Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

Nature Nanotechnology, Год журнала: 2023, Номер 18(10), С. 1241 - 1251

Опубликована: Июль 10, 2023

Abstract Crossing the blood–brain barrier in primates is a major obstacle for gene delivery to brain. Adeno-associated viruses (AAVs) promise robust, non-invasive from bloodstream However, unlike rodents, few neurotropic AAVs efficiently cross non-human primates. Here we report on AAV.CAP-Mac, an engineered variant identified by screening adult marmosets and newborn macaques, which has improved efficiency brains of multiple primate species: marmoset, rhesus macaque green monkey. CAP-Mac neuron biased infant Old World primates, exhibits broad tropism macaques vasculature marmosets. We demonstrate applications single, intravenous dose deliver functional GCaMP ex vivo calcium imaging across brain areas, or cocktail fluorescent reporters Brainbow-like labelling throughout brain, circumventing need germline manipulations As such, shown have potential systemic transfer

Язык: Английский

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Common fronto-temporal effective connectivity in humans and monkeys

Neuron, Год журнала: 2021, Номер 109(5), С. 852 - 868.e8

Опубликована: Янв. 21, 2021

Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging visualize the effects of direct electrical stimulation in macaque monkeys human neurosurgery patients. discovered comparable caudal auditory cortex both ventro-lateral prefrontal (VLPFC, including area 44) parahippocampal species. Human-specific differences were clearest form stronger hemispheric lateralization effects. In humans, tractography revealed remarkably rapid evoked potentials VLPFC following speech sounds drove VLPFC, consistent with prior evidence projections homologous vocalization-responsive regions. The results identify a common signature nonhuman primates, which from appears equally indirect hippocampus.Video Abstracthttps://www.cell.com/cms/asset/0cb19785-ae66-4024-baaf-2dce151c2412/mmc5.mp4Loading ...(mp4, 19.89 MB) Download video

Язык: Английский

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The Subcortical Atlas of the Rhesus Macaque (SARM) for neuroimaging

NeuroImage, Год журнала: 2021, Номер 235, С. 117996 - 117996

Опубликована: Март 29, 2021

Digitized neuroanatomical atlases that can be overlaid onto functional data are crucial for localizing brain structures and analyzing networks identified by neuroimaging techniques. To aid in structural analysis, we have created a comprehensive parcellation of the rhesus macaque subcortex using high-resolution ex vivo imaging scan. This anatomical scan its were warped to updated NIMH Macaque Template (NMT v2), an population template, where was refined produce Subcortical Atlas Rhesus (SARM) with 210 primary regions-of-interest (ROIs). The subcortical nomenclature reflect those 4th edition Monkey Brain Stereotaxic Coordinates (Paxinos et al., preparation), rather than proposing yet another novel atlas. ROIs organized across six spatial hierarchical scales from small, fine-grained broader composites multiple ROIs, making SARM suitable analysis at different resolutions allowing labeling signals when more accurate localization is not possible. As example application this atlas, included localizer dorsal lateral geniculate (DLG) nucleus three macaques visual flickering checkerboard stimulus, identifying quantifying significant fMRI activation atlas region. has been made openly available community easily used common MRI processing software, such as AFNI, embedded into software alongside cortical atlases.

Язык: Английский

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The Digital Brain Bank, an open access platform for post-mortem imaging datasets

eLife, Год журнала: 2022, Номер 11

Опубликована: Март 17, 2022

Post-mortem magnetic resonance imaging (MRI) provides the opportunity to acquire high-resolution datasets investigate neuroanatomy and validate origins of image contrast through microscopy comparisons. We introduce Digital Brain Bank ( open.win.ox.ac.uk/DigitalBrainBank ), a data release platform providing open access curated, multimodal post-mortem neuroimaging datasets. Datasets span three themes —Digital Neuroanatomist : for detailed neuroanatomical investigations; Zoo comparative neuroanatomy; Pathologist neuropathology investigations. The first includes 21 distinctive whole-brain diffusion MRI structural connectivity investigations, alongside complementary modalities. This one highest-resolution human ever acquired, in fourteen nonhuman primate species, largest cohort studies neurodegeneration. is culmination our lab’s investment into methodology MRI-microscopy analysis techniques. manuscript overview work with date, including development methods large samples, whole, brains. Taken together, cross-scale, cross-species facilitating incorporation studies.

