Nuno Maçarico da Costa
A5019726696- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Advanced Electron Microscopy Techniques and Applications
- Neuroscience and Neural Engineering
- Visual perception and processing mechanisms
- Photoreceptor and optogenetics research
- Retinal Development and Disorders
- Advanced Memory and Neural Computing
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Systemic Lupus Erythematosus Research
- Cloud Computing and Resource Management
- Fetal and Pediatric Neurological Disorders
- Electron and X-Ray Spectroscopy Techniques
- Genetic and Kidney Cyst Diseases
- Force Microscopy Techniques and Applications
- Image Processing Techniques and Applications
- Cerebrospinal fluid and hydrocephalus
- Atherosclerosis and Cardiovascular Diseases
- Biotin and Related Studies
- Advanced MRI Techniques and Applications
- Electronic Health Records Systems
- bioluminescence and chemiluminescence research
Allen Institute
2015-2024
Allen Institute for Brain Science
2015-2024
Polytechnic Institute of Viseu
2013-2021
Seattle University
2020
University of Zurich
2009-2017
Universidade Católica Portuguesa
2014
ETH Zurich
2009-2014
SIB Swiss Institute of Bioinformatics
2013
Neurons in the developing brain undergo extensive structural refinement as nascent circuits adopt their mature form. This physical transformation of neurons is facilitated by engulfment and degradation axonal branches synapses surrounding glial cells, including microglia astrocytes. However, small size phagocytic organelles complex, highly ramified morphology glia have made it difficult to define contribution these other cell types this crucial process. Here, we used large-scale, serial...
Learning from experience depends at least in part on changes neuronal connections. We present the largest map of connectivity to date between cortical neurons a defined type (layer 2/3 [L2/3] pyramidal cells mouse primary visual cortex), which was enabled by automated analysis serial section electron microscopy images with improved handling image defects (250 × 140 90 μm3 volume). used identify constraints learning algorithms employed cortex. Previous studies modeled continuum synapse sizes...
Mammalian cortex features a vast diversity of neuronal cell types, each with characteristic anatomical, molecular and functional properties. Synaptic connectivity powerfully shapes how type participates in the cortical circuit, but mapping rules at resolution distinct types remains difficult. Here, we used millimeter-scale volumetric electron microscopy 1 to investigate all inhibitory neurons across densely-segmented population 1352 cells spanning layers mouse visual cortex, producing wiring...
Abstract Electron microscopy (EM) is widely used for studying cellular structure and network connectivity in the brain. We have built a parallel imaging pipeline using transmission electron microscopes that scales this technology, implements 24/7 continuous autonomous imaging, enables acquisition of petascale datasets. The suitability architecture large-scale was demonstrated by acquiring volume more than 1 mm 3 mouse neocortex, spanning four different visual areas at synaptic resolution,...
Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average of several interneuron classes, there remains a fundamental lack understanding distribution distinct inhibitory cell types with synaptic resolution, how it relates to properties target cells, affects function. Here, we used large-scale electron microscopy functional imaging address these questions for chandelier cells...
Understanding the relationship between circuit connectivity and function is crucial for uncovering how brain implements computation. In mouse primary visual cortex (V1), excitatory neurons with similar response properties are more likely to be synaptically connected, but previous studies have been limited within V1, leaving much unknown about broader rules. this study, we leverage millimeter-scale MICrONS dataset analyze synaptic functional of individual across cortical layers areas. Our...
The cortical column has been an invaluable concept to explain the functional organization of neocortex. While this idea was born out experiments that cleverly combined electrophysiological recordings with anatomy, no one 'seen' anatomy a column. All we know is when record through cortex primates, ungulates, and carnivores in trajectory perpendicular its surface there remarkable constancy receptive field properties neurons regarding set stimulus features. There obvious morphological analog...
In the cat's visual cortex, responses of simple cells seem to be totally determined by their thalamic input, yet only a few percent excitatory synapses in layer 4 arise from thalamus. To resolve this discrepancy between structure and function, we used correlated light electron microscopy search individual spiny stellate (simple cells) for possible structural features that would explain biophysical efficacy such as synaptic location on dendrites, size postsynaptic densities, targets. We find...
Abstract Learning from experience depends at least in part on changes neuronal connections. We present the largest map of connectivity to date between cortical neurons a defined type (L2/3 pyramidal cells), which was enabled by automated analysis serial section electron microscopy images with improved handling image defects. used identify constraints learning algorithms employed cortex. Previous studies modeled continuum synapse sizes (Arellano et al. 2007) log-normal distribution...
