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Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold

Albisetti, Gioele W; Ganley, Robert P; Pietrafesa, Francesca; Werynska, Karolina; Magalhaes de Sousa, Marília; Sipione, Rebecca; Scheurer, Louis; Bösl, Michael R; Pelczar, Pawel; Wildner, Hendrik; Zeilhofer, Hanns Ulrich (2023). Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold. Neuron, 111(1):92-105.e5.

Abstract

Proper sensing of ambient temperature is of utmost importance for the survival of euthermic animals, including humans. While considerable progress has been made in our understanding of temperature sensors and transduction mechanisms, the higher-order neural circuits processing such information are still only incompletely understood. Using intersectional genetics in combination with circuit tracing and functional neuron manipulation, we identified Kcnip2-expressing inhibitory (Kcnip2GlyT2) interneurons of the mouse spinal dorsal horn as critical elements of a neural circuit that tunes sensitivity to cold. Diphtheria toxin-mediated ablation of these neurons increased cold sensitivity without affecting responses to other somatosensory modalities, while their chemogenetic activation reduced cold and also heat sensitivity. We also show that Kcnip2GlyT2 neurons become activated preferentially upon exposure to cold temperatures and subsequently inhibit spinal nociceptive output neurons that project to the lateral parabrachial nucleus. Our results thus identify a hitherto unknown spinal circuit that tunes cold sensitivity.

Keywords: circuit; cold; cold allodynia; cold analgesia; cooling; dre recombinase; interneuron; intersectional gene targeting; kcnip2; pain

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 January 2023
Deposited On:15 Nov 2022 14:46
Last Modified:28 Jan 2025 02:35
Publisher:Cell Press (Elsevier)
ISSN:0896-6273
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.neuron.2022.10.008
PubMed ID:36323322
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