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Takemura, S.-y.

Publications and source records attributed to Takemura, S.-y..

10 recordsLinked to original sources

Sexual dimorphism in the complete connectome of the Drosophila male central nervous system

Sex differences in behaviour exist across all animals, typically under strong genetic regulation. In Drosophila, fruitless/doublesex transcription factors can identify dimorphic neurons but their organisation into functional circuits remains unclear. We present the connectome of the entire Drosophila male central nervous system. This contains 166,691 neurons spanning the brain and nerve cord, fully proofread and annotated including fruitless/doublesex expression and 11,691 types. We provide the first comprehensive comparison between male and female brain connectomes to synaptic resolution, finding 7,205 isomorphic, 114 dimorphic, 262 male-specific and 69 female-specific types. This resource enables analysis of full sensory-to-motor circuits underlying complex behaviours and the impact of dimorphic elements. Sex-specific/dimorphic neurons are concentrated in higher brain centres while the sensory and motor periphery are largely isomorphic. Within higher centres, male-specific connections are organised into hotspots defined by male-specific neurons or arbours. Numerous circuit switches reroute sensory information to form antagonistic circuits controlling opposing behaviours.

neuroscience↗

Connectome-driven neural inventory of a complete visual system

Vision provides animals with detailed information about their surroundings, conveying diverse features such as color, form, and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons, such that in animals as distant as flies and humans, visual regions comprise half the brains volume. These visual brain regions often reveal remarkable structure-function relationships, with neurons organized along spatial maps with shapes that directly relate to their roles in visual processing. To unravel the stunning diversity of a complex visual system, a careful mapping of the neural architecture matched to tools for targeted exploration of that circuitry is essential. Here, we report a new connectome of the right optic lobe from a male Drosophila central nervous system FIB-SEM volume and a comprehensive inventory of the flys visual neurons. We developed a computational framework to quantify the anatomy of visual neurons, establishing a basis for interpreting how their shapes relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity, and expert curation, we classified the [~]53,000 neurons into 727 types, about half of which are systematically described and named for the first time. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron type catalog. Together, this comprehensive set of tools and data unlock new possibilities for systematic investigations of vision in Drosophila, a foundation for a deeper understanding of sensory processing.

neuroscience↗

Systematic annotation of a complete adult male Drosophila nerve cord connectome reveals principles of functional organisation

Nervous systems function as ensembles of neurons communicating via synaptic connections, and a functional understanding of nervous systems requires extensive knowledge of their connectomes. In a companion paper (Takemura et al., 2023), we describe the acquisition of a complete fruit fly nerve cord connectome, the first for an animal that can walk or fly. Here, to efficiently navigate and to appreciate the biological significance of this connectome, we categorise and name nearly all neurons systematically and link them to the experimental literature. We employ a system of hierarchical coarse annotations and group similar neurons across the midline and across segments, then define systematic cell types for sensory neurons, intrinsic neurons, ascending neurons, and non-motor efferent neurons. Stereotyped arrays of neuroblasts generate related neuron populations called hemilineages that repeat across the segments of the nerve cord. We confirm that larval-born neurons from a given hemilineage generally express the same neurotransmitter but find that earlier born neurons often express a different one. We match over 35% of intrinsic, ascending, and non-motor efferent neurons across segments, defining serial sets which were crucial for systematic typing of motor neurons and sensory neurons. We assign a sensory modality to over 5000 sensory neurons, cluster them by connectivity, and identify serially homologous cell types and a layered organisation likely corresponding to peripheral topography. Finally, we present selected examples of sensory circuits predicated on programmatic analysis of a complete VNC connectome. Our annotations are critical for analysing the structure of descending input to the nerve cord and of motor output, both described in a third companion paper (Cheong et al., 2023). These annotations are being released as part of the neuprint.janelia.org and clio.janelia.org web applications and also serve as the basis for programmatic analysis of the connectome through dedicated tools that we describe in this paper.

neuroscience↗

A Connectome of the Male Drosophila Ventral Nerve Cord

Animal behavior is principally expressed through neural control of muscles. Therefore understanding how the brain controls behavior requires mapping neuronal circuits all the way to motor neurons. We have previously established technology to collect large-volume electron microscopy data sets of neural tissue and fully reconstruct the morphology of the neurons and their chemical synaptic connections throughout the volume. Using these tools we generated a dense wiring diagram, or connectome, for a large portion of the Drosophila central brain. However, in most animals, including the fly, the majority of motor neurons are located outside the brain in a neural center closer to the body, i.e. the mammalian spinal cord or insect ventral nerve cord (VNC). In this paper, we extend our effort to map full neural circuits for behavior by generating a connectome of the VNC of a male fly.

neuroscience↗

Connectome-constrained deep mechanistic networks predict neural responses across the fly visual system at single-neuron resolution

We can now measure the connectivity of every neuron in a neural circuit, but we are still blind to other biological details, including the dynamical characteristics of each neuron. The degree to which connectivity measurements alone can inform understanding of neural computation is an open question. Here we show that with only measurements of the connectivity of a biological neural network, we can predict the neural activity underlying neural computation. We constructed a model neural network with the experimentally determined connectivity for 64 cell types in the motion pathways of the fruit fly optic lobe but with unknown parameters for the single neuron and single synapse properties. We then optimized the values of these unknown parameters using techniques from deep learning, to allow the model network to detect visual motion. Our mechanistic model makes detailed experimentally testable predictions for each neuron in the connectome. We found that model predictions agreed with experimental measurements of neural activity across 24 studies. Our work demonstrates a strategy for generating detailed hypotheses about the mechanisms of neural circuit function from connectivity measurements. We show that this strategy is more likely to be successful when neurons are sparsely connected--a universally observed feature of biological neural networks across species and brain regions.

