Central processing of leg proprioception in Drosophila
- University of Washington, United States
- Bangor University, United Kingdom
- Janelia Research Campus, Howard Hughes Medical Institute, United States
Abstract
Proprioception, the sense of self-movement and position, is mediated by mechanosensory neurons that detect diverse features of body kinematics. Although proprioceptive feedback is crucial for accurate motor control, little is known about how downstream circuits transform limb sensory information to guide motor output. Here, we investigate neural circuits in Drosophila that process proprioceptive information from the fly leg. We identify three cell-types from distinct developmental lineages that are positioned to receive input from proprioceptor subtypes encoding tibia position, movement, and vibration. 13Bα neurons encode femur-tibia joint angle and mediate postural changes in tibia position. 9Aα neurons also drive changes in leg posture, but encode a combination of directional movement, high frequency vibration, and joint angle. Activating 10Bα neurons, which encode tibia vibration at specific joint angles, elicits pausing in walking flies. Altogether, our results reveal that central circuits integrate information across proprioceptor subtypes to construct complex sensorimotor representations that mediate diverse behaviors, including reflexive control of limb posture and detection of leg vibration.
Data availability
Data made freely available on Dryad (doi:10.5061/dryad.k3j9kd55t).
-
Central processing of leg proprioception in Drosophila: physiology and behavior dataDryad Digital Repository, doi:10.5061/dryad.k3j9kd55t.
Article and author information
Author details
Funding
National Institutes of Health (R01NS102333)
- Sweta Agrawal
- Evyn S Dickinson
- Anne Sustar
- Pralaksha Gurung
- John C Tuthill
Howard Hughes Medical Institute
- David Shepherd
- James W Truman
Pew Charitable Trusts (Scholar Award)
- Sweta Agrawal
- Evyn S Dickinson
- Anne Sustar
- Pralaksha Gurung
- John C Tuthill
Searle Scholars Program (Scholar Award)
- Sweta Agrawal
- Evyn S Dickinson
- Anne Sustar
- Pralaksha Gurung
- John C Tuthill
Alfred P. Sloan Foundation (Scholar Award)
- Sweta Agrawal
- Evyn S Dickinson
- Anne Sustar
- Pralaksha Gurung
- John C Tuthill
McKnight Endowment Fund for Neuroscience (Scholar Award)
- Sweta Agrawal
- Evyn S Dickinson
- Anne Sustar
- Pralaksha Gurung
- John C Tuthill
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Agrawal et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,420
- views
-
- 395
- downloads
-
- 47
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Central processing of leg proprioception in Drosophila
eLife 9:e60299.
https://doi.org/10.7554/eLife.60299
Further reading
-
- Neuroscience
Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, providing foundations to now optimize neuromodulatory efficacy for human applications. Across multiple studies, one promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition in humans (Fomenko et al., 2020). At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from TUS pulsing at audible frequencies. In this study, we disentangle direct neuromodulatory and indirect auditory contributions to motor inhibitory effects of TUS. To this end, we include tightly matched control conditions across four experiments, one preregistered, conducted independently at three institutions. We employed a combined transcranial ultrasonic and magnetic stimulation paradigm, where TMS-elicited motor-evoked potentials (MEPs) served as an index of corticospinal excitability. First, we replicated motor inhibitory effects of TUS but showed through both tight controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation, not direct neuromodulation. Furthermore, we consider neuromodulation beyond driving overall excitation/inhibition and show preliminary evidence of how TUS might interact with ongoing neural dynamics instead. Primarily, this study highlights the substantial shortcomings in accounting for the auditory confound in prior TUS-TMS work where only a flip-over sham and no active control was used. The field must critically reevaluate previous findings given the demonstrated impact of peripheral confounds. Furthermore, rigorous experimental design via (in)active control conditions is required to make substantiated claims in future TUS studies. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for research and clinical applications.
-
- Medicine
- Neuroscience
Background:
The dichotomy between the hypo- versus hyperkinetic nature of Parkinson’s disease (PD) and dystonia, respectively, is thought to be reflected in the underlying basal ganglia pathophysiology. In this study, we investigated differences in globus pallidus internus (GPi) neuronal activity, and short- and long-term plasticity of direct pathway projections.
Methods:
Using microelectrode recording data collected from the GPi during deep brain stimulation surgery, we compared neuronal spiketrain features between people with PD and those with dystonia, as well as correlated neuronal features with respective clinical scores. Additionally, we characterized and compared readouts of short- and long-term synaptic plasticity using measures of inhibitory evoked field potentials.
Results:
GPi neurons were slower, bustier, and less regular in dystonia. In PD, symptom severity positively correlated with the power of low-beta frequency spiketrain oscillations. In dystonia, symptom severity negatively correlated with firing rate and positively correlated with neuronal variability and the power of theta frequency spiketrain oscillations. Dystonia was moreover associated with less long-term plasticity and slower synaptic depression.
Conclusions:
We substantiated claims of hyper- versus hypofunctional GPi output in PD versus dystonia, and provided cellular-level validation of the pathological nature of theta and low-beta oscillations in respective disorders. Such circuit changes may be underlain by disease-related differences in plasticity of striato-pallidal synapses.
Funding:
This project was made possible with the financial support of Health Canada through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and of the Azrieli Foundation (LM), as well as a grant from the Banting Research Foundation in partnership with the Dystonia Medical Research Foundation (LM).
