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Cited by 151Pain Mechanisms and TreatmentsNeuroscience and Neuropharmacology ResearchIon Channels and Receptors

Morphological, neurochemical and electrophysiological features of parvalbumin‐expressing cells: a likely source of axo‐axonic inputs in the mouse spinal dorsal horn

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Hughes, D. I., Sikander, S., Kinnon, C. M., Boyle, K. A., Watanabe, M., Callister, R. J., Graham, B. A.·2012·The Journal of Physiology
DOI 10.1113/jphysiol.2012.235655PMC PMC3476641
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Abstract

Key points: Perception of normal bodily sensations relies on the precise regulation of sensory information entering the dorsal horn of the spinal cord. Inhibitory, axoaxonic, synapses provide a mechanism for this regulation, but the source of these important inhibitory connections remains to be elucidated. This study shows that a subpopulation of spinal interneurons that expresses parvalbumin and have specific morphological, connectivity and functional characteristics are a likely source of the inhibitory inputs that selectivity regulate non‐noxious tactile input in the spinal cord. Our findings suggest that a loss of normal function in parvalbumin positive dorsal horn neurons may result in the development of tactile allodynia, where non‐painful stimuli gain the capacity to evoke the sensation of pain. Abstract Axo‐axonic synapses on the central terminals of primary afferent fibres modulate sensory input and are the anatomical correlate of presynaptic inhibition. Although several classes of primary afferents are under such inhibitory control, the origin of these presynaptic inputs in the dorsal horn is unknown. Here, we characterize the neurochemical, anatomical and electrophysiological properties of parvalbumin (PV)‐expressing cells in wild‐type and transgenic mice where enhanced green fluorescent protein (eGFP) is expressed under the PV promoter. We show that most PV cells have either islet or central cell‐like morphology, receive inputs from myelinated primary afferent fibres and are concentrated in laminae II inner and III. We also show that inhibitory PV terminals in lamina II inner selectively target the central terminals of myelinated afferents (∼80% of 935 PVeGFP boutons) and form axo‐axonic synapses (∼75% of 71 synapses from PV boutons). Targeted whole‐cell patch‐clamp recordings from PVeGFP positive cells in laminae II and III showed action potential discharge was restricted to the tonic firing and initial bursting patterns (67% and 33% respectively; n= 18), and virtually all express Ih subthreshold voltage‐gated currents (94%; n= 18). These neurons show higher rheobase current than non‐eGFP cells but respond with high frequency action potential discharge upon activation. Together, our findings show that PV neurons in laminae II and III are a likely source of inhibitory presynaptic input on to myelinated primary afferents. Consequently PV cells are ideally placed to play an important role in the development of central sensitization and tactile allodynia.

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  • The Cdh3 dorsal inhibitory family comprised Inhib-6, Inhib-7, and Inhib-8 and are likely involved in dampening of dynamic touch and mechanical allodynia.

    “The Cdh3 dorsal, inhibitory family was comprised of Inhib-6, Inhib-7, and Inhib-8 and are likely to be involved in the dampening of dynamic touch and therefore in mechanical allodynia70–72.”

    From A harmonized atlas of mouse spinal cord cell types and their spatial organization (2021) · cites this paper as [71]

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  1. Sokal R, Rohlf F. Biometry: The Principles and Practice of Statistics in Biological Research. New York: W. H. Freeman; 1995. [Google Scholar]

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Authors
Hughes, D. I., Sikander, S., Kinnon, C. M., Boyle, K. A., Watanabe, M., Callister, R. J., & Graham, B. A.
Affiliations
  • University of Newcastle Australia (AU)
  • University of Glasgow (GB)
  • Hokkaido University (JP)
  • Hunter Medical Research Institute (AU)
Corresponding author
  • Hughes, D. I.
  • Graham, B. A.
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2012-08
Volume
590
Issue
16
Pages
3927-3951
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1113/jphysiol.2012.235655
PMC
PMC3476641
OpenAlex
W1723694197
Cited by
151
References
96
Citations by year
2026: 4 · 2025: 9 · 2024: 9 · 2023: 9 · 2022: 19 · 2021: 14 · 2020: 15 · 2019: 6 · 2018: 14 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 15 · 2013: 10
FWCI
7.72
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 29 d)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion)
Funders
  • Biotechnology and Biological Sciences Research Council (BB/J000620/1)
  • Japan Society for the Promotion of Science (24220007)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords
parvalbumin, axo-axonic synapses, dorsal horn, spinal interneurons, presynaptic inhibition, mechanical allodynia, rheobase, lamina II, lamina III, tactile perception, inhibitory interneurons, EGFP transgenic mice, action potential firing patterns
MeSH terms
Action Potentials, Animals, Antibodies, Axons, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Inbred ICR, Mice, Transgenic, Parvalbumins, Ultraviolet Rays, Patch-Clamp Techniques, Muscle Fibers, Fast-Twitch, Posterior Horn Cells, Green Fluorescent Proteins, Mice, Electrophysiological Phenomena

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