@article {69008, title = {Nested neural circuits generate distinct acoustic signals during Drosophila courtship}, journal = {Current Biology}, volume = {34}, year = {2024}, month = {2024 Feb 26}, pages = {808-24}, abstract = {

Many motor control systems generate multiple movements using a common set of muscles. How are premotor circuits able to flexibly generate diverse movement patterns? Here, we characterize the neuronal circuits that drive the distinct courtship songs of\ Drosophila melanogaster. Male flies vibrate their wings towards females to produce two different song modes {\textendash} pulse and sine song {\textendash} which signal species identity and male quality. Using cell-type specific genetic reagents and the connectome, we provide a cellular and synaptic map of the circuits in the male ventral nerve cord that generate these songs and examine how activating or inhibiting each cell type within these circuits affects the song. Our data reveal that the song circuit is organized into two nested feed-forward pathways, with extensive reciprocal and feed-back connections. The larger network produces pulse song, the more complex and ancestral song form. A subset of this network produces sine song, the simpler and more recent form. Such nested organization may be a common feature of motor control circuits in which evolution has layered increasing flexibility on to a basic movement pattern.

}, doi = {10.1016/j.cub.2024.01.015}, url = {https://doi.org/10.1016/j.cub.2024.01.015}, author = {Joshua L. Lillvis and Kaiyu Wang and Hiroshi M. Shiozaki and Min Xu and David L. Stern and Barry J. Dickson} } @article {67907, title = {Ascending neurons convey behavioral state to integrative sensory and action selection centers in the brain}, journal = {Nature Neuroscience}, year = {2023}, month = {2023 Mar 31}, abstract = {

Knowledge of one{\textquoteright}s own behavioral state{\textemdash}whether one is walking, grooming, or resting{\textemdash}is critical for contextualizing sensory cues including interpreting visual motion and tracking odor sources. Additionally, awareness of one{\textquoteright}s own posture is important to avoid initiating destabilizing or physically impossible actions. Ascending neurons (ANs), interneurons in the vertebrate spinal cord or insect ventral nerve cord (VNC) that project to the brain, may provide such high-fidelity behavioral state signals. However, little is known about what ANs encode and where they convey signals in any brain. To address this gap, we performed a large-scale functional screen of AN movement encoding, brain targeting, and motor system patterning in the adult fly,\ Drosophila melanogaster. Using a new library of AN sparse driver lines, we measured the functional properties of 247 genetically-identifiable ANs by performing two-photon microscopy recordings of neural activity in tethered, behaving flies. Quantitative, deep network-based neural and behavioral analyses revealed that ANs nearly exclusively encode high-level behaviors{\textemdash}primarily walking as well as resting and grooming{\textemdash}rather than low-level joint or limb movements. ANs that convey self-motion{\textemdash}resting, walking, and responses to gust-like puff stimuli{\textemdash}project to the brain{\textquoteright}s anterior ventrolateral protocerebrum (AVLP), a multimodal, integrative sensory hub, while those that encode discrete actions{\textemdash}eye grooming, turning, and proboscis extension{\textemdash}project to the brain{\textquoteright}s gnathal ganglion (GNG), a locus for action selection. The structure and polarity of AN projections within the VNC are predictive of their functional encoding and imply that ANs participate in motor computations while also relaying state signals to the brain. Illustrative of this are ANs that temporally integrate proboscis extensions over tens-of-seconds, likely through recurrent interconnectivity. Thus, in line with long-held theoretical predictions, ascending populations convey high-level behavioral state signals almost exclusively to brain regions implicated in sensory feature contextualization and action selection.

}, doi = {10.1038/s41593-023-01281-z}, author = {Chin-Lin Chen and Florian Aymanns and Ryo Minegishi and Victor D. V. Matsuda and Nicolas Talabot and Semih G{\"u}nel and Barry J. Dickson and Pavan Ramdya} } @article {68974, title = {Combinatorial circuit dynamics orchestrate flexible motor patterns in Drosophila.}, journal = {bioRxiv}, year = {2023}, month = {2023 Sep 07}, abstract = {

Motor systems flexibly implement diverse motor programs to pattern behavioral sequences, yet their neural underpinnings remain unclear. Here, we investigated the neural circuit mechanisms of flexible courtship behavior in\ Drosophila. Courting males alternately produce two types of courtship song. By recording calcium signals in the ventral nerve cord (VNC) in behaving flies, we found that different songs are produced by activating overlapping neural populations with distinct motor functions in a combinatorial manner. Recordings from the brain suggest that song is driven by two descending pathways {\textendash} one defines when to sing and the other specifies what song to sing. Connectomic analysis reveals that these {\textquotedblleft}when{\textquotedblright} and {\textquotedblleft}what{\textquotedblright} descending pathways provide structured input to VNC neurons with different motor functions. These results suggest that dynamic changes in the activation patterns of descending pathways drive different combinations of motor modules, thereby flexibly switching between different motor actions.

