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Three neurotransmitters regulate diverse inhibitory and excitatory Parvalbumin interneuron circuits in the dorsal horn

MA Gradwell, KA Boyle, TJ Browne, AC Dickie, AM Bell, J Leonardo, FS Peralta Reyes, KM Smith, RJ Callister, CV Dayas, DI Hughes, BA Graham
doi: https://doi.org/10.1101/2020.12.23.424233
MA Gradwell
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
2Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; and W.M. Keck Center for Collaborative Neuroscience, Rutgers, The State University of New Jersey, Piscataway, NJ, USA
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KA Boyle
3Institute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
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TJ Browne
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
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AC Dickie
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
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AM Bell
3Institute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
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J Leonardo
3Institute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
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FS Peralta Reyes
3Institute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
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KM Smith
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
4Department of Neurobiology and the Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213, USA
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RJ Callister
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
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CV Dayas
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
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DI Hughes
3Institute of Neuroscience Psychology, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK
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  • For correspondence: Brett.Graham@newcastle.edu.au David.I.Hughes@glasgow.ac.uk
BA Graham
1School of Biomedical Sciences & Pharmacy, Faculty of Health, University of Newcastle, Callaghan; and Hunter Medical Research Institute (HMRI), New Lambton Heights, NSW, Australia
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  • For correspondence: Brett.Graham@newcastle.edu.au David.I.Hughes@glasgow.ac.uk
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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 in segregating innocuous tactile input from pain-processing circuits, achieved 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 contributes to the development of mechanical hypersensitivity.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding: This work was funded by the National Health and Medical Research Council (NHMRC) of Australia (grants 631000, 1043933, 1144638, and 1184974 to B.A.G and R.J.C.), the Hunter Medical Research Institute (grant to B.A.G. and R.J.C.), and the BBSRC (grants BB/J000620/1 and BB/P007996/1to D.I.H.).

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted December 24, 2020.
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Three neurotransmitters regulate diverse inhibitory and excitatory Parvalbumin interneuron circuits in the dorsal horn
MA Gradwell, KA Boyle, TJ Browne, AC Dickie, AM Bell, J Leonardo, FS Peralta Reyes, KM Smith, RJ Callister, CV Dayas, DI Hughes, BA Graham
bioRxiv 2020.12.23.424233; doi: https://doi.org/10.1101/2020.12.23.424233
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Three neurotransmitters regulate diverse inhibitory and excitatory Parvalbumin interneuron circuits in the dorsal horn
MA Gradwell, KA Boyle, TJ Browne, AC Dickie, AM Bell, J Leonardo, FS Peralta Reyes, KM Smith, RJ Callister, CV Dayas, DI Hughes, BA Graham
bioRxiv 2020.12.23.424233; doi: https://doi.org/10.1101/2020.12.23.424233

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