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

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; pai

TRADUÇÃO E ADAPTAÇÃO CULTURAL DO “DIABETES EATING PROBLEM SURVEY – REVISED” PARA O BRASIL

Objective: To translate and culturally adapt the Diabetes Eating Problem Survey – Revised for the Portuguese language of Brazil. Method: Methodological study, with translation, synthesis of translations, back translation, submission to the committee of experts, pre-test and opinion of the original author. It had two translators, two back translators, expert committee and pre-test with 30 people. Results: Through evaluation of a committee of judges and pre-test, evidence of content validity was obtained and adequate semantic analysis was performed. Content validity index higher than 0.90 was obtained. The pre-test showed valid instrument items, easy to understand and answer for the target population. Conclusion: Semantic, idiomatic, conceptual and cultural equivalences of the adapted instrument were achieved, which showed evidence of validity of its content.Objetivo: Traducir y adaptar culturalmente la Encuesta de Problemas de Alimentación de la Diabetes – Revisada para el idioma portugués de Brasil. Método: Estudio metodológico, con traducción, síntesis de traducciones, retrotraducción, presentación al comité de expertos, pre-test y opinión del autor original. Contó con dos traductores, dos traductores traseros, comité de expertos y pre-test con 30 personas. Resultados: A través de la evaluación de un comité de jueces y pre-test, se obtuvieron evidencias de validez de contenido y se realizó un análisis semántico adecuado. Se obtuvo un índice de validez de contenido superior a 0,90. La prueba previa mostró elementos de instrumentos válidos, fáciles de entender y responder para la población objetivo. Conclusión: Se lograron equivalencias semánticas, idiomáticas, conceptuales y culturales del instrumento adaptado, que mostraron evidencia de validez de su contenido.Objetivo: Traduzir e adaptar culturalmente o Diabetes Eating Problem Survey – Revised para a língua portuguesa do Brasil. Método: Estudo metodológico, com tradução, síntese das traduções, retrotradução, submissão a comitê de especialistas, pré-teste e parecer do autor original. Teve dois tradutores, dois retrotradutores, comitê de especialistas e pré-teste com 30 pessoas. Resultados: Mediante avaliação de comitê de juízes e realização do pré-teste, foi alcançada evidência de validade de conteúdo e realizada análise semântica adequada. Obteve-se índice de validade de conteúdo superior a 0,90. O pré-teste mostrou itens do instrumento válidos, fáceis de compreender e responder pela população-alvo. Conclusão: Alcançaram-se equivalências semântica, idiomática, conceitual e cultural do instrumento adaptado, que mostrou evidência de validade de seu conteúdo.

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

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