Abstract To understand the brain we must relate neurons’ functional responses to circuit architecture that shapes them. Here, present a large connectomics dataset with dense calcium imaging of millimeter scale volume. We recorded activity from approximately 75,000 neurons in primary visual cortex (VISp) and three higher areas (VISrl, VISal VISlm) an awake mouse viewing natural movies synthetic stimuli. The data were co-registered volumetric electron microscopy (EM) reconstruction containing...
Objectives There is an unmet need for accurate and user-friendly definitions of systemic lupus erythematosus (SLE) disease activity remission. We aimed to derive validate the SLE Disease Activity Score (SLE-DAS) categories clinical remission state. Methods Derivation was conducted at Padova Lupus Clinic (Italy). Validation prospectively performed Cochin (France) by post hoc analysis BLISS-76 trial. At each clinic, expert classified patients in three categories: remission, mild or...
Abstract 3D electron microscopy (EM) has been successful at mapping invertebrate nervous systems, but the approach limited to small chunks of mammalian brains. To scale up larger volumes, we have built a computational pipeline for processing petascale image datasets acquired by serial section EM, popular form EM. The employs convolutional nets compute nonsmooth transformations required align images sections containing numerous cracks and folds, detect neuronal boundaries, label voxels as...
A primary cilium is a thin membrane-bound extension off cell surface that contains receptors for perceiving and transmitting signals modulate state activity. While many types have cilium, little known about cilia in the brain, where they are less accessible than on cultured cells or epithelial tissues protrude from bodies into deep, dense network of glial neuronal processes. Here, we investigated frequency, internal structure, shape, position large, high-resolution transmission electron...
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 new annotations correct errors the automated by proofreading. In large datasets, every proofreading edit relabels cell identities of millions voxels thousands like synapses. For analysis, require immediate reproducible...
Summary We present a semi-automated reconstruction of L2/3 mouse primary visual cortex from 3 million cubic microns electron microscopic images, including pyramidal and inhibitory neurons, astrocytes, microglia, oligodendrocytes precursors, pericytes, vasculature, mitochondria, synapses. Visual responses subset cells are included. The data being made publicly available, along with tools for programmatic 3D interactive access. density synaptic inputs onto neurons varies across cell classes...
Abstract The activity and connectivity of inhibitory cells has a profound impact on the operation neuronal networks. While average many cell types been characterized, we still lack an understanding how individual interneurons distribute their synapses onto targets heterogeneous inhibition is different excitatory neurons. Here, use large-scale volumetric electron microscopy (EM) functional imaging to address this question for chandelier in layer 2/3 mouse visual cortex. Using dense...
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...
The complexity of neural circuits makes it challenging to decipher the brain’s algorithms intelligence. Recent break-throughs in deep learning have produced models that accurately simulate brain activity, enhancing our understanding computational objectives and coding. However, these struggle generalize beyond their training distribution, limiting utility. emergence foundation models, trained on vast datasets, has introduced a new AI paradigm with remarkable generalization capabilities. We...
A primary cilium is a membrane-bound extension from the cell surface that contains receptors for perceiving and transmitting signals modulate state activity. Primary cilia in brain are less accessible than on cultured cells or epithelial tissues because they protrude into deep, dense network of glial neuronal processes. Here, we investigated frequency, internal structure, shape, position large, high-resolution transmission electron microscopy volumes mouse visual cortex. Cilia extended...
Maps of the nervous system that identify individual cells along with their type, subcellular components and connectivity have potential to elucidate fundamental organizational principles neural circuits. Nanometer-resolution imaging brain tissue provides necessary raw data, but inferring cellular annotation layers is challenging. We present segmentation-guided contrastive learning representations (SegCLR), a self-supervised machine technique produces directly from 3D imagery segmentations....
We are now in the era of millimeter-scale electron microscopy (EM) volumes collected at nanometer resolution (Shapson-Coe et al., 2021; Consortium 2021). Dense reconstruction cellular compartments these EM has been enabled by recent advances Machine Learning (ML) (Lee 2017; Wu Lu Macrina Automated segmentation methods produce exceptionally accurate reconstructions cells, but post-hoc proofreading is still required to generate large connectomes free merge and split errors. The elaborate 3-D...