A microRNA that controls the emergence of embryonic movement DOI Creative Commons
Jonathan A. C. Menzies, André Maia Chagas, Tom Baden

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Июнь 13, 2024

Movement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here, we investigate the genetic basis underlying onset movement in Drosophila focusing on role played by small non-coding RNAs (microRNAs, miRNAs). To this end, first develop quantitative behavioural pipeline capable tracking large populations fly embryos, and using system, discover that miRNA miR-2b-1 plays emergence movement. Through combination spectral analysis motor patterns, cell sorting RNA situs, reconstitution tests, neural optical imaging define influences exerting actions developing nervous system. Furthermore, through bioinformatics coupled to manipulation expression phenocopy tests identify previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene – which term Mo vement Modula tor ( Motor ) as target mechanistically links Cell-specific null mutant background, followed assays analyses, suggest affects effects sensory elements circuitry, rather than domain. Our work thus reports system regulating movement, suggesting other miRNAs likely play developmental process well species.

Язык: Английский

Sleep, plasticity, and sensory neurodevelopment DOI Creative Commons
Mark S. Blumberg, James C. Dooley, Alexandre Tiriac

и другие.

Neuron, Год журнала: 2022, Номер 110(20), С. 3230 - 3242

Опубликована: Сен. 8, 2022

Язык: Английский

Процитировано

44
Balance of activity during a critical period tunes a developing network DOI Creative Commons
Iain Hunter,

Bramwell Coulson,

Tom Pettini

и другие.

eLife, Год журнала: 2024, Номер 12

Опубликована: Янв. 9, 2024

Developing neural circuits are influenced by activity and especially sensitive to changes in during critical periods (CPs) of development. Changes occurring a CP often become ‘locked in’ so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked excessive such periods. It is, therefore, important identify those aspects circuit development CP. In this study, we take advantage genetic tractability Drosophila show perturbation an embryonic permanently alters properties locomotor circuit. Specific include increased synchronicity motoneuron greater strengthening excitatory over inhibitory synaptic drive motoneurons. These sufficient reduce network robustness, evidenced sensitivity induced seizure. We also can rescue these when is mitigated inhibition provided mechanosensory neurons. Similarly, demonstrate dose-dependent relationship between experienced extent which it possible hyperexcitable phenotype characteristic para bss mutation. This suggests developing must be exposed properly balanced sum excitation achieve normal function. Our results, provide novel insight into how shapes specific elements circuit, period integrated tune environment will likely

Язык: Английский

Процитировано

7
Modulation of a critical period for motor development in Drosophila by BK potassium channels DOI Creative Commons
Simon A. Lowe, Abigail D. Wilson, Gabriel Aughey

и другие.

Current Biology, Год журнала: 2024, Номер 34(15), С. 3488 - 3505.e3

Опубликована: Июль 24, 2024

Язык: Английский

Процитировано

3
Characterizing stage-dependent neuromotor patterns in Drosophila melanogaster larvae through a graph construction approach DOI Creative Commons

Yuri Bilk Matos,

Nadezhda Velichkova,

Mateo Kirchknopf Riera

и другие.

Frontiers in Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Март 20, 2025

We investigated developmental changes in neuromotor activity patterns Drosophila melanogaster larvae by combining calcium imaging with a novel graph-based mathematical framework. This allows to perform relevant quantitative comparisons between first (L1) and early third (L3) instar larvae. found that L1 exhibit higher frequencies of spontaneous neural fail propagate, indicating less mature system. In contrast, L3 show efficient initiation propagation along the entire ventral nerve cord (VNC), resulting longer chains. The time chain VNC is shorter than L3, probably reflecting increased length VNC. On other hand, peristaltic waves through whole body during locomotion much faster L1, so correlating velocities greater dispersal rates. Hence, VNC-body interaction determines characteristics crawling Further, asymmetrical neuronal activity, predominantly anterior segments larvae, was associated turning behaviors enhanced navigation. These findings illustrate proposed model provides systematic method analyze across stages, for instance, helping uncover maturation stages circuits their role locomotion.

Язык: Английский

Процитировано

0
Balance of activity during a critical period tunes a developing network DOI Creative Commons
Iain Hunter,

Bramwell Coulson,

Tom Pettini

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Окт. 4, 2023

Developing neural circuits are influenced by activity and especially sensitive to changes in during critical periods (CPs) of development. Changes occurring a CP often become 'locked in' so that they affect the mature network. Indeed, several neurodevelopmental disorders have been linked excessive such periods. It is, therefore, important identify those aspects circuit development CP. In this study, we take advantage genetic tractability Drosophila show perturbation an embryonic permanently alters properties locomotor circuit. Specific include increased synchronicity motoneuron greater strengthening excitatory over inhibitory synaptic drive motoneurons. These sufficient reduce network robustness, evidenced sensitivity induced seizure. We also can rescue these when is mitigated inhibition provided mechanosensory neurons. Similarly, demonstrate dose-dependent relationship between experienced extent which it possible hyperexcitable phenotype characteristic parabss mutation. This suggests developing must be exposed properly balanced sum excitation achieve normal function. Our results, provide novel insight into how shapes specific elements circuit, period integrated tune environment will likely

Язык: Английский

Процитировано

8
Critical periods in Drosophila neural network development: Importance to network tuning and therapeutic potential DOI Creative Commons

Bramwell Coulson,

Iain Hunter, Sarah J. Doran

и другие.

