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Namiki, S.

Publications and source records attributed to Namiki, S..

15 recordsLinked to original sources

An updated catalogue of split-GAL4 driver lines for descending neurons in Drosophila melanogaster

Descending neurons (DNs) occupy a key position in the sensorimotor hierarchy, conveying signals from the brain to the rest of the body below the neck. In Drosophila melanogaster flies, approximately 480 DN cell types have been described from electron-microscopy image datasets. Genetic access to these cell types is crucial for further investigation of their role in generating behaviour. We previously conducted the first large-scale survey of Drosophila melanogaster DNs, describing 98 unique cell types from light microscopy and generating cell-type-specific split-Gal4 driver lines for 65 of them. Here, we extend our previous work, describing the morphology of 146 additional DN types from light microscopy, bringing the total number DN types identified in light microscopy datasets to 244, or roughly 50% of all DN types. In addition, we produced 500 new sparse split-Gal4 driver lines and compiled a list of previously published DN lines from the literature for a combined list of 806 split-Gal4 driver lines targeting 190 DN types.

neuroscience↗

Adaptive decision-making by ants in response to past, imminent, and predicted adversity

Many animals exhibit innate behaviours, which are often interpreted as hard-wired, reflex-like responses, particularly in insects. Among these behaviours, beacon-aiming--an approach towards dark areas or objects--is observed in many animals; however, its functional significance remains unclear, and some ant species do not exhibit it. Here we show that in one such species, Camponotus japonicus, the behaviour was triggered only under adverse substrate conditions, such as during the crossing of liquid-covered surfaces, regardless of the locomotor patterns like walking or swimming, or the mere presence of water, or when walking upside-down. Once initiated, beacon-aiming persists even under normal substrate conditions, as demonstrated by ants transitioning from water-covered to dry substrates suitable for comfortable walking. This behavioural flexibility indicates that the innate behaviour is not hard-wired but modulated by internal states. Furthermore, changes in internal states may serve adaptive decision-making, potentially allowing ants to prepare for future adverse conditions. The isolated ants on a water-surrounded platform gradually established an attraction to the direction of the beacon before ultimately swimming towards it. These findings suggest that beacon-aiming is regulated by internal states, especially anxiety-like states formed in response to past, imminent, and predicted adverse substrate conditions in ants.

animal behavior and cognition↗

Comparative connectomics of the descending and ascending neurons of the Drosophila nervous system: stereotypy and sexual dimorphism

In most complex nervous systems there is a clear anatomical separation between the nerve cord, which contains most of the final motor outputs necessary for behaviour, and the brain. In insects, the neck connective is both a physical and information bottleneck connecting the brain and the ventral nerve cord (VNC, spinal cord analogue) and comprises diverse populations of descending (DN), ascending (AN) and sensory ascending neurons, which are crucial for sensorimotor signalling and control. Integrating three separate EM datasets, we now provide a complete connectomic description of the ascending and descending neurons of the female nervous system of Drosophila and compare them with neurons of the male nerve cord. Proofread neuronal reconstructions have been matched across hemispheres, datasets and sexes. Crucially, we have also matched 51% of DN cell types to light level data defining specific driver lines as well as classifying all ascending populations. We use these results to reveal the general architecture, tracts, neuropil innervation and connectivity of neck connective neurons. We observe connected chains of descending and ascending neurons spanning the neck, which may subserve motor sequences. We provide a complete description of sexually dimorphic DN and AN populations, with detailed analysis of circuits implicated in sex-related behaviours, including female ovipositor extrusion (DNp13), male courtship (DNa12/aSP22) and song production (AN hemilineage 08B). Our work represents the first EM-level circuit analyses spanning the entire central nervous system of an adult animal.

neuroscience↗

Transforming descending input into behavior: The organization of premotor circuits in the Drosophila Male Adult Nerve Cord connectome

