@article {69502, title = {Steering From the Rear: Coordination of Central Pattern Generators Underlying Navigation by Ascending Interneurons}, journal = {bioRxiv}, year = {2024}, month = {2024 Jun 17}, abstract = {

Understanding how animals coordinate movements to achieve goals is a fundamental pursuit in neuroscience. Here we explore how neurons that reside in posterior lower-order regions of a locomotor system and project to anterior higher-order regions influence steering and navigation. We characterized the anatomy and functional role of a population of ascending interneurons in the ventral nerve cord of Drosophila larvae. Through electron microscopy reconstructions and light microscopy, we determined that the cholinergic 19f cells receive input primarily from premotor interneurons and synapse upon a diverse array of postsynaptic targets within the anterior segments including other 19f cells. Calcium imaging of 19f activity in isolated CNS preparations in relation to motor neurons revealed that 19f neurons are recruited into most larval motor programmes. 19f activity lags behind motor neuron activity and as a population, the cells encode spatio-temporal patterns of locomotor activity in the larval CNS. Optogenetic manipulations of 19f cell activity in isolated CNS preparations revealed that they coordinate the activity of central pattern generators underlying exploratory headsweeps and forward locomotion in a context and location specific manner. In behaving animals, activating 19f cells suppressed exploratory headsweeps and slowed forward locomotion, while inhibition of 19f activity potentiated headsweeps, slowing forward movement. Inhibiting activity in 19f cells ultimately affected the ability of larvae to remain in the vicinity of an odor source during an olfactory navigation task. Overall, our findings provide insights into how ascending interneurons monitor motor activity and shape interactions amongst rhythm generators underlying complex navigational tasks.

}, doi = {10.1101/2024.06.17.598162}, url = {https://www.biorxiv.org/content/early/2024/06/17/2024.06.17.598162}, author = {Jonaitis, Julius and Hibbard, Karen L and Layte, Kaity McCafferty and Hiramoto, Atsuki and Cardona, Albert and Truman, James W and Nose, Akinao and Zwart, Maarten F and Pulver, Stefan R} } @article {64988, title = {Regulation of forward and backward locomotion through intersegmental feedback circuits in Drosophila larvae.}, journal = {Nature Communications}, volume = {10}, year = {2019}, month = {2019 Jun 14}, pages = {2654}, abstract = {

Animal locomotion requires spatiotemporally coordinated contraction of muscles throughout the body. Here, we investigate how contractions of antagonistic groups of muscles are intersegmentally coordinated during bidirectional crawling of Drosophila larvae. We identify two pairs of higher-order premotor excitatory interneurons present in each abdominal neuromere that intersegmentally provide feedback to the adjacent neuromere during motor propagation. The two feedback neuron pairs are differentially active during either forward or backward locomotion but commonly target a group of premotor interneurons that together provide excitatory inputs to transverse muscles and inhibitory inputs to the antagonistic longitudinal muscles. Inhibition of either feedback neuron pair compromises contraction of transverse muscles in a direction-specific manner. Our results suggest that the intersegmental feedback neurons coordinate contraction of synergistic muscles by acting as delay circuits representing the phase lag between segments. The identified circuit architecture also shows how bidirectional motor networks could be economically embedded in the nervous system.

}, issn = {2041-1723}, doi = {10.1038/s41467-019-10695-y}, author = {Kohsaka, Hiroshi and Zwart, Maarten F and Fushiki, Akira and Fetter, Richard D and Truman, James W and Cardona, Albert and Nose, Akinao} } @article {48941, title = {Reactive oxygen species regulate activity-dependent neuronal structural plasticity in Drosophila.}, journal = {eLife}, year = {2018}, month = {2018 Dec 12}, abstract = {

Neurons are inherently plastic, adjusting their structure, connectivity and excitability in response to changes in activity. How neurons sense changes in their activity level and then transduce these to structural changes remains to be fully elucidated. Working with the Drosophila larval locomotor network, we show that neurons use reactive oxygen species (ROS), metabolic byproducts, to monitor their activity. ROS signals are both necessary and sufficient for activity-dependent structural adjustments of both pre- and postsynaptic terminals and for network output, as measured by larval crawling behavior. We find the highly conserved Parkinsons disease-linked protein DJ-1b acts as a redox sensor in neurons where it regulates pre- and postsynaptic structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. Neuronal ROS thus play an important physiological role as second messengers required for neuronal and network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.

}, doi = {10.7554/eLife.39393}, author = {Oswald, Matthew C W and Brooks, Paul S and Zwart, Maarten F and Mukherjee, Amrita and West, Ryan J H and Morarach, Khomgrit and Sweeney, Sean T and Landgraf, Matthias} } @article {47324, title = {A circuit mechanism for the propagation of waves of muscle contraction in Drosophila.}, journal = {eLife}, volume = {5}, year = {2016}, month = {2016 Feb 18}, abstract = {

Animals move by adaptively coordinating the sequential activation of muscles. The circuit mechanisms underlying coordinated locomotion are poorly understood. Here, we report on a novel circuit for propagation of waves of muscle contraction, using the peristaltic locomotion of Drosophila larvae as a model system. We found an intersegmental chain of synaptically connected neurons, alternating excitatory and inhibitory, necessary for wave propagation and active in phase with the wave. The excitatory neurons (A27h) are premotor and necessary only for forward locomotion, and are modulated by stretch receptors and descending inputs. The inhibitory neurons (GDL) are necessary for both forward and backward locomotion, suggestive of different yet coupled central pattern generators, and its inhibition is necessary for wave propagation. The circuit structure and functional imaging indicated that the commands to contract one segment promote the relaxation of the next segment, revealing a mechanism for wave propagation in peristaltic locomotion.

