In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP

Emery, Edward C.; Luiz, Ana Paula; Sikandar, Shafaq; Magnúsdóttir, Rán; Dong, Xinzhong; Wood, John N.

doi:10.1126/sciadv.1600990

Cited by 102 publications

(138 citation statements)

References 30 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…Indomethacin was included to reduce the potential complicating factor of endogenous cyclooxygenase products sensitizing C‐fibres over time (Emery et al . ). For the intra‐arterial delivery of chemicals, the 10 mm long steel tip of a 33 gauge needle attached to PE‐10 tubing (OD 0.61 mm, ID 0.28 mm) was inserted into the right subscapular artery, the blood in the skin preparation was flushed with buffer, and the needle was secured with surgical silk.…”

Section: Methodsmentioning

confidence: 97%

Mechanisms of pruritogen‐induced activation of itch nerves in isolated mouse skin

Ren

Sun

Jurcakova

et al. 2017

The Journal of Physiology

View full text Add to dashboard Cite

Chloroquine (CQ) and histamine are pruritogens commonly used to study itch in the mouse. A novel skin-nerve preparation was used to evaluate chloroquine (CQ)- and histamine-induced activation of afferent nerves in the dorsal thoracic skin of the mouse. All CQ sensitive nerves were C-fibres, and were also sensitive to histamine. The response to CQ, but not histamine, was largely absent in mrgpr-cluster Δ mice, supporting the hypothesis that CQ evokes itch largely via stimulation of MrgprA3 receptors. The CQ-induced action potential discharge was largely absent in phospholipase Cβ3 knockout animals. The CQ and histamine responses were not influenced by removal of TRPA1, TRPV1, TRPC3 or TRPC6, nor by the TRP channel blocker Ruthenium Red. The bouts of scratching in response to CQ were not different between wild-type and TRPA1-deficient mice. A selective inhibitor of the calcium-activated chloride channel TMEM16A, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid (MONNA), inhibited CQ-induced action potential discharge at itch nerve terminals and bouts of scratching by about 50%. Although TRPA1 and TRPV1 channels may be involved in the scratching responses to intradermal pruritogens, this is unlikely to be due to an effect at the nerve terminals, where chloride channels may play a more important role.

show abstract

Section: Methodsmentioning

confidence: 97%

Mechanisms of pruritogen‐induced activation of itch nerves in isolated mouse skin

Ren

Sun

Jurcakova

et al. 2017

The Journal of Physiology

View full text Add to dashboard Cite

show abstract

“…GCaMP6f) (Chen et al, 2013) would enable us to directly examine the tuning properties of large populations of molecularly defined neurons (Emery et al, 2016; Smith-Edwards et al, 2016; Yarmolinsky et al, 2016) to uncover the existence of subclasses with specialized functions. Here, we use functional in vivo imaging to demonstrate that cutaneous Cacla neurons that project to hairy skin form two distinct groups: polymodal nociceptors and high threshold mechanoreceptors (that we call Circ-HTMRs).…”

Section: Introductionmentioning

confidence: 99%

Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull

Ghitani

Barik

Szczot

et al. 2017

Neuron

107

View full text Add to dashboard Cite

SUMMARY The somatosensory system provides animals with the ability to detect, distinguish and respond to diverse thermal, mechanical and irritating stimuli. While there has been progress in defining classes of neurons underlying temperature sensation and gentle touch, less is known about the neurons specific for mechanical pain. Here, we use in vivo functional imaging to identify a class of cutaneous sensory neurons that are selectively activated by high threshold mechanical stimulation (HTMRs). We show that their optogenetic excitation evokes rapid protective and avoidance behaviors. Unlike other nociceptors, these HTMRs are fast conducting Ad-fibers with highly specialized circumferential endings wrapping the base of individual hair follicles. Notably, we find that Ad-HTMRs innervate unique but overlapping fields and can be activated by stimuli as precise as the pulling of a single hair. Together the distinctive features of this class of Ad-HTMRs appear optimized for accurate and rapid localization of mechanical pain.

show abstract

“…; Emery et al . ). As the fibres innervate each of the laminae differently it is important to record from all laminae to fully understand the network's input at rest and in response to stimulation.…”

Section: Resultsmentioning

confidence: 97%

“…Recently, intra‐vital imaging has been used to quantify population data from the DRG (Emery et al . ; Kim et al . ; Yarmolinsky et al .…”

Section: Introductionmentioning

confidence: 99%

Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

Greenspon

Battell

Devonshire

et al. 2018

The Journal of Physiology

View full text Add to dashboard Cite

Key points Traditional, widely used in vivo electrophysiological techniques for the investigation of spinal processing of somatosensory information fail to account for the diverse functions of each lamina.To overcome this oversimplification, we have used multi‐electrode arrays, in vivo, to simultaneously record neuronal activity across all laminae of the spinal dorsal horn.Multi‐electrode arrays are sensitive enough to detect lamina‐ and region‐specific encoding of different subtypes of afferent fibres and to detect short‐lived changes in synaptic plasticity as measured by the application of cutaneous electrical stimulation of varying intensity and frequency.Differential encoding of innocuous and noxious thermal and mechanical stimuli were also detected across the laminae with the technique, as were the effects of the application of capsaicin.This new approach to the study of the dorsal spinal cord produces significantly more information per experiment, permitting accelerated research whilst also permitting the effects of pharmacological tools to modulate network responses. AbstractThe dorsal horn (DH) of the spinal cord is a complex laminar structure integrating peripheral signals into the central nervous system. Spinal somatosensory processing is commonly measured electrophysiologically in vivo by recording the activity of individual wide‐dynamic‐range neurons in the deep DH and extrapolating their behaviour to all cells in every lamina. This fails to account for the specialized processes that occur in each lamina and the considerable heterogeneity in cellular phenotype within and between laminae. Here we overcome this oversimplification by employing linear multi‐electrode arrays (MEAs) in the DH of anaesthetized rats to simultaneously measure activity across all laminae. The MEAs, comprising 16 channels, were inserted into the lumbar dorsal horn and peripheral neurons activated electrically via transcutaneous electrodes and ethologically with von Frey hairs (vFHs) or an aluminium heating block. Ascending electrical stimuli showed fibre thresholds with distinct dorsoventral innervation profiles. Wind up was observed across the DH during the C‐fibre and post‐discharge latencies following 0.5 Hz stimulation. Intrathecal application of morphine (5 ng/50 μl) significantly reduced Aδ‐ and C‐fibre‐evoked activity in deep and superficial DH. Light vFHs (≤10 g) predominantly activated intermediate and deep laminae whereas noxious vFHs (26 g) also activated the superficial laminae. Noxious heat (55°C) induced significantly greater activity in the superficial and deep laminae than the innocuous control (30°C). The application of these arrays produced the first description of the processing of innocuous and noxious stimuli throughout the intact DH.

show abstract

In vivo characterization of distinct modality-specific subsets of somatosensory neurons using GCaMP

Abstract: In vivo imaging shows that the great majority of somatosensory neurons are modality-specific.

Cited by 102 publications

References 30 publications

Mechanisms of pruritogen‐induced activation of itch nerves in isolated mouse skin

Mechanisms of pruritogen‐induced activation of itch nerves in isolated mouse skin

Specialized Mechanosensory Nociceptors Mediating Rapid Responses to Hair Pull

Lamina‐specific population encoding of cutaneous signals in the spinal dorsal horn using multi‐electrode arrays

Contact Info

Product

Resources

About