}, doi = {10.1101/2022.12.14.520499}, url = {https://doi.org/10.1101/2022.12.14.520499}, author = {Hiroshi M. Shiozaki and Kaiyu Wang and Joshua L. Lillvis and Min Xu and Barry J. Dickson and David L. Stern} } @article {68966, title = {The Neural Basis of Drosophila Courtship Song}, journal = {bioRxiv}, year = {2023}, month = {2023 Sep 01}, abstract = {

Animal sounds are produced by patterned vibrations of specific organs, but the neural circuits that drive these vibrations are not well defined in any animal. Here we provide a functional and synaptic map of most of the neurons in the\ Drosophila\ male ventral nerve cord (the analog of the vertebrate spinal cord) that drive complex, patterned song during courtship. Male\ Drosophila\ vibrate their wings toward females during courtship to produce two distinct song modes {\textendash} pulse and sine song {\textendash} with characteristic features that signal species identity and male quality. We identified song-producing neural circuits by optogenetically activating and inhibiting identified cell types in the ventral nerve cord (VNC) and by tracing their patterns of synaptic connectivity in the male VNC connectome. The core song circuit consists of at least eight cell types organized into overlapping circuits, where all neurons are required for pulse song and a subset are required for sine song. The pulse and sine circuits each include a feed-forward pathway from brain descending neurons to wing motor neurons, with extensive reciprocal and feed-back connections. We also identify specific neurons that shape the individual features of each song mode. These results reveal commonalities amongst diverse animals in the neural mechanisms that generate diverse motor patterns from a single set of muscles.

}, doi = {10.1101/2023.08.30.555537}, url = {https://doi.org/10.1101/2023.08.30.555537}, author = {Joshua L. Lillvis and Kaiyu Wang and Hiroshi M. Shiozaki and Min Xu and David L. Stern and Barry J. Dickson} } @article {68569, title = {Neural coding of distinct motor patterns during Drosophila courtship song}, journal = {bioRxiv}, year = {2022}, month = {2022 Dec 15}, abstract = {

Animals flexibly switch between different actions by changing neural activity patterns for motor control. Courting\ Drosophila melanogaster\ males produce two different acoustic signals, pulse and sine song, each of which can be promoted by artificial activation of distinct neurons. However, how the activity of these neurons implements flexible song production is unknown. Here, we developed an assay to record neuronal calcium signals in the ventral nerve cord, which contains the song motor circuit, in singing flies. We found that sine-promoting neurons, but not pulse-promoting neurons, show strong activation during sine song. In contrast, both pulse- and sine-promoting neurons are active during pulse song. Furthermore, population calcium imaging in the song circuit suggests that sine song involves activation of a subset of neurons that are also active during pulse song. Thus, differential activation of overlapping, rather than distinct, neural populations underlies flexible motor actions during acoustic communication in\ D. melanogaster.

}, doi = {10.1101/2022.12.14.520499}, url = {https://doi.org/10.1101/2022.12.14.520499}, author = {Hiroshi M. Shiozaki and Kaiyu Wang and Joshua L. Lillvis and Min Xu and Barry J. Dickson and David L. Stern} } @article {67849, title = {Rapid reconstruction of neural circuits using tissue expansion and lattice light sheet microscopy}, journal = {eLife}, year = {2022}, month = {2022 Oct 26}, abstract = {

Electron microscopy (EM) allows for the reconstruction of dense neuronal connectomes but suffers from low throughput, limiting its application to small numbers of reference specimens. We developed a protocol and analysis pipeline using tissue expansion and lattice light-sheet microscopy (ExLLSM) to rapidly reconstruct selected circuits across many samples with single synapse resolution and molecular contrast. We validate this approach in\ Drosophila, demonstrating that it yields synaptic counts similar to those obtained by EM, can be used to compare counts across sex and experience, and to correlate structural connectivity with functional connectivity. This approach fills a critical methodological gap in studying variability in the structure and function of neural circuits across individuals within and between species.

}, doi = {10.7554/eLife.81248}, url = {https://doi.org/10.7554/eLife.81248}, author = {Joshua L. Lillvis and Hideo Otsuna and Xiaoyu Ding and Igor Pisarev and Takashi Kawase and Jennifer Colonell and Konrad Rokicki and Cristian Goina and Ruixuan Gao and Amy Hu and Kaiyu Wang and John Bogovic and Daniel E. Milkie and Edward S. Boyden and Stephan Saalfeld and Paul W. Tillberg and Barry J. Dickson} } @article {67948, title = {Taste quality interactions and transformations in a sensorimotor circuit}, journal = {eLife}, year = {2022}, month = {2022 Jul 06}, abstract = {

Taste detection and hunger state dynamically regulate the decision to initiate feeding. To study how context-appropriate feeding decisions are generated, we combined synaptic resolution circuit reconstruction with targeted genetic access to specific neurons to elucidate a gustatory sensorimotor circuit for feeding initiation in\ Drosophila melanogaster. This circuit connects gustatory sensory neurons to proboscis motor neurons through three intermediate layers. Most of the neurons in this pathway are necessary and sufficient for proboscis extension, a feeding initiation behavior, and respond selectively to sugar taste detection. Hunger signals act at select second-order neurons to increase feeding initiation in food-deprived animals. In contrast, a bitter taste pathway inhibits premotor neurons, illuminating a central mechanism that weighs sugar and bitter tastes to promote or inhibit feeding. Together, these studies reveal the neural circuit basis for the integration of external taste detection and internal nutritive state to flexibly execute a critical feeding decision.

}, doi = {10.1101/2022.03.06.483180}, url = {https://doi.org/10.1101/2022.03.06.483180}, author = {Philip K. Shiu and Gabriella R. Sterne and Stefanie Engert and Barry J. Dickson and Kristin Scott} }