Imaging fictive locomotor patterns in larval<i>Drosophila</i>

Pulver, Stefan R.; Bayley, T. G.; Taylor, Adam L.; Berni, Jimena; Bate, Michael; Hedwig, Berthold

doi:10.1152/jn.00731.2015

Cited by 122 publications

(184 citation statements)

References 95 publications

Supporting

Mentioning

159

Contrasting

Order By: Relevance

“…Intensities of neuronal activation were found to be higher during BW and FW compared to AT and PT. We also confirmed that AT but not other motor patterns shows strongly asymmetric activity as previously reported 13 . It has been known that transition between different motor patterns in behaving larvae is biased 30,31 .…”

Section: Introductionsupporting

confidence: 92%

Data-driven analysis of motor activity implicates 5-HT2A neurons in backward locomotion of larvalDrosophila

Park

Kondo

Tanimoto

et al. 2018

Preprint

View full text Add to dashboard Cite

Rhythmic animal behaviors are regulated in part by neural circuits called the central pattern generators (CPGs). Classifying neural activities correlated with body movements and identifying component neurons associated with the activities are critical steps in understanding the workings of CPGs and animal locomotion. Here, we present a novel method for classifying motor activities in large-scale calcium imaging data of Drosophila larvae. The method is based on pre-trained convolutional neural network model VGG-16 and unsupervised learning, and successfully classified activities correlated with forward and backward locomotion in activity data of different types of neurons and under different imaging conditions. We also used voxel-wise correlation mapping to identify neurons associated with each motor activity. By applying these methods to neurons targeted by 5-HT2A-GAL4, which we generated by CRISPR/Cas9-mediated gene knock-in, we identified two classes of interneurons, termed Seta and Leta, which are specifically active during backward but not forward fictive locomotion. Optogenetic activation of Seta and Leta neurons increases backward locomotion. Conversely, thermogenetic inhibition of 5-HT2A-GAL4 neurons or application of a 5-HT2 antagonist decreased backward locomotion induced by noxious light stimuli. Our results suggest that 5-HT modulates backward locomotion by acting on Seta and Leta neurons via the 5-HT2A receptor. This study establishes an accelerated pipeline for activity profiling and cell identification in larval Drosophila and implicates a serotonergic system in the modulation of backward locomotion.

show abstract

Section: Introductionsupporting

confidence: 92%

Data-driven analysis of motor activity implicates 5-HT2A neurons in backward locomotion of larvalDrosophila

Park

Kondo

Tanimoto

et al. 2018

Preprint

View full text Add to dashboard Cite

show abstract

“…However, as described previously 30 , occasionally a spike occurred alongside a coincident trough in GCaMP6m fluorescence in the contralateral motoneuron dendrite (Fig. 4B).…”

Section: The Pnkd3 Mutation Disrupts Cpg Activity In the Larval Ventrsupporting

confidence: 83%

“…The function of pre-motor circuits and motoneurons driving larval locomotion can be interrogated via sharp electrode recordings and ex vivo calcium imaging [29][30][31] . Furthermore, the neuromuscular junction (NMJ) of Drosophila larvae represents a widely studied model glutamatergic synapse in which alterations in neurotransmitter release and/or synaptic plasticity can be readily assessed 32 .…”

Section: Introductionmentioning

confidence: 99%

Altered synaptic plasticity and central pattern generator dysfunction in aDrosophilamodel of PNKD3 paroxysmal dyskinesia

Lowe

Krätschmer

Jepson

2020

Preprint

View full text Add to dashboard Cite

Background: Paroxysmal non-kinesigenic dyskinesia type-3 (PNKD3) has been linked to gain-of-function (GOF) mutations in the hSlo1 BK potassium channel, in particular a dominant mutation (D434G) that enhances Ca 2+ -sensitivity. However, while BK channels play well-known roles in regulating neurotransmitter release, it is unclear whether the D434G mutation alters neurotransmission and synaptic plasticity in vivo. Furthermore, the subtypes of movement-regulating circuits impacted by this mutation are unknown. Objectives:We aimed to use a larval Drosophila model of PNKD3 (slo E366G/+ ) to examine how BK channel GOF in dyskinesia alters synaptic properties and motor circuit function. Methods:We used video-tracking to test for movement defects in slo E366G/+ larvae, and sharp-electrode recordings to assess the fidelity of Ca 2+ -dependent neurotransmitter release and short-term plasticity at the neuromuscular junction. We then combined sharp-electrode recording with ex vivo Ca 2+ -imaging to investigate the functionality of the central pattern generator (CPG) driving foraging behavior in slo E366G/+ larvae. Results:We show that the PNKD3 mutation leads to Ca 2+ -dependent alterations in synaptic release and paired-pulse facilitation. Furthermore, we identify robust alterations in locomotor behaviors in slo E366G/+ larvae which were mirrored by dysfunction of the upstream, movement-generating CPG in the larval ventral nerve cord. Conclusion:Our results demonstrate that a BK channel GOF mutation can alter neurotransmitter release and short-term synaptic plasticity, and result in CPG dysfunction, in Drosophila larvae. These data add to a growing body of work linking paroxysmal dyskinesias to aberrant neuronal excitability and synaptic plasticity in pre-motor circuits.