In most animals, a relatively small number of descending neurons (DNs) connect higher brain centers in the animals head to circuits and motor neurons (MNs) in the nerve cord of the animals body that effect movement of the limbs. To understand how brain signals generate behavior, it is critical to understand how these descending pathways are organized onto the body MNs. In the fly, Drosophila melanogaster, MNs controlling muscles in the leg, wing, and other motor systems reside in a ventral nerve cord (VNC), analogous to the mammalian spinal cord. In companion papers, we introduced a densely-reconstructed connectome of the Drosophila Male Adult Nerve Cord (MANC, (Takemura et al., 2024)), including cell type and developmental lineage annotation (Marin et al., 2024), which provides complete VNC connectivity at synaptic resolution. Here, we present a first look at the organization of the VNC networks connecting DNs to MNs based on this new connectome information. We proofread and curated all DNs and MNs to ensure accuracy and reliability, then systematically matched DN axon terminals and MN dendrites with light microscopy data to link their VNC morphology with their brain inputs or muscle targets. We report both broad organizational patterns of the entire network and fine-scale analysis of selected circuits of interest. We discover that direct DN-MN connections are infrequent and identify communities of intrinsic neurons linked to control of different motor systems, including putative ventral circuits for walking, dorsal circuits for flight steering and power generation, and intermediate circuits in the lower tectulum for coordinated action of wings and legs. Our analysis generates hypotheses for future functional experiments and, together with the MANC connectome, empowers others to investigate these and other circuits of the Drosophila ventral nerve cord in richer mechanistic detail.

neuroscience↗

Single-cell type analysis of wing premotor circuits in the ventral nerve cord of Drosophila melanogaster

To perform most behaviors, animals must send commands from higher-order processing centers in the brain to premotor circuits that reside in ganglia distinct from the brain, such as the mammalian spinal cord or insect ventral nerve cord. How these circuits are functionally organized to generate the great diversity of animal behavior remains unclear. An important first step in unraveling the organization of premotor circuits is to identify their constituent cell types and create tools to monitor and manipulate these with high specificity to assess their functions. This is possible in the tractable ventral nerve cord of the fly. To generate such a toolkit, we used a combinatorial genetic technique (split-GAL4) to create 195 sparse transgenic driver lines targeting 196 individual cell types in the ventral nerve cord. These included wing and haltere motoneurons, modulatory neurons, and interneurons. Using a combination of behavioral, developmental, and anatomical analyses, we systematically characterized the cell types targeted in our collection. In addition, we identified correspondences between the cells in this collection and a recent connectomic data set of the ventral nerve cord. Taken together, the resources and results presented here form a powerful toolkit for future investigations of neuronal circuits and connectivity of premotor circuits while linking them to behavioral outputs.

neuroscience↗

High performance, large-scale multi-compartment Hodgkin-Huxley simulation of Drosophila's whole-brain neural circuit model

A major challenge in neurosciences is the elucidation of neural mechanisms in brains that are crucial for the processing of sensory information and the generation of adaptive behavior. In conjunction with the ever-growing body of experimental data, computational simulations have become crucial in integrating information and testing hypotheses, requiring fast large-scale simulators. We constructed a whole-brain neural circuit model of the fly Drosophila with biophysically detailed multi-compartment Hodgkin-Huxley models based on the morphologies of individual neurons published in open databases. Performance tuning of the simulator enabled near real-time simulation of the resting state of the Drosophila whole-brain model in the large-scale computational environment of the supercomputer Fugaku, for which we achieved in excess of 630 TFLOPS using 480k cores. In our whole-brain model, neural circuit dynamics related to a standard insect learning paradigm, the association of taste rewards with odors could be simulated.

neuroscience↗

Synapse type-specific molecular nanoconfigurations of the presynaptic active zone in the hippocampus identified by systematic nanoscopy

Neurotransmitters are released by exocytosis from synaptic vesicles at the active zone in the presynaptic terminal. The scaffold of the active zone consists of only a few evolutionarily conserved proteins, including RIM, CAST/ELKS, and RIM-BP, and tethers Munc13 and Ca2+ channels. The molecular principles that enable these proteins to mediate synaptic diversity have remained unclear. Here, we identified synapse type-specific molecular nanoconfigurations in the active zone by systematic quantification of active zone proteins using nanoscopy at two types of excitatory synapses and two types of inhibitory synapses in the rat hippocampal CA3 region. Quantitative analysis revealed that Munc13 content was particularly varied among the various synapse types and that the physical proximity of Ca2+ channels to the active zone scaffolds correlated with the efficacy of neurotransmitter release. We propose that the active zone is a flexible supramolecular assembly that can tune its composition and spatial configuration to adjust neurotransmitter release.