neuroscience↗

A connectome of the Drosophila central complex reveals network motifs suitable for flexible navigation and context-dependent action selection

Flexible behaviors over long timescales are thought to engage recurrent neural networks in deep brain regions, which are experimentally challenging to study. In insects, recurrent circuit dynamics in a brain region called the central complex (CX) enable directed locomotion, sleep, and context- and experience-dependent spatial navigation. We describe the first complete electron-microscopy-based connectome of the Drosophila CX, including all its neurons and circuits at synaptic resolution. We identified new CX neuron types, novel sensory and motor pathways, and network motifs that likely enable the CX to extract the flys head-direction, maintain it with attractor dynamics, and combine it with other sensorimotor information to perform vector-based navigational computations. We also identified numerous pathways that may facilitate the selection of CX-driven behavioral patterns by context and internal state. The CX connectome provides a comprehensive blueprint necessary for a detailed understanding of network dynamics underlying sleep, flexible navigation, and state-dependent action selection.

neuroscience↗

Isotropic 3D electron microscopy reference library of whole cells and tissues

Understanding cellular architecture is essential for understanding biology. Electron microscopy (EM) uniquely visualizes cellular structures with nanometer resolution. However, traditional methods, such as thin-section EM or EM tomography, have limitations inasmuch as they only visualize a single slice or a relatively small volume of the cell, respectively. Focused Ion Beam-Scanning Electron Microscopy (FIB-SEM) demonstrated the ability to image cellular samples at 4-nm isotropic voxels with rather limited imageable volume. Here, we present 3D EM images of whole cells and tissues with two orders of magnitude increases in imageable volume at 4-nm voxels. Such data with a combined fine resolution scale and large sample size do not currently exist, and are enabled by the advances in higher precision and stability of FIB milling, together with enhanced signal detection and faster SEM scanning. More importantly, we have generated a volume EM atlas encompassing ten diverse datasets of whole cells and tissues, from cancer cells to immune cells, and from mouse pancreatic islets to Drosophila neural tissues. These open-access data (via OpenOrganelle) represent a foundation to nucleate a new field of high-resolution whole-cell volume EM and subsequent analyses, and invite biologists to explore this new paradigm and pose fundamentally new questions.

cell biology↗

A Connectome and Analysis of the Adult Drosophila Central Brain

The neural circuits responsible for animal behavior remain largely unknown. We summarize new methods and present the circuitry of a large fraction of the brain of the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses in, and proofread such large data sets. We define cell types, refine computational compartments, and provide an exhaustive atlas of cell examples and types, many of them novel. We provide detailed circuits consisting of neurons and their chemical synapses for most of the central brain. We make the data public and simplify access, reducing the effort needed to answer circuit questions, and provide procedures linking the neurons defined by our analysis with genetic reagents. Biologically, we examine distributions of connection strengths, neural motifs on different scales, electrical consequences of compartmentalization, and evidence that maximizing packing density is an important criterion in the evolution of the flys brain.

bioinformatics↗

A Connectome of the Adult Drosophila Central Brain

The neural circuits responsible for behavior remain largely unknown. Previous efforts have reconstructed the complete circuits of small animals, with hundreds of neurons, and selected circuits for larger animals. Here we (the FlyEM project at Janelia and collaborators at Google) summarize new methods and present the complete circuitry of a large fraction of the brain of a much more complex animal, the fruit fly Drosophila melanogaster. Improved methods include new procedures to prepare, image, align, segment, find synapses, and proofread such large data sets; new methods that define cell types based on connectivity in addition to morphology; and new methods to simplify access to a large and evolving data set. From the resulting data we derive a better definition of computational compartments and their connections; an exhaustive atlas of cell examples and types, many of them novel; detailed circuits for most of the central brain; and exploration of the statistics and structure of different brain compartments, and the brain as a whole. We make the data public, with a web site and resources specifically designed to make it easy to explore, for all levels of expertise from the expert to the merely curious. The public availability of these data, and the simplified means to access it, dramatically reduces the effort needed to answer typical circuit questions, such as the identity of upstream and downstream neural partners, the circuitry of brain regions, and to link the neurons defined by our analysis with genetic reagents that can be used to study their functions. Note: In the next few weeks, we will release a series of papers with more involved discussions. One paper will detail the hemibrain reconstruction with more extensive analysis and interpretation made possible by this dense connectome. Another paper will explore the central complex, a brain region involved in navigation, motor control, and sleep. A final paper will present insights from the mushroom body, a center of multimodal associative learning in the fly brain.

neuroscience↗

Interactions with presynaptic photoreceptors mediated by the Dpr11 and DIP-γ cell surface proteins control selection and survival of Drosophila amacrine neurons

Drosophila R7 UV photoreceptors (PRs) are divided into yellow (y) and pale (p) subtypes with different wavelength sensitivities. yR7 PRs express the Dpr11 cell surface protein and are presynaptic to Dm8 amacrine neurons (yDm8) that express Dpr11s binding partner DIP-{gamma}, while pR7 PRs synapse onto DIP-{gamma}-negative pDm8 neurons. Dpr11 and DIP-{gamma} expression patterns define yellow and pale medulla color vision circuits that project to higher-order areas. DIP- {gamma} and dpr11 mutations affect the morphology of yDm8 arbors in the yellow circuit. yDm8 neurons are generated in excess during development and compete for presynaptic yR7 partners. Transsynaptic interactions between Dpr11 and DIP-{gamma} are required for generation of neurotrophic signals that allow yDm8 neurons to survive. yDm8 and pDm8 neurons do not normally compete for neurotrophic support, but can be forced to do so by manipulating R7 subtype fates. DIP-{gamma}-Dpr11 interactions allow yDm8 neurons to select yR7 PRs as their home column partners.

neuroscience↗