Bryche Bertrand, Le Bourhis Mikaël, Congar Patrice, Martin Claire, Rampin Olivier, Meunier Nicolas
NBO, INRA, Université Paris-Saclay, 78350, Jouy-en-Josas, France.
UMR 8251 Centre National de la Recherche Scientifique, BFA, Paris Diderot University, Sorbonne Paris Cité University, Paris, France.
Behav Brain Res. 2019 Apr 19;362:1-6. doi: 10.1016/j.bbr.2018.12.048. Epub 2018 Dec 28.
In the olfactory epithelium, olfactory sensitive neurons and their axons are surrounded by glia-like cells called sustentacular cells, which maintain both the structural and ionic integrity of the olfactory mucosa. We have previously found that endothelin-1 (ET-1) can uncouple sustentacular cell gap junctions in vitro similarly as carbenoxolone, a known gap junction uncoupling agent. The role of gap junctions in odorant transduction remains controversial and we explored here if ET-1 naturally produced by the olfactory mucosa could impact odorant detection. Using calcium imaging on olfactory mucosa explant, we first confirmed that ET-1 uncouples gap junctions in an olfactory mucosa preparation preserving the tissue integrity. We next measured the olfactory epithelium responses to odorant stimulation using electro-olfactogram recordings. While the amplitude of the response was not modified by application of ET-1 and carbenoxolone, its repolarizing phase was slower after both treatments. We finally examined the behavioral performances of rat pups in an orientation test based on maternal odor recognition after intranasal instillations of ET-1 or carbenoxolone. While rat pups performances were decreased after ET-1 treatment, it was unchanged after carbenoxolone treatment. Overall, our results indicate that ET-1 modulates olfactory responses at least partly through gap junction uncoupling.
在嗅觉上皮中，嗅觉敏感神经元及其轴突被称为支持细胞的神经胶质样细胞所包围，这些支持细胞维持着嗅觉黏膜的结构和离子完整性。我们之前发现，内皮素-1（ET-1）在体外可使支持细胞间隙连接解偶联，其作用方式与已知的间隙连接解偶联剂羧苄青霉素类似。间隙连接在气味转导中的作用仍存在争议，我们在此探讨嗅觉黏膜自然产生的ET-1是否会影响气味检测。通过对嗅觉黏膜外植体进行钙成像，我们首先证实ET-1在保持组织完整性的嗅觉黏膜制剂中可使间隙连接解偶联。接下来，我们使用嗅觉电图记录来测量嗅觉上皮对气味刺激的反应。虽然应用ET-1和羧苄青霉素后反应的幅度没有改变，但两种处理后其复极化阶段都变慢了。最后，我们在给大鼠幼崽鼻内滴注ET-1或羧苄青霉素后，基于母体气味识别的定向测试中检查了它们的行为表现。虽然ET-1处理后大鼠幼崽的表现下降，但羧苄青霉素处理后其表现未变。总体而言，我们的结果表明ET-1至少部分通过间隙连接解偶联来调节嗅觉反应。