neuroscience↗

A population of descending neurons that regulate the flight motor of Drosophila

Like many insect species, Drosophila melanogaster are capable of maintaining a stable flight trajectory for periods lasting up to several hours(1, 2). Because aerodynamic torque is roughly proportional to the fifth power of wing length(3), even small asymmetries in wing size require the maintenance of subtle bilateral differences in flapping motion to maintain a stable path. Flies can even fly straight after losing half of a wing, a feat they accomplish via very large, sustained kinematic changes to the both damaged and intact wings(4). Thus, the neural network responsible for stable flight must be capable of sustaining fine-scaled control over wing motion across a large dynamic range. In this paper, we describe an unusual type of descending neurons (DNg02) that project directly from visual output regions of the brain to the dorsal flight neuropil of the ventral nerve cord. Unlike most descending neurons, which exist as single bilateral pairs with unique morphology, there is a population of at least 15 DNg02 cell pairs with nearly identical shape. By optogenetically activating different numbers of DNg02 cells, we demonstrate that these neurons regulate wingbeat amplitude over a wide dynamic range via a population code. Using 2-photon functional imaging, we show that DNg02 cells are responsive to visual motion during flight in a manner that would make them well suited to continuously regulate bilateral changes in wing kinematics. Collectively, we have identified a critical set of DNs that provide the sensitivity and dynamic range required for flight control.

neuroscience↗

Quantitative modeling of regular retinal microglia distribution

1Microglia are resident immune cells in the central nervous system (CNS), showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglias morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell-cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia. Author summaryMicroglia are resident immune cells in the central nervous system. It is known that the microglia cells show a regular distribution, but the mechanism underlying the regular distribution remains to be elucidated. In the present study, we quantitatively assayed the regularity of the microglia soma distribution using the image processing technique. Next, we formulated a mathematical model of cell distribution that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters using organ culture. As a result, we obtained parameters for cell migration, cell process dynamics, and extracellular ATP dynamics. Then we undertook numerical simulation of the mathematical model using the parameters obtained by the experiments. The resulting model simulations showed that direct cell-cell contact is the most important factor in generating regular spacing. Finally, we screened possible molecular pathways involved in the regular spacing of microglia, which confirmed the validity of the model.

cell biology↗

An image resource of subdivided Drosophila GAL4-driver expression patterns for neuron-level searches

Precise, repeatable genetic access to specific neurons via GAL4/UAS and related methods is a key advantage of Drosophila neuroscience. Neuronal targeting is typically documented using light microscopy of full GAL4 expression patterns, which generally lack the single-cell resolution required for reliable cell type identification. Here we use stochastic GAL4 labeling with the MultiColor FlpOut approach to generate cellular resolution confocal images at large scale. We are releasing aligned images of 74,000 such adult central nervous systems. An anticipated use of this resource is to bridge the gap between neurons identified by electron or light microscopy. Identifying individual neurons that make up each GAL4 expression pattern improves the prediction of split-GAL4 combinations targeting particular neurons. To this end we have made the images searchable on the NeuronBridge website. We demonstrate the potential of NeuronBridge to rapidly and effectively identify neuron matches based on morphology across imaging modalities and datasets.

neuroscience↗

Descending pathways from the lateral accessory lobe and posterior slope in the brain of the silkmoth Bombyx mori

A population of descending neurons connect the brain and thoracic motor center, playing a critical role in controlling behavior. We examined the anatomical organization of descending neurons (DNs) in the brain of the silkmoth Bombyx mori. Moth pheromone orientation is a good model to investigate the neuronal mechanisms of olfactory behavior. Based on mass staining and single-cell staining, we evaluated the anatomical organization of neurite distribution by DNs in the brain. Dense innervation was observed in the posterior ventral part of the brain, called the posterior slope (PS). We examined the morphology of DNs innervating the lateral accessory lobe (LAL), which is assumed to be important for moth olfactory behavior. We observed that the LAL DNs also innervate the PS, suggesting the integration of signals from the LAL and PS. We also identified a set of DNs innervating the PS, but not the LAL. These DNs were sensitive to sex pheromones, suggesting a role of the PS in motor control for pheromone orientation. The organization of descending pathways for pheromone orientation is discussed.