}, issn = {2050-084X}, doi = {10.7554/eLife.13253}, author = {Fushiki, Akira and Zwart, Maarten F and Kohsaka, Hiroshi and Fetter, Richard D and Cardona, Albert and Nose, Akinao} } @article {47698, title = {Selective inhibition mediates the sequential recruitment of motor pools.}, journal = {Neuron}, volume = {91}, year = {2016}, month = {2016 Jul 12}, pages = {615-28}, abstract = {

Locomotor systems generate diverse motor patterns to produce the movements underlying behavior, requiring that motor neurons be recruited at various phases of the locomotor cycle. Reciprocal inhibition produces alternating motor patterns; however, the mechanisms that generate other phasic relationships between intrasegmental motor pools are unknown. Here, we investigate one such motor pattern in the Drosophila larva, using a multidisciplinary approach including electrophysiology and ssTEM-based circuit reconstruction. We find that two motor pools that are sequentially recruited during locomotion have identical excitable properties. In contrast, they receive input from divergent premotor circuits. We find that this motor pattern is not orchestrated by differential excitatory input but by a GABAergic interneuron acting as a delay line to the later-recruited motor pool. Our findings show how a motor pattern is generated as a function of the modular organization of locomotor networks through segregation of\ inhibition, a potentially general mechanism for sequential motor patterns.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2016.06.031}, author = {Zwart, Maarten F and Pulver, Stefan R and Truman, James W and Fushiki, Akira and Cardona, Albert and Landgraf, Matthias} } @article {47991, title = {The serotonergic system tracks the outcomes of actions to mediate short-term motor learning.}, journal = {Cell}, volume = {167}, year = {2016}, month = {2016 Oct 27}, pages = {933-46}, abstract = {

To execute accurate movements, animals must continuously adapt their behavior to changes in their\ bodies and environments. Animals can learn changes in the relationship between their locomotor commands and the resulting distance moved, then adjust command strength to achieve a desired travel distance. It is largely unknown which circuits implement this form of motor learning, or how. Using whole-brain neuronal imaging and circuit manipulations in larval zebrafish, we discovered that the serotonergic dorsal raphe nucleus (DRN) mediates short-term locomotor learning. Serotonergic DRN neurons respond phasically to swim-induced visual motion, but little to motion that is not self-generated. During prolonged exposure to a given motosensory gain, persistent DRN activity emerges that stores the learned efficacy of motor commands and adapts future locomotor drive for tens of seconds. The DRN{\textquoteright}s ability to track the effectiveness of motor intent may constitute a computational building block\ for the broader functions of the serotonergic system.

}, doi = {10.1016/j.cell.2016.09.055}, author = {Kawashima, Takashi and Zwart, Maarten F and Yang, Chao-Tsung and Mensh, Brett D and Ahrens, Misha B} } @article {47135, title = {Even-Skipped(+) interneurons are core components of a sensorimotor circuit that maintains left-right symmetric muscle contraction amplitude.}, journal = {Neuron}, volume = {88}, year = {2015}, month = {2015 Oct 21}, pages = {314-29}, abstract = {

Bilaterally symmetric motor patterns-those in which left-right pairs of muscles contract synchronously and with equal amplitude (such as breathing, smiling,\ whisking, and locomotion)-are widespread throughout the animal kingdom. Yet, surprisingly little is known about the underlying neural circuits. We performed a thermogenetic screen to identify neurons required for bilaterally symmetric locomotion in Drosophila larvae and identified the evolutionarily conserved Even-skipped(+) interneurons (Eve/Evx). Activation or ablation of Eve(+) interneurons disrupted bilaterally symmetric muscle contraction amplitude, without affecting the timing of motor output. Eve(+) interneurons are not rhythmically active and thus function independently of the locomotor CPG. GCaMP6 calcium imaging of Eve(+) interneurons in freely moving larvae showed left-right asymmetric activation that correlated with larval behavior. TEM reconstruction of Eve(+) interneuron inputs and outputs showed that the Eve(+) interneurons are at the core of a sensorimotor circuit capable of detecting and modifying body wall muscle contraction.

}, issn = {1097-4199}, doi = {10.1016/j.neuron.2015.09.009}, author = {Heckscher, Ellie S and Zarin, Aref Arzan and Faumont, Serge and Clark, Matthew Q and Manning, Laurina and Fushiki, Akira and Schneider-Mizell, Casey M and Fetter, Richard D and Truman, James W and Zwart, Maarten F and Landgraf, Matthias and Cardona, Albert and Lockery, Shawn R and Doe, Chris Q} }