GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving<i>Drosophila</i>

Gowda, Swetha B. M.; Paranjpe, Pushkar; Reddy, O. Venkateshwara; Palliyil, Sudhir; Reichert, Heinrich; VijayRaghavan, K.

doi:10.1101/173120

Cited by 6 publications

(8 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In Drosophila larvae, a set of inhibitory local interneurons, termed period-positive median segmental interneurons (PMSIs) control the frequency and speed of peristaltic locomotion by limiting the duration of motoneuronal bursting (Kohsaka et al, 2014). In adult Drosophila, similar yet unidentified inhibitory premotor input to leg motoneurons is associated with walking speed and their inactivation reveals an underlying slower walking speed (Gowda et al, 2018). In contrast, a lesion of the crossed glycinergic fibers or blocking glycinergic transmission in the lamprey spinal cord increase fictive burst frequency (Grillner, 2003).…”

Section: A Fundamental Role For Inhibition In Rapid Locomotionmentioning

confidence: 99%

“…Moreover, when excitation is blocked, reciprocal inhibition can sustain a minimal circuit for rhythmic flexor-extensor alternation based on postinhibitory rebound (Talpalar et al, 2011). Premotor inhibition is necessary for rapid locomotion in insects (Gowda et al, 2018Kohsaka et al, 2014, amphibians (Li and Moult, 2012), fish (Liao and Fetcho, 2008;Satou et al, 2009) and mammals (Gosgnach et al, 2006;Kiehn, 2016;Zhang et al, 2014), as well as for rapid respiratory rhythm (Cregg et al, 2017). Across fields disparate from neuroscience, through ecological and genetic networks, to pedestrian and vehicle traffic, negative regulation plays a role in modulating and coordinating the performance of system-parts to overall speed up processes of complex systems (Gershenson and Helbing, 2015).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition Underlies Fast Undulatory Locomotion inCaenorhabditis elegans

Deng

Denham

Arya

et al. 2020

eNeuro

View full text Add to dashboard Cite

Inhibition plays important roles in modulating the neural activities of sensory and motor systems at different levels from synapses to brain regions. To achieve coordinated movement, motor systems produce alternating contraction of antagonist muscles, whether along the body axis or within and among limbs, which often involves direct or indirect cross-inhibitory pathways. In the nematode C. elegans, a small network involving excitatory cholinergic and inhibitory GABAergic motoneurons generates the dorsoventral alternation of body-wall muscles that supports undulatory locomotion. Inhibition has been suggested to be necessary for backward undulation because mutants that are defective in GABA transmission exhibit a shrinking phenotype in response to a harsh touch to the head, whereas wild-type animals produce a backward escape response. Here, we demonstrate that the shrinking phenotype is exhibited by wildtype as well as mutant animals in response to harsh touch to the head or tail, but only GABA transmission mutants show slow locomotion after stimulation. Impairment of GABA transmission, either genetically or optogenetically, induces lower undulation frequency and lower translocation speed during crawling and swimming in both directions. The activity patterns of GABAergic motoneurons are different during low and high frequency undulation. During low frequency undulation, GABAergic VD and DD motoneurons show correlated activity patterns, while during high frequency undulation, their activity alternates. The experimental results suggest at least three non-mutually exclusive roles for inhibition that could underlie fast undulatory locomotion in C. elegans, which we tested with computational models: cross-inhibition or disinhibition of body-wall muscles, or inhibitory reset. Significance StatementInhibition serves multiple roles in the generation, maintenance, and modulation of the locomotive program and supports the alternating activation of antagonistic muscles. To better understand the role of inhibition in locomotion, we used C. elegans as an animal model, and challenged a prevalent hypothesis that cross-inhibition supports the dorsoventral alternation only during backward locomotion. We find that inhibition is not necessary for muscle alternation during slow undulation in either forward or backward locomotion; however, it is crucial to sustain rapid dorsoventral alternation. We combined behavior analysis and calcium imaging of motoneurons and muscle cells with computational models to test hypotheses for the role of inhibition in locomotion.

show abstract

Section: A Fundamental Role For Inhibition In Rapid Locomotionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inhibition Underlies Fast Undulatory Locomotion inCaenorhabditis elegans

Deng

Denham

Arya

et al. 2020

eNeuro

View full text Add to dashboard Cite

show abstract

“…Notably, this mating interaction requires not only auditory interactions, but also the coordination of wing movement to match the frequencies of corresponding partners (Robert 2009). While uncharacterized in mosquitoes, Drosophila leg and wing muscles are innervated with glutamatergic neurons, and, not surprisingly, the malfunction of these neurons impairs fly movement (Sadaf et al 2015; Gowda et al 2018). Inasmuch as Anopheles mosquitoes rely on muscle coordination to achieve a matching of wing-beat frequencies between females and males for mating recognition (Pennetier et al 2010), the absence of AcAmt function may impact neuronal function to impair muscle control and the auditory/wing beat frequency convergence required during mating.…”

