: Окт. 17, 2023

Язык: Английский

Процитировано

41
Merged magnetic resonance and light sheet microscopy of the whole mouse brain DOI Creative Commons
G. Allan Johnson, Yuqi Tian, David G. Ashbrook

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(17)

Опубликована: Апрель 17, 2023

We have developed workflows to align 3D magnetic resonance histology (MRH) of the mouse brain with light sheet microscopy (LSM) and delineations same specimen. start MRH in skull gradient echo diffusion tensor imaging (DTI) at 15 μm isotropic resolution which is ~ 1,000 times higher than that most preclinical MRI. Connectomes are generated superresolution tract density images ~5 μm. Brains cleared, stained for selected proteins, imaged by LSM 1.8 μm/pixel. data registered into reference space labels derived from ABA common coordinate framework. The result a hi gh- d imensional i ntegrated v olum e r egistration ( HiDiver ) alignment precision better 50 µm. Throughput sufficiently high being used quantitative studies impact gene variants aging on cytoarchitecture connectomics.

Язык: Английский

Процитировано

38
Synaptoneurolipidomics: lipidomics in the study of synaptic function DOI Creative Commons
Robert Ahrends, Shane R. Ellis, Steven H. L. Verhelst

и другие.

Trends in Biochemical Sciences, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The brain is an exceptionally lipid-rich organ with a very complex lipid composition. Lipids are central in several neuronal processes, including membrane formation and fusion, myelin packing, lipid-mediated signal transmission. Lipid diversity associated the evolution of higher cognitive abilities primates, affected by activity, instrumental for synaptic plasticity, illustrating that lipids not static components membranes. Several lines evidence suggest composition synapses unique distinct from other subcompartments. Here, we delve into nascent field synaptoneurolipidomics, offering overview current knowledge on junctions technological advances will allow us to study impact function.

Язык: Английский

Процитировано

2