Age-Related Synaptic Signatures of Brain and Cognitive Reserve in the Rat Hippocampus and Parahippocampal Regions

Neurobiology of Aging, Год журнала: 2025, Номер 148, С. 80 - 97

Опубликована: Фев. 7, 2025

Age-related cognitive decline varies widely among individuals, with some showing resilience despite older age. This study examines synaptic markers of glutamatergic and GABAergic neurotransmission in the hippocampus cortex rats differing abilities, aiming to uncover mechanisms that contribute resilience. We observed significant age-related reductions vesicular glutamate transporter VGluT1, particularly stratum oriens (SO), radiatum (SR), lacunosum-moleculare (SLM) dorsal CA3 SLM CA1. Furthermore, loss VGluT1 CA3-SLM correlated severity memory impairment. Higher levels GABA (VGAT) were associated better spatial learning rats, across several zones hippocampus, including outer molecular layer dentate gyrus (DG), SO, SR, SLM, pyramidal cell layers both suggests enhanced inhibitory specific aspect may protect against decline. While showed consistent age- memory-related changes, ventral remained largely intact. In perirhinal cortex, declined no changes VGAT, while unchanged other cortical regions, lateral entorhinal, retrosplenial, posterior parietal cortices. These findings highlight region-specific patterns aging as potential brain reserve.

Язык: Английский

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Synaptic architecture of a memory engram in the mouse hippocampus

Science, Год журнала: 2025, Номер 387(6740)

Опубликована: Март 20, 2025

Memory engrams are formed through experience-dependent plasticity of neural circuits, but their detailed architectures remain unresolved. Using three-dimensional electron microscopy, we performed nanoscale reconstructions the hippocampal CA3-CA1 pathway after chemogenetic labeling cellular ensembles recruited during associative learning. Neurons with a remote history activity coinciding memory acquisition showed no strong preference for wiring each other. Instead, connectomes expanded multisynaptic boutons independently coactivation state postsynaptic partners. The rewiring representing an initial engram was accompanied by input-specific, spatially restricted upscaling individual synapses, as well remodeling mitochondria, smooth endoplasmic reticulum, and interactions astrocytes. Our findings elucidate physical hallmarks long-term offer structural basis flexibility information coding.

Язык: Английский

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Integrating multimodal data to understand cortical circuit architecture and function

Nature Neuroscience, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

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CAVE: Connectome Annotation Versioning Engine

Nature Methods, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Abstract Advances in electron microscopy, image segmentation and computational infrastructure have given rise to large-scale richly annotated connectomic datasets, which are increasingly shared across communities. To enable collaboration, users need be able concurrently create annotations correct errors the automated by proofreading. In large every proofreading edit relabels cell identities of millions voxels thousands like synapses. For analysis, require immediate reproducible access this changing expanding data landscape. Here we present Connectome Annotation Versioning Engine (CAVE), a that provides scalable solutions for flexible annotation support fast analysis queries at arbitrary time points. Deployed as suite web services, CAVE empowers distributed communities perform connectome up petascale datasets (~1 mm 3 ) while annotating is ongoing.

Язык: Английский

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Multi-scale spiking network model of human cerebral cortex

Cerebral Cortex, Год журнала: 2024, Номер 34(10)

Опубликована: Окт. 1, 2024

Abstract Although the structure of cortical networks provides necessary substrate for their neuronal activity, alone does not suffice to understand activity. Leveraging increasing availability human data, we developed a multi-scale, spiking network model cortex investigate relationship between and dynamics. In this model, each area in one hemisphere Desikan–Killiany parcellation is represented by $1\,\mathrm{mm^{2}}$ column with layered structure. The aggregates data across multiple modalities, including electron microscopy, electrophysiology, morphological reconstructions, diffusion tensor imaging, into coherent framework. It predicts activity on all scales from single-neuron area-level functional connectivity. We compared electrophysiological resting-state magnetic resonance imaging (fMRI) data. This comparison reveals that can reproduce aspects both statistics fMRI correlations if inter-areal connections are sufficiently strong. Furthermore, study propagation single-spike perturbation macroscopic fluctuations through network. open-source serves as an integrative platform further refinements future silico studies structure, dynamics, function.