Section: Discussionmentioning

confidence: 99%

Mutagenesis of the Ammonium TransporterAcAmtReveals a Reproductive Role and a Novel Ammonia-Sensing Mechanism in the Malaria Vector MosquitoAnopheles coluzzii

Z¹,

F²,

St³

et al. 2021

Preprint

View full text Add to dashboard Cite

Anopheline mosquitoes are the sole vectors of malaria and rely on olfactory cues for host seeking in which ammonia derived from human sweat plays an essential role. To investigate the function of the Anopheles coluzzii ammonium transporter (AcAmt) in the mosquito olfactory system, we generated an AcAmt null mutant line using CRISPR/Cas9. AcAmt-/- mutants displayed a series of novel phenotypes compared with wild-type mosquitoes including significantly lower insemination rates during mating and increased mortality during eclosion. Furthermore, AcAmt-/- males showed significantly lower sugar consumption while AcAmt-/- females and pupae displayed significantly higher ammonia levels than their wild-type counterparts. Surprisingly, in contrast to previous studies in Drosophila that revealed that the mutation of the ammonium transporter (DmAmt) induces a dramatic reduction of ammonia responses in antennal coeloconic sensilla, no significant differences were observed across a range of peripheral sensory neuron responses to ammonia and other odorants between wild-type and AcAmt-/- females. Taken together, these data support the existence of a unique ammonia-sensing mechanism in mosquitoes and that the ammonium transporter may be an important molecular target for vector control.

show abstract

“…not requiring user input). One uses thresholding and dynamic masking methods (TDM) to automatically identify leg tips 22,31 , while two recent studies employ deep learning algorithms 25,26 using user-annotated training sets. We first compared the performance of FLLIT against TDMbased software provided by Isakov, et.…”

Section: Side-by-side Performance Comparisonmentioning

confidence: 99%

Automated leg tracking reveals distinct conserved gait and tremor signatures inDrosophilamodels of Parkinson’s Disease and Spinocerebellar ataxia 3

Tan

Govindarajan

et al. 2018

Preprint

View full text Add to dashboard Cite

Genetic models in Drosophila have made invaluable contributions to our understanding of the molecular mechanisms underlying neurodegeneration. In human patients, some neurodegenerative diseases lead to characteristic movement dysfunctions, such as abnormal gait and tremors. However, it is currently unknown whether similar movement defects occur in the respective fly models, which could be used to model and better understand the pathophysiology of movement disorders. To address this question, we developed a machine-learning image-analysis programme -Feature Learning-based LImb segmentation and Tracking (FLLIT) -that automatically tracks leg claw positions of freely moving flies recorded on highspeed video, generating a series of body and leg movement parameters. Of note, FLLIT requires no user input for learning. We used FLLIT to characterise fly models of Parkinson's Disease (PD) and Spinocerebellar ataxia 3 (SCA3).Between these models, walking gait and tremor characteristics differed markedly, and recapitulated signatures of the respective human diseases.Selective expression of mutant SCA3 in dopaminergic neurons led to phenotypes resembling that of PD flies, suggesting that the behavioural phenotype may depend on the circuits affected, rather than the specific nature of the mutation. Different mutations produced tremors in distinct leg pairs, indicating that different motor circuits are affected. Almost 190,000 video frames were tracked in this study, allowing, for the first time, high-throughput analysis of gait and tremor features in Drosophila mutants. As an efficient assay of mutant gait and tremor features in an important model system, FLLIT will enable the analysis of the neurogenetic mechanisms that underlie movement disorders.(n = 10), mir-263a KO (n = 11), ple-Gal4>SCA3-flQ27 (n = 14), ple-Gal4>SCA3-flQ84 (n = 15). P values were calculated using a non-parametric Mann-Whitney test except for park 1 and mir-263a KO which shared the same control (yw), hence, P was calculated using a non-parametric Kruskal-Wallis test with Dunn's multiple comparisons post-hoc test (See Fig. S5).See also Videos 2 -6.

show abstract

GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely movingDrosophila

Abstract: 25Walking is a complex rhythmic locomotor behaviour generated by

Cited by 6 publications

References 44 publications

Inhibition Underlies Fast Undulatory Locomotion inCaenorhabditis elegans

Inhibition Underlies Fast Undulatory Locomotion inCaenorhabditis elegans

Mutagenesis of the Ammonium TransporterAcAmtReveals a Reproductive Role and a Novel Ammonia-Sensing Mechanism in the Malaria Vector MosquitoAnopheles coluzzii

Automated leg tracking reveals distinct conserved gait and tremor signatures inDrosophilamodels of Parkinson’s Disease and Spinocerebellar ataxia 3

Contact Info

Product

Resources

About