Язык: Английский

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Mapping and comparing fMRI connectivity networks across species

Communications Biology, Год журнала: 2023, Номер 6(1)

Опубликована: Дек. 7, 2023

Abstract Technical advances in neuroimaging, notably fMRI, have allowed distributed patterns of functional connectivity to be mapped the human brain with increasing spatiotemporal resolution. Recent years seen a growing interest extending this approach rodents and non-human primates understand mechanism fMRI complement investigations connectome. Here, we discuss current challenges opportunities mapping across species. We underscore critical importance physiologically decoding neuroimaging measures (dys)connectivity via multiscale mechanistic animals. next highlight set general principles governing organization mammalian networks These include presence evolutionarily conserved network systems, dominant cortical axis connectivity, common repertoire topographically modes. finally describe emerging approaches allowing comparisons extrapolations findings As neuroscientists gain access increasingly sophisticated perturbational, computational recording tools, cross-species offers novel investigate large-scale health disease.

Язык: Английский

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The coming decade of digital brain research: A vision for neuroscience at the intersection of technology and computing

Imaging Neuroscience, Год журнала: 2024, Номер 2, С. 1 - 35

Опубликована: Апрель 1, 2024

Abstract In recent years, brain research has indisputably entered a new epoch, driven by substantial methodological advances and digitally enabled data integration modelling at multiple scales—from molecules to the whole brain. Major are emerging intersection of neuroscience with technology computing. This science combines high-quality research, across scales, culture multidisciplinary large-scale collaboration, translation into applications. As pioneered in Europe’s Human Brain Project (HBP), systematic approach will be essential for meeting coming decade’s pressing medical technological challenges. The aims this paper to: develop concept decade digital discuss community large, identify points convergence, derive therefrom scientific common goals; provide framework current future development EBRAINS, infrastructure resulting from HBP’s work; inform engage stakeholders, funding organisations institutions regarding research; address transformational potential comprehensive models artificial intelligence, including machine learning deep learning; outline collaborative that integrates reflection, dialogues, societal engagement on ethical opportunities challenges as part research.

Язык: Английский

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A collaborative resource platform for non-human primate neuroimaging

NeuroImage, Год журнала: 2020, Номер 226, С. 117519 - 117519

Опубликована: Ноя. 20, 2020

Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted use with NHPs or other animals, which has led an abundance custom, in-house solutions. In recent years, the global NHP community made significant efforts transform towards more open and collaborative practices. Here we present PRIMatE Resource Exchange (PRIME-RE), new online platform neuroimaging. PRIME-RE dynamic community-driven hub exchange practical knowledge, analytical tools, data repositories, specifically related caters both researchers developers who are either field, looking stay abreast latest developments, seeking collaboratively advance .

Язык: Английский

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The cortical connectome of primate lateral prefrontal cortex

Neuron, Год журнала: 2021, Номер 110(2), С. 312 - 327.e7

Опубликована: Ноя. 4, 2021

The lateral prefrontal cortex (LPFC) of primates plays an important role in executive control, but how it interacts with the rest remains unclear. To address this, we densely mapped cortical connectome LPFC, using electrical microstimulation combined functional MRI (EM-fMRI). We found isomorphic mappings between LPFC and five major processing domains composing most cerebral except early sensory motor areas. An grid ∼200 stimulation sites topographically to separate grids activation domains, coarsely resembling visual maps retina. temporal parietal largely overlapped suggesting organized convergence ventral dorsal streams, other at least partially. Thus, contains overlapping, millimeter-scale that mirror organization supporting LPFC's coordinating activity within across these domains.

Язык: Английский

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Comparative connectomics of the primate social brain

NeuroImage, Год журнала: 2021, Номер 245, С. 118693 - 118693

Опубликована: Окт. 31, 2021

Social interaction is thought to provide a selection pressure for human intelligence, yet little known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of structure, function, connectivity humans non-human primates (NHPs), leading nascent field comparative connectomics. However, linking social behavior organization across remains challenging. Here, we review current understanding macroscale neural mechanisms behaviors from viewpoint system neuroscience. We first demonstrate an association between number cortical neurons size groups primates, suggesting link information-processing capacity capabilities. Moreover, by capitalizing on recent species-harmonized functional MRI, that portions mirror neuron default-mode networks, which are be important representation other's actions sense self, respectively, exhibit similarities macaque monkeys humans, possible homologies. With respect these two describe developments neurobiology perception, joint attention, personality complexity. Together, Human Connectome Project (HCP)-style neuroimaging, hyperscanning, behavioral, other multi-modal investigations expected yield insights into evolutionary foundations behavior.

Язык: Английский

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Toward next-generation primate neuroscience: A collaboration-based strategic plan for integrative neuroimaging

Neuron, Год журнала: 2021, Номер 110(1), С. 16 - 20

Опубликована: Ноя. 3, 2021

Язык: Английский

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