Язык: Английский

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A scalable and modular automated pipeline for stitching of large electron microscopy datasets

eLife, Год журнала: 2022, Номер 11

Опубликована: Июль 26, 2022

Serial-section electron microscopy (ssEM) is the method of choice for studying macroscopic biological samples at extremely high resolution in three dimensions. In nervous system, nanometer-scale images are necessary to reconstruct dense neural wiring diagrams brain, so -called connectomes . The data that can comprise up 10 8 individual EM must be assembled into a volume, requiring seamless 2D registration from physical section followed by 3D alignment stitched sections. throughput ssEM necessitates stitching done pace imaging, which currently produces tens terabytes per day. To achieve this, we present modular volume assembly software pipeline ASAP (Assembly Stitching and Alignment Pipeline) scalable datasets containing petabytes parallelized work distributed computational environment. built on top Render Trautman Saalfeld (2019) services used brain adult Drosophila melanogaster (Zheng et al. 2018). It achieves operating only image meta-data transformations. modular, allowing easy incorporation new algorithms without significant changes workflow. entire includes complete set tools stitching, automated quality control, alignment, final rendering disk. has been deployed continuous several large-scale mouse visual cortex human including one cubic millimeter (Yin 2020); Microns Consortium (2021) speeds exceed imaging. also multi-channel processing capabilities applied fluorescence multi-modal like array tomography.

Язык: Английский

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Amyotrophic lateral sclerosis represents corticomotoneuronal system failure

Muscle & Nerve, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 7, 2024

Several decades have passed since the anterograde corticomotoneuronal hypothesis for amyotrophic lateral sclerosis (ALS) was proposed. The intervening years witnessed its emergent support based on anatomical, pathological, physiological, neuroimaging, and molecular biological studies. evolution of an extensive system appears restricted to human species, with ALS representing a uniquely disease. While some, very select non-human primates limited projections, these tend be absent in all other animals. From general perspective, early clinical features may considered reflect failure system. characteristic loss skilled motor dexterity involving limbs, speech impairment through progressive bulbar dysfunction specifically involve those units having strongest projections. A similar explanation likely underlies unique "split phenotypes" that now been well characterized ALS. Large Betz cells pyramidal projecting neurons, their dendritic arborization, are particularly vulnerable elements exposome such as aging, environmental stress lifestyle changes. Progressive proteosome impairs nucleocytoplasmic shuffling induces toxic but soluble TDP-43 aggregate corticomotoneurons. cell is further accentuated profuse arborizations. Clarification specific genomes neural networks will promote initiation precision medicine approaches directed key structure neurological manifestations ALS,

Язык: Английский

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Unveiling universal aspects of the cellular anatomy of the brain

Communications Physics, Год журнала: 2024, Номер 7(1)

Опубликована: Июнь 10, 2024

Язык: Английский

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Differential cortical layer engagement during seizure initiation and spread in humans

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 17, 2024

Abstract Despite decades of research, we still do not understand how spontaneous human seizures start and spread – especially at the level neuronal microcircuits. In this study, used laminar arrays micro-electrodes to simultaneously record local field potentials multi-unit neural activities across six layers neocortex during focal in humans. We found that, within ictal onset zone, discharges generated a seizure consisted current sinks sources only infra-granular granular layers. Outside reflected flow supra-granular Interestingly, these patterns evolved course outside zone where superficial extended into deeper Based on observations, framework describing cortical-cortical dynamics is proposed with implications for localization, surgical targeting, neuromodulation techniques block generation propagation seizures.

Язык: Английский

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Multiplexed volumetric CLEM enabled by scFvs provides insights into the cytology of cerebellar cortex

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 5, 2024

Abstract Mapping neuronal networks is a central focus in neuroscience. While volume electron microscopy (vEM) can reveal the fine structure of (connectomics), it does not provide molecular information to identify cell types or functions. We developed an approach that uses fluorescent single-chain variable fragments (scFvs) perform multiplexed detergent-free immunolabeling and volumetric-correlated-light-and-electron-microscopy on same sample. generated eight scFvs targeting brain markers. Six probes were imaged cerebellum female mouse, using confocal with spectral unmixing, followed by vEM The results excellent ultrastructure superimposed multiple fluorescence channels. Using this approach, we documented poorly described type, two mossy fiber terminals, subcellular localization one type ion channel. Because be derived from existing monoclonal antibodies, hundreds such enable overlays for connectomic studies.

Язык: Английский

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