Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination
- Leipzig University, Germany
- University Hospital Würzburg, Germany
- University of Hamburg, Germany
- University of Würzburg, Germany
- University Hopsitals of Wuerzburg, Germany
Abstract
Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the Drosophila aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic in vivo experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased Cirl1 expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.
Data availability
The presented data are summarized in Tables 1-3.
Article and author information
Author details
Divya Sachidanandan
Funding
Deutsche Forschungsgemeinschaft (PA3241/2-1)
- Mareike Selcho
Deutsche Forschungsgemeinschaft (RI817/13-1)
- Heike L Rittner
Deutsche Forschungsgemeinschaft (FOR 2149/P03,TRR 166/B04,KI1460/4-1,KI1460/5-1)
- Robert J Kittel
Deutsche Forschungsgemeinschaft (SPP 1926/SO1337/2-2,SO1337/4-1)
- Peter Soba
Deutsche Forschungsgemeinschaft (FOR 2149/P01 and P03)
- Tobias Langenhan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal care and protocols were performed in accordance with international guidelines for the care and use of laboratory animals (EU Directive 2010/63/EU for animal experiments) and were approved by the Government of Unterfranken (protocol numbers 2-733 and 2-264).
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Publication history
- Received: March 13, 2020
- Accepted: September 17, 2020
- Accepted Manuscript published: September 30, 2020 (version 1)
- Version of Record published: October 9, 2020 (version 2)
Copyright
© 2020, Dannhäuser 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
-
- 1,407
- Page views
-
- 201
- Downloads
-
- 6
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
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)
Further reading
-
- Neuroscience
Strong gamma-band oscillations in primate early visual cortex can be induced by homogeneous color surfaces (Peter et al., 2019; Shirhatti and Ray, 2018). Compared to other hues, particularly strong gamma oscillations have been reported for red stimuli. However, precortical color processing and the resultant strength of input to V1 have often not been fully controlled for. Therefore, stronger responses to red might be due to differences in V1 input strength. We presented stimuli that had equal luminance and cone contrast levels in a color coordinate system based on responses of the lateral geniculate nucleus, the main input source for area V1. With these stimuli, we recorded magnetoencephalography in 30 human participants. We found gamma oscillations in early visual cortex which, contrary to previous reports, did not differ between red and green stimuli of equal L-M cone contrast. Notably, blue stimuli with contrast exclusively on the S-cone axis induced very weak gamma responses, as well as smaller event-related fields and poorer change-detection performance. The strength of human color gamma responses for stimuli on the L-M axis could be well explained by L-M cone contrast and did not show a clear red bias when L-M cone contrast was properly equalized.
-
- Neuroscience
Resolving trajectories of axonal pathways in the primate prefrontal cortex remains crucial to gain insights into higher-order processes of cognition and emotion, which requires a comprehensive map of axonal projections linking demarcated subdivisions of prefrontal cortex and the rest of brain. Here, we report a mesoscale excitatory projectome issued from the ventrolateral prefrontal cortex (vlPFC) to the entire macaque brain by using viral-based genetic axonal tracing in tandem with high-throughput serial two-photon tomography, which demonstrated prominent monosynaptic projections to other prefrontal areas, temporal, limbic, and subcortical areas, relatively weak projections to parietal and insular regions but no projections directly to the occipital lobe. In a common 3D space, we quantitatively validated an atlas of diffusion tractography-derived vlPFC connections with correlative green fluorescent protein-labeled axonal tracing, and observed generally good agreement except a major difference in the posterior projections of inferior fronto-occipital fasciculus. These findings raise an intriguing question as to how neural information passes along long-range association fiber bundles in macaque brains, and call for the caution of using diffusion tractography to map the wiring diagram of brain circuits.
