Differential chloride homeostasis in the spinal dorsal horn locally shapes synaptic metaplasticity and modality-specific sensitization

Francesco Ferrini (), Jimena Perez-Sanchez, Samuel Ferland, Louis-Etienne Lorenzo, Antoine G. Godin, Isabel Plasencia-Fernandez, Martin Cottet, Annie Castonguay, Feng Wang, Chiara Salio, Nicolas Doyon, Adalberto Merighi and Yves Koninck
Additional contact information
Francesco Ferrini: University of Turin
Jimena Perez-Sanchez: CERVO Brain Research Centre
Samuel Ferland: CERVO Brain Research Centre
Louis-Etienne Lorenzo: CERVO Brain Research Centre
Antoine G. Godin: CERVO Brain Research Centre
Isabel Plasencia-Fernandez: CERVO Brain Research Centre
Martin Cottet: CERVO Brain Research Centre
Annie Castonguay: CERVO Brain Research Centre
Feng Wang: CERVO Brain Research Centre
Chiara Salio: University of Turin
Nicolas Doyon: CERVO Brain Research Centre
Adalberto Merighi: University of Turin
Yves Koninck: CERVO Brain Research Centre

Nature Communications, 2020, vol. 11, issue 1, 1-18

Abstract: Abstract GABAA/glycine-mediated neuronal inhibition critically depends on intracellular chloride (Cl−) concentration which is mainly regulated by the K+-Cl− co-transporter 2 (KCC2) in the adult central nervous system (CNS). KCC2 heterogeneity thus affects information processing across CNS areas. Here, we uncover a gradient in Cl− extrusion capacity across the superficial dorsal horn (SDH) of the spinal cord (laminae I-II: LI-LII), which remains concealed under low Cl− load. Under high Cl− load or heightened synaptic drive, lower Cl− extrusion is unveiled in LI, as expected from the gradient in KCC2 expression found across the SDH. Blocking TrkB receptors increases KCC2 in LI, pointing to differential constitutive TrkB activation across laminae. Higher Cl− lability in LI results in rapidly collapsing inhibition, and a form of activity-dependent synaptic plasticity expressed as a continuous facilitation of excitatory responses. The higher metaplasticity in LI as compared to LII differentially affects sensitization to thermal and mechanical input. Thus, inconspicuous heterogeneity of Cl− extrusion across laminae critically shapes plasticity for selective nociceptive modalities.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-17824-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17824-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-17824-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().