Mechanotransduction events at the physiological site of touch detection
Abstract
Afferents of peripheral mechanoreceptors innervate the skin of vertebrates, where they detect physical touch via mechanically gated ion channels (mechanotransducers). While the afferent terminal is generally understood to be the primary site of mechanotransduction, the functional properties of mechanically activated (MA) ionic current generated by mechanotransducers at this location remain obscure. Until now, direct evidence of MA current and mechanically induced action potentials in the mechanoreceptor terminal has not been obtained. Here, we report patch-clamp recordings from the afferent terminal innervating Grandry (Meissner) corpuscles in the bill skin of a tactile specialist duck. We show that mechanical stimulation evokes MA current in the afferent with fast kinetics of activation and inactivation during the dynamic phases of the mechanical stimulus. These responses trigger rapidly adapting firing in the afferent detected at the terminal and in the afferent fiber outside of the corpuscle. Our findings elucidate the initial electrogenic events of touch detection in the mechanoreceptor nerve terminal.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 1 and 2.
Article and author information
Author details
Funding
National Science Foundation (1923127)
- Sviatoslav N Bagriantsev
National Science Foundation (2114084)
- Sviatoslav N Bagriantsev
National Science Foundation (1754286)
- Elena O Gracheva
National Institutes of Health (R01NS097547)
- Sviatoslav N Bagriantsev
National Institutes of Health (R01NS126277)
- Sviatoslav N Bagriantsev
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments with duck embryos (Anas platyrhynchos domesticus) were approved by and performed in accordance with guidelines of the Institutional Animal Case and Use Committee of Yale University, protocol 11526.
Copyright
© 2023, Ziolkowski 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
-
- 1,801
- views
-
- 270
- downloads
-
- 7
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
Insulin plays a critical role in maintaining metabolic homeostasis. Since metabolic demands are highly dynamic, insulin release needs to be constantly adjusted. These adjustments are mediated by different pathways, most prominently the blood glucose level, but also by feedforward signals from motor circuits and different neuromodulatory systems. Here, we analyze how neuromodulatory inputs control the activity of the main source of insulin in Drosophila – a population of insulin-producing cells (IPCs) located in the brain. IPCs are functionally analogous to mammalian pancreatic beta cells, but their location makes them accessible for in vivo recordings in intact animals. We characterized functional inputs to IPCs using single-nucleus RNA sequencing analysis, anatomical receptor expression mapping, connectomics, and an optogenetics-based ‘intrinsic pharmacology’ approach. Our results show that the IPC population expresses a variety of receptors for neuromodulators and classical neurotransmitters. Interestingly, IPCs exhibit heterogeneous receptor profiles, suggesting that the IPC population can be modulated differentially. This is supported by electrophysiological recordings from IPCs, which we performed while activating different populations of modulatory neurons. Our analysis revealed that some modulatory inputs have heterogeneous effects on the IPC activity, such that they inhibit one subset of IPCs, while exciting another. Monitoring calcium activity across the IPC population uncovered that these heterogeneous responses occur simultaneously. Certain neuromodulatory populations shifted the IPC population activity towards an excited state, while others shifted it towards inhibition. Taken together, we provide a comprehensive, multi-level analysis of neuromodulation in the insulinergic system of Drosophila.
-
- Neuroscience
As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other central nervous system (CNS) injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience. Glial cells support CNS homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil-associated glia (NG) in Drosophila, equivalent to vertebrate astrocytes, oligodendrocytes (OL), and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between ensheathing glia (EG) and astrocyte-like glia (ALG). Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.