Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn

Gradwell, M. A. et al. (2022) Diversity of inhibitory and excitatory parvalbumin interneuron circuits in the dorsal horn. Pain, 163(3), e432-e452. (doi: 10.1097/j.pain.0000000000002422) (PMID:34326298) (PMCID:PMC8832545)

Abstract

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Boyle, Dr Kieran and Hughes, Dr David I and Bell, Mr Andrew and Dickie, Dr Allen
• Authors: Gradwell, M. A., Boyle, K. A., Browne, T. J., Bell, A. M., Leonardo, J., Peralta Reyes, F. S., Dickie, A. C., Smith, K. M., Callister, R. J., Dayas, C. V., Hughes, D. I., and Graham, B. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience; College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
• Journal Name: Pain
• Publisher: Lippincott, Williams and Wilkins
• ISSN: 0304-3959
• ISSN (Online): 1872-6623
• Published Online: 28 July 2021
• Copyright Holders: Copyright © 2021 International Association for the Study of Pain
• First Published: First published in Pain 163(3): e432-e452
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
174050		Determining the role of calretinin-RorB spinal interneurons in modulating mechanical pain	David I Hughes	Biotechnology and Biological Sciences Research Council (BBSRC)	BB/P007996/1	Institute of Neuroscience & Psychology