Thomas Macrina
A5021620351- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Neurobiology and Insect Physiology Research
- Advanced Electron Microscopy Techniques and Applications
- Cell Image Analysis Techniques
- Photoreceptor and optogenetics research
- Advanced Fluorescence Microscopy Techniques
- Physiological and biochemical adaptations
- Advanced Memory and Neural Computing
- Insect and Arachnid Ecology and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Scientific Computing and Data Management
- Electron and X-Ray Spectroscopy Techniques
- Domain Adaptation and Few-Shot Learning
- Advanced Image and Video Retrieval Techniques
- Bioinformatics and Genomic Networks
- Neurogenesis and neuroplasticity mechanisms
- Image Retrieval and Classification Techniques
- Retinal Development and Disorders
- Fossil Insects in Amber
- Advanced Neural Network Applications
- Animal Behavior and Reproduction
- Functional Brain Connectivity Studies
- Immune cells in cancer
- Medical Image Segmentation Techniques
Princeton University
2019-2024
Neuroscience Institute
2020-2024
Laboratoire d'Informatique de Paris-Nord
2020-2023
Abstract Connections between neurons can be mapped by acquiring and analyzing electron microscopic (EM) brain images. In recent years, this approach has been applied to chunks of brains reconstruct local connectivity maps that are highly informative, yet inadequate for understanding function more globally. Here, we present the first neuronal wiring diagram a whole adult brain, containing 5×10 7 chemical synapses ∼130,000 reconstructed from female Drosophila melanogaster . The resource also...
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...
Sustained changes in mood or action require persistent neural activity, but it has been difficult to identify the circuit mechanisms that underlie activity and contribute long-lasting behavior. Here, we show a subset of Doublesex+ pC1 neurons Drosophila female brain, called pC1d/e, can drive minutes-long behavior presence males. Using automated reconstruction volume electron microscopic (EM) image map all inputs outputs both pC1d pC1e. This reveals strong recurrent connectivity between,...
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...
Abstract The reconstruction of neural circuits from serial section electron microscopy (ssEM) images is being accelerated by automatic image segmentation methods. Segmentation accuracy often limited the preceding step aligning 2D to create a 3D stack. Precise and robust alignment in presence artifacts challenging, especially as datasets are attaining petascale. We present computational pipeline for ssEM with several key elements. Self-supervised convolutional nets trained via metric learning...
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...
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...
Animal movement is controlled by motor neurons (MNs), which project out of the central nervous system to activate muscles. MN activity coordinated complex premotor networks that allow individual muscles contribute many different behaviors. Here, we use connectomics analyze wiring logic circuits controlling
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...
ABSTRACT Due to advances in automated image acquisition and analysis, new whole-brain connectomes beyond C. elegans are finally on the horizon. Proofreading of reconstructions will require many person-years effort, due huge volumes data involved. Here we present FlyWire, an online community for proofreading neural circuits a fly brain, explain how its computational social structures organized scale up connectomics. Browser-based 3D interactive segmentation by collaborative editing spatially...
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...
Summary Like the vertebrate spinal cord, insect ventral nerve cord (VNC) mediates limb sensation and motor control. Here, we apply automated tools for electron microscopy volume alignment, neuron segmentation, synapse prediction toward creating a connectome of an adult female Drosophila VNC. To interpret connectome, it is crucial to know its relationship with rest body. We therefore mapped muscle targets leg wing neurons in by comparing their morphology genetic driver lines, dye fills, X-ray...
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...
Neural circuit function is shaped both by the cell types that comprise and connections between those 1 . have previously been defined morphology 2, 3 , electrophysiology 4, 5 transcriptomic expression 6-8 connectivity 9-13 or even a combination of such modalities 14-16 More recently, Patch-seq technique has enabled characterization (M), (E), (T) properties from individual cells 17-20 Using this technique, these were integrated to define 28, inhibitory multimodal, MET-types in mouse primary...