show abstract

“…The work presented here also stands in contrast to previous models of larval 673 peristalsis [38,40] and the prevailing hypotheses regarding this phenomenon [15,58] by 674 eschewing any role for intrinsic neural dynamics. Such stereotyped and rhythmic 675 locomotion is widely assumed to be the signature of a central pattern generator (CPG), 676 that is, a neural circuit that intrinsically generates a rhythmic output, and thus 677 determines a particular mechanical trajectory to be followed by the body [59][60][61].…”

mentioning

confidence: 60%

Mechanics of exploration inDrosophila melanogaster

Loveless

Lagogiannis

Webb

2018

Preprint

View full text Add to dashboard Cite

The Drosophila larva executes a stereotypical exploratory routine that appears to consist of stochastic alternation between straight peristaltic crawling and reorientation events through lateral bending. We present a model of larval mechanics for axial and transverse motion over a planar substrate, and use it to develop a simple, reflexive neuromuscular model from physical principles. In the absence of damping and driving, the mechanics of the body produces axial travelling waves, lateral oscillations, and unpredictable, chaotic deformations. The neuromuscular system counteracts friction to recover these motion patterns, giving rise to forward and backward peristalsis in addition to turning. The model produces spontaneous exploration, even though the model nervous system has no intrinsic pattern generating or decision making ability, and neither senses nor drives bending motions. Ultimately, our model suggests a novel view of larval exploration as a deterministic superdiffusion process which is mechanistically grounded in the chaotic mechanics of the body. 7 Drosophila larva executes a stereotypical exploratory routine [1] which appears to 8 consist of a series of straight runs punctuated by reorientation events [2]. Straight runs 9 are produced by laterally symmetric peristaltic compression waves, which propagate 10 along the larval body in the same direction as overall motion (i.e. posterior-anterior 11 waves carry the larva forwards relative to the substrate, anterior-posterior waves carry 12 the larva backwards) [3]. Reorientation is brought about by laterally asymmetric 13 compression and expansion of the most anterior body segments of the larva, which 14 causes the body axis of the larva to bend [2].15Peristaltic crawling and reorientation are commonly thought to constitute discrete 16 behavioural states, driven by distinct motor programs [2]. In exploration, it is assumed, 17 alternation between these states occurs stochastically, allowing the larva to search its 18 environment through an unbiased random walk [1,[4][5][6]. The state transitions or 19 direction and magnitude of turns can be biased by sensory input to produce taxis 20 PLOS 1/27 behaviours [4, 5, 7-13]. The neural circuits involved in producing the larval exploratory 21 routine potentially lie within the ventral nerve cord (VNC), since silencing the synaptic 22 communication within the brain and subesophageal ganglia (SOG) does not prevent 23 substrate exploration [1]. Electrophysiological and optogenetic observations of fictive 24 locomotion patterns within the isolated VNC [14, 15] support the prevailing hypothesis 25 that the exploratory routine is primarily a result of a centrally generated motor pattern. 26 As such, much recent work has focused on identifying and characterising the cells and 27 circuits within the larval VNC [16-32]. However, behaviour rarely arises entirely from 28 central mechanisms; sensory feedback and biomechanics often play a key role [33, 34] 29including the potential introduction of stochasticity. Indeed, thermog...

show abstract

Imaging fictive locomotor patterns in larvalDrosophila

Cited by 122 publications

References 95 publications

Data-driven analysis of motor activity implicates 5-HT2A neurons in backward locomotion of larvalDrosophila

Data-driven analysis of motor activity implicates 5-HT2A neurons in backward locomotion of larvalDrosophila

Altered synaptic plasticity and central pattern generator dysfunction in aDrosophilamodel of PNKD3 paroxysmal dyskinesia

Mechanics of exploration inDrosophila melanogaster

Contact Info

Product

Resources

About