Frontiers in Physiology, Год журнала: 2022, Номер 13

Опубликована: Дек. 2, 2022

Critical periods are phases of heightened plasticity that occur during the development neural networks. Beginning with pioneering work Hubel and Wiesel, which identified a critical period for formation ocular dominance in mammalian visual network connectivity, have been many circuits, both sensory motor, across phyla, suggesting universal phenomenon. However, key unanswered question remains why these forms restricted to specific developmental rather than being continuously present. The consequence this temporal restriction is activity perturbations can lasting significant functional consequences mature From perspective, might enable reproducibly robust function emerge from ensembles cells, whose properties necessarily variable fluctuating. also offer clinical opportunity. Imposed perturbation has shown remarkable beneficial outcomes range animal models neurological disease including epilepsy. In review, we spotlight recent identification locomotor Drosophila larva describe how studying model organism, because its simplified nervous system an almost complete wired connectome, offers attractive prospect understanding impacts neuronal network.

Язык: Английский

Процитировано

12
A microRNA that controls the emergence of embryonic movement DOI Creative Commons
Jonathan A. C. Menzies, André Maia Chagas, Tom Baden

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Март 20, 2024

Movement is a key feature of animal systems, yet its embryonic origins are not fully understood. Here, we investigate the genetic basis underlying onset movement in Drosophila focusing on role played by small non-coding RNAs (microRNAs, miRNAs). To this end, first develop quantitative behavioural pipeline capable tracking large populations fly embryos, and using system, discover that miRNA miR-2b-1 plays emergence movement. Through combination spectral analysis motor patterns, cell sorting RNA situs, reconstitution tests, neural optical imaging define influences exerting actions developing nervous system. Furthermore, through bioinformatics coupled to manipulation expression phenocopy tests identify previously uncharacterised (but evolutionarily conserved) chloride channel encoding gene – which term Mo vement Modula tor ( Motor ) as target mechanistically links Cell-specific null mutant background, followed assays analyses, suggest affects effects sensory elements circuitry, rather than domain. Our work thus reports system regulating movement, suggesting other miRNAs likely play developmental process well species.

Язык: Английский

Процитировано

2
Developmentally Unique Cerebellar Processing Prioritizes Self- over Other-Generated Movements DOI
Angela M. Richardson, Greta Sokoloff, Mark S. Blumberg

и другие.

Journal of Neuroscience, Год журнала: 2024, Номер 44(19), С. e2345232024 - e2345232024

Опубликована: Апрель 8, 2024

Animals must distinguish the sensory consequences of self-generated movements (reafference) from those other-generated (exafference). Only entail production motor copies (i.e., corollary discharges), which are compared with reafference in cerebellum to compute predictive or internal models movement. Internal emerge gradually over first three postnatal weeks rats through a process that is not yet fully understood. Previously, we demonstrated day (P) 8 and P12 precerebellar nuclei convey discharge during active (REM) sleep when pups produce limb twitches. Here, recording deep cerebellar nucleus (interpositus, IP) both sexes, reafferent exafferent responses twitches stimulations, respectively. As expected, most IP units showed robust However, contrast other structures throughout brain, relatively few responses. Upon finding occurred under urethane anesthesia, hypothesized inhibits cortical cells, thereby disinhibiting IP. In support this hypothesis, ablating tissue dorsal mimicked effects on exafference. Finally, results suggest twitch-related conveyed simultaneously parallel cortex Based these results, propose provide opportunities for nascent integrate somatotopically organized reafference, enabling development closed-loop circuits and, subsequently, models.

Язык: Английский

Процитировано

2
Steering From the Rear: Coordination of Central Pattern Generators Underlying Navigation by Ascending Interneurons DOI Creative Commons
Julius Jonaitis, Karen L Hibbard,

Kaity McCafferty Layte

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 17, 2024

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

Язык: Английский

Процитировано

2
Critical developmental periods of vulnerability in dystonia DOI Creative Commons
Simon A. Lowe

Dystonia, Год журнала: 2024, Номер 3

Опубликована: Март 13, 2024

Dystonia is a heterogenous movement disorder characterised by involuntary muscle contractions, leading to abnormal postures and movements. Despite being the third most common disorder, pathophysiological mechanisms causing dystonia are incompletely understood. Isolated often caused pathogenic mutations in single genes. An emerging body of evidence suggests that at least some forms isolated have strong developmental component, with effects acting within discrete periods increased vulnerability during neurodevelopment. The extent which this feature genetically distinct dystonia, might be disrupted these periods, remains unclear. During critical development, neuronal activity instructive maturation circuits, inappropriate levels period can lead permanent defects. This review, an intentional focus on our work, outlines implicating disruptions as potential mechanism underlying inherited motor disorders general, particular.

Язык: Английский

Процитировано

1