Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity.
Increased olfactory bulb acetylcholine bi-directionally modulates glomerular odor sensitivity.
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DOI：
10.1038/srep25808
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发表时间：
2016-05-11
影响因子：
4.6
通讯作者：
Fletcher ML
中科院分区：
文献类型：
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作者：
Bendahmane M;Ogg MC;Ennis M;Fletcher ML
嗅球（OB）的肾小球层接受来自Broca斜角带（HDB）水平分支的大量胆碱能输入，并表达毒蕈碱和烟碱乙酰胆碱（ACh）受体。然而，ACh对OB肾小球气味反应的影响仍然未知。使用钙成像转基因小鼠表达的钙指标GCaMP 2在二尖瓣/簇状细胞，我们研究了ACh对肾小球反应增加气味浓度的影响。使用HDB电刺激和体内药理学，我们发现，增加OB ACh导致动态的，活性依赖性的双向调节肾小球气味反应由于毒蕈碱和烟碱激活的组合效应。使用药理学操作，以揭示个人的受体类型的贡献，我们发现，m2毒蕈碱受体激活增加肾小球的敏感性弱的气味输入，而烟碱受体激活降低敏感性强的输入。总的来说，我们发现OB中的ACh增加了肾小球对气味的敏感性并降低了激活阈值。这种效应，沿着对强烈气味输入的响应降低，降低了个体肾小球对增加的浓度的响应强度范围，使得它们在整个浓度范围内更相似。因此，气味表征随着浓度的增加而更加相似。
The glomerular layer of the olfactory bulb (OB) receives heavy cholinergic input from the horizontal limb of the diagonal band of Broca (HDB) and expresses both muscarinic and nicotinic acetylcholine (ACh) receptors. However, the effects of ACh on OB glomerular odor responses remain unknown. Using calcium imaging in transgenic mice expressing the calcium indicator GCaMP2 in the mitral/tufted cells, we investigated the effect of ACh on the glomerular responses to increasing odor concentrations. Using HDB electrical stimulation and in vivo pharmacology, we find that increased OB ACh leads to dynamic, activity-dependent bi-directional modulation of glomerular odor response due to the combinatorial effects of both muscarinic and nicotinic activation. Using pharmacological manipulation to reveal the individual receptor type contributions, we find that m2 muscarinic receptor activation increases glomerular sensitivity to weak odor input whereas nicotinic receptor activation decreases sensitivity to strong input. Overall, we found that ACh in the OB increases glomerular sensitivity to odors and decreases activation thresholds. This effect, along with the decreased responses to strong odor input, reduces the response intensity range of individual glomeruli to increasing concentration making them more similar across the entire concentration range. As a result, odor representations are more similar as concentration increases.