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Abstract Sequenced behaviours, including locomotion, reaching and vocalization, are patterned differently in different contexts, enabling animals to adjust to their environments. How contextual information shapes neural activity to flexibly alter the patterning of actions is not fully understood. Previous work has indicated that this could be achieved via parallel motor circuits, with differing sensitivities to context^1,2. Here we demonstrate that a single pathway operates in two regimes dependent on recent sensory history. We leverage theDrosophilasong production system³to investigate the role of several neuron types^4–7in song patterning near versus far from the female fly. Male flies sing ‘simple’ trains of only one mode far from the female fly but complex song sequences comprising alternations between modes when near her. We find that ventral nerve cord (VNC) circuits are shaped by mutual inhibition and rebound excitability⁸between nodes driving the two song modes. Brief sensory input to a direct brain-to-VNC excitatory pathway drives simple song far from the female, whereas prolonged input enables complex song production via simultaneous recruitment of functional disinhibition of VNC circuitry. Thus, female proximity unlocks motor circuit dynamics in the correct context. We construct a compact circuit model to demonstrate that the identified mechanisms suffice to replicate natural song dynamics. These results highlight how canonical circuit motifs^8,9can be combined to enable circuit flexibility required for dynamic communication. 

Abstract The heterogeneity of brain imaging methods in neuroscience provides rich data that cannot be captured by a single technique, and our interpretations benefit from approaches that enable easy comparison both within and across different data types. For example, comparing brain-wide neural dynamics across experiments and aligning such data to anatomical resources, such as gene expression patterns or connectomes, requires precise alignment to a common set of anatomical coordinates. However, this is challenging because registeringin vivofunctional imaging data toex vivoreference atlases requires accommodating differences in imaging modality, microscope specification, and sample preparation. We overcome these challenges inDrosophilaby building anin vivoreference atlas from multiphoton-imaged brains, called the Functional Drosophila Atlas (FDA). We then develop a two-step pipeline, BrIdge For Registering Over Statistical Templates (BIFROST), for transforming neural imaging data into this common space and for importingex vivoresources such as connectomes. Using genetically labeled cell types as ground truth, we demonstrate registration with a precision of less than 10 microns. Overall, BIFROST provides a pipeline for registering functional imaging datasets in the fly, both within and across experiments. SignificanceLarge-scale functional imaging experiments inDrosophilahave given us new insights into neural activity in various sensory and behavioral contexts. However, precisely registering volumetric images from different studies has proven challenging, limiting quantitative comparisons of data across experiments. Here, we address this limitation by developing BIFROST, a registration pipeline robust to differences across experimental setups and datasets. We benchmark this pipeline by genetically labeling cell types in the fly brain and demonstrate sub-10 micron registration precision, both across specimens and across laboratories. We further demonstrate accurate registration betweenin-vivobrain volumes and ultrastructural connectomes, enabling direct structure-function comparisons in future experiments. 

Abstract 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 ofDrosophilaand 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. 

Abstract The fruit flyDrosophila melanogastercombines surprisingly sophisticated behaviour with a highly tractable nervous system. A large part of the fly’s success as a model organism in modern neuroscience stems from the concentration of collaboratively generated molecular genetic and digital resources. As presented in our FlyWire companion paper¹, this now includes the first full brain connectome of an adult animal. Here we report the systematic and hierarchical annotation of this ∼130,000-neuron connectome including neuronal classes, cell types and developmental units (hemilineages). This enables any researcher to navigate this huge dataset and find systems and neurons of interest, linked to the literature through the Virtual Fly Brain database². Crucially, this resource includes 4,552 cell types. 3,094 are rigorous consensus validations of cell types previously proposed in the “hemibrain” connectome³. In addition, we propose 1,458 new cell types, arising mostly from the fact that the FlyWire connectome spans the whole brain, whereas the hemibrain derives from a subvolume. Comparison of FlyWire and the hemibrain showed that cell type counts and strong connections were largely stable, but connection weights were surprisingly variable within and across animals. Further analysis defined simple heuristics for connectome interpretation: connections stronger than 10 unitary synapses or providing >1% of the input to a target cell are highly conserved. Some cell types showed increased variability across connectomes: the most common cell type in the mushroom body, required for learning and memory, is almost twice as numerous in FlyWire as the hemibrain. We find evidence for functional homeostasis through adjustments of the absolute amount of excitatory input while maintaining the excitation-inhibition ratio. Finally, and surprisingly, about one third of the cell types proposed in the hemibrain connectome could not yet be reliably identified in the FlyWire connectome. We therefore suggest that cell types should be defined to be robust to inter-individual variation, namely as groups of cells that are quantitatively more similar to cells in a different brain than to any other cell in the same brain. Joint analysis of the FlyWire and hemibrain connectomes demonstrates the viability and utility of this new definition. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open source toolchain for brain-scale comparative connectomics. 

Across the animal kingdom, social interactions rely on sound production and perception. From simple cricket chirps to more elaborate bird songs, animals go to great lengths to communicate information critical for reproduction and survival via acoustic signals. Insects produce a wide array of songs to attract a mate, and the intended receivers must differentiate these calls from competing sounds, analyze the quality of the sender from spectrotemporal signal properties, and then determine how to react. Insects use numerically simple nervous systems to analyze and respond to courtship songs, making them ideal model systems for uncovering the neural mechanisms underlying acoustic pattern recognition. We highlight here how the combination of behavioral studies and neural recordings in three groups of insects—crickets, grasshoppers, and fruit flies—reveals common strategies for extracting ethologically relevant information from acoustic patterns and how these findings might translate to other systems. 

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 to reconstruct local connectivity maps that are highly informative, yet inadequate for understanding brain function more globally. Here, we present the first neuronal wiring diagram of a whole adult brain, containing 5×10⁷chemical synapses between ∼130,000 neurons reconstructed from a femaleDrosophila melanogaster. The resource also incorporates annotations of cell classes and types, nerves, hemilineages, and predictions of neurotransmitter identities. Data products are available by download, programmatic access, and interactive browsing and made interoperable with other fly data resources. We show how to derive a projectome, a map of projections between regions, from the connectome. We demonstrate the tracing of synaptic pathways and the analysis of information flow from inputs (sensory and ascending neurons) to outputs (motor, endocrine, and descending neurons), across both hemispheres, and between the central brain and the optic lobes. Tracing from a subset of photoreceptors all the way to descending motor pathways illustrates how structure can uncover putative circuit mechanisms underlying sensorimotor behaviors. The technologies and open ecosystem of the FlyWire Consortium set the stage for future large-scale connectome projects in other species.