Mechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to localized forces, consistent with them being able to detect the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and possibly also active signal propagation in dendrites contribute to the sensory features of c4da. In particular, we discover that Piezo and Ppk1/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensitivity of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.
All data generated or analysed during this study are included in the manuscript and supporting files. The source data for all plots have been provided as Excel files.
Fly Cell Atlas: single-cell transcriptomes of the entire adult Drosophila - Smartseq2 datasetEMBL-EBI ArrayExpress, E-MTAB-10628.
The Fly Cell Atlas: single-cell transcriptomes of the entire adult Drosophila - 10x datasetEMBL-EBI ArrayExpress, E-MTAB-10519.
- Xin Liang
- Xin Liang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Matthieu Louis, University of California, Santa Barbara, United States
© 2022, Liu 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.
Even though human experience unfolds continuously in time, it is not strictly linear; instead, it entails cascading processes building hierarchical cognitive structures. For instance, during speech perception, humans transform a continuously varying acoustic signal into phonemes, words, and meaning, and these levels all have distinct but interdependent temporal structures. Time-lagged regression using temporal response functions (TRFs) has recently emerged as a promising tool for disentangling electrophysiological brain responses related to such complex models of perception. Here we introduce the Eelbrain Python toolkit, which makes this kind of analysis easy and accessible. We demonstrate its use, using continuous speech as a sample paradigm, with a freely available EEG dataset of audiobook listening. A companion GitHub repository provides the complete source code for the analysis, from raw data to group level statistics. More generally, we advocate a hypothesis-driven approach in which the experimenter specifies a hierarchy of time-continuous representations that are hypothesized to have contributed to brain responses, and uses those as predictor variables for the electrophysiological signal. This is analogous to a multiple regression problem, but with the addition of a time dimension. TRF analysis decomposes the brain signal into distinct responses associated with the different predictor variables by estimating a multivariate TRF (mTRF), quantifying the influence of each predictor on brain responses as a function of time(-lags). This allows asking two questions about the predictor variables: 1) Is there a significant neural representation corresponding to this predictor variable? And if so, 2) what are the temporal characteristics of the neural response associated with it? Thus, different predictor variables can be systematically combined and evaluated to jointly model neural processing at multiple hierarchical levels. We discuss applications of this approach, including the potential for linking algorithmic/representational theories at different cognitive levels to brain responses through computational models with appropriate linking hypotheses.
The functional complementarity of the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) allows for optimal combined gaze stabilization responses (CGR) in light. While sensory substitution has been reported following complete vestibular loss, the capacity of the central vestibular system to compensate for partial peripheral vestibular loss remains to be determined. Here, we first demonstrate the efficacy of a 6-week subchronic ototoxic protocol in inducing transient and partial vestibular loss which equally affects the canal- and otolith-dependent VORs. Immunostaining of hair cells in the vestibular sensory epithelia revealed that organ-specific alteration of type I, but not type II, hair cells correlates with functional impairments. The decrease in VOR performance is paralleled with an increase in the gain of the OKR occurring in a specific range of frequencies where VOR normally dominates gaze stabilization, compatible with a sensory substitution process. Comparison of unimodal OKR or VOR versus bimodal CGR revealed that visuo-vestibular interactions remain reduced despite a significant recovery in the VOR. Modeling and sweep-based analysis revealed that the differential capacity to optimally combine OKR and VOR correlates with the reproducibility of the VOR responses. Overall, these results shed light on the multisensory reweighting occurring in pathologies with fluctuating peripheral vestibular malfunction.