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Papers of the Week


Papers: 29 Oct 2022 - 4 Nov 2022


Animal Studies, Pharmacology/Drug Development


2022 Oct 26


Neuron

Editor's Pick

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

Authors

Albisetti GW, Ganley RP, Pietrafesa F, Werynska K, Magalhaes de Sousa M, Sipione R, Scheurer L, Bösl MR, Pelczar P, Wildner H, Zeilhofer H U
Neuron. 2022 Oct 26.
PMID: 36323322.

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 (Kcnip2) 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 Kcnip2 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.