neuroscience↗

Speed dependent descending control of innate freezing behavior in Drosophila melanogaster

SummaryThe most fundamental choice an animal has to make when it detects a predator, or other threats, is whether to freeze, reducing its chances of being noticed, or to flee to safety. Here we show that Drosophila melanogaster exposed to looming stimuli in a confined arena either froze or fled. The probability of freezing versus fleeing was modulated by the flys walking speed at the time of threat, demonstrating that freeze/flee decisions were context dependent. We describe a pair of descending neurons crucially implicated in freezing. Genetic silencing of P9 descending neurons disrupted freezing yet did not prevent fleeing. Optogenetic activation of both P9 neurons induced running and freezing in a state-dependent manner. Our findings establish walking speed as a key factor in defensive response choices and reveal a pair of descending neurons as a critical component in the circuitry mediating selection and execution of freezing or fleeing behaviors.

neuroscience↗

The functional organization of descending sensory-motor pathways in Drosophila

In most animals, the brain controls the body via a set of descending neurons (DNs) that traverse the neck and terminate in post-cranial regions of the nervous system. This critical neural population is thought to activate, maintain and modulate locomotion and other behaviors. Although individual members of this cell class have been well-studied across species ranging from insects to primates, little is known about the overall connectivity pattern of DNs as a population. We undertook a systematic anatomical investigation of descending neurons in the fruit fly, Drosophila melanogaster, and created a collection of over 100 transgenic lines targeting individual cell types. Our methods allowed us to describe the morphology of roughly half of an estimated 400 DNs and create a comprehensive map of connectivity between the sensory neuropils in the brain and the motor neuropils in the ventral nerve cord. Like the vertebrate spinal cord, our results show that the fly nerve cord is a highly organized, layered system of neuropils, an organization that reflects the fact that insects are capable of two largely independent means of locomotion - walking and fight - using distinct sets of appendages. Our results reveal the basic functional map of descending pathways in flies and provide tools for systematic interrogation of sensory-motor circuits.

neuroscience↗

Optogenetic dissection of descending behavioral control in Drosophila

In most animals, the brain makes behavioral decisions that are transmitted by descending neurons to the nerve cord circuitry that produces behaviors. In insects, only a few descending neurons have been associated with specific behaviors. To explore how these neurons control an insects movements, we developed a novel method to systematically assay the behavioral effects of activating individual neurons on freely behaving terrestrial D. melanogaster. We calculated a two-dimensional representation of the entire behavior space explored by these flies and associated descending neurons with specific behaviors by identifying regions of this space that were visited with increased frequency during optogenetic activation. Applying this approach across a population of descending neurons, we found, that (1) activation of most of the descending neurons drove stereotyped behaviors, (2) in many cases multiple descending neurons activated similar behaviors, and (3) optogenetically-activated behaviors were often dependent on the behavioral state prior to activation.

neuroscience↗

A Systematic Nomenclature for the Drosophila Ventral Nervous System

The fruit fly, Drosophila melanogaster, is an established and powerful model system for neuroscience research with wide relevance in biology and medicine. Until recently, research on the Drosophila brain was hindered by the lack of a complete and uniform nomenclature. Recognising this problem, the Insect Brain Name Working Group produced an authoritative hierarchical nomenclature system for the adult insect brain, using Drosophila melanogaster as the reference framework, with other taxa considered to ensure greater consistency and expandability (Ito et al., 2014). Here, we extend this nomenclature system to the sub-gnathal regions of the adult Drosophila nervous system, thus providing a systematic anatomical description of the ventral nervous system (VNS). This portion of the nervous system includes the thoracic and abdominal neuromeres that were not included in the original work and contains the motor circuits that play essential roles in most fly behaviours.

neuroscience↗