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Odour enrichment increases adult-born dopaminergic neurons in the mouse olfactory bulb

机译:气味富集增加小鼠嗅球中成年多巴胺能神经元

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The olfactory bulb (OB) is the first brain region involved in the processing of olfactory information. In adult mice, the OB is highly plastic, undergoing cellular/molecular dynamic changes that are modulated by sensory experience. Odour deprivation induces down-regulation of tyrosine hydroxylase (TH) expression in OB dopaminergic interneurons located in the glomerular layer (GL), resulting in decreased dopamine in the OB. Although the effect of sensory deprivation is well established, little is known about the influence of odour enrichment on dopaminergic cells. Here we report that prolonged odour enrichment on C57BL/6J strain mice selectively increases TH-immunopositive cells in the GL by nearly 20%. Following odour enrichment on TH-green fluorescent protein (GFP) transgenic mice, in which GFP identified both mature TH-positive cells and putative immature dopaminergic cells expressing TH mRNA but not TH protein, we found a similar 20% increase in GFP-expressing cells, with no changes in the ratio between TH-positive and TH-negative cells. These data suggest that enriched conditions induce an expansion in the whole dopaminergic lineage. Accordingly, by using 5-bromo-2-deoxyuridine injections to label adult-generated cells in the GL of TH-GFP mice, we found an increase in the percentage of 5-bromo-2-deoxyuridine-positive dopaminergic cells in enriched compared with control conditions, whereas no differences were found for calretinin- and calbindin-positive subtypes. Strikingly, the fraction of newborn cells among the dopaminergic population doubled in enriched conditions. On the whole, our results demonstrate that odour enrichment drives increased integration of adult-generated dopaminergic cells that could be critical to adapt the OB circuits to the environmental incoming information.
机译:嗅球(OB)是涉及嗅觉信息处理的第一个大脑区域。在成年小鼠中,OB是高度可塑性的,会经历由感官体验调节的细胞/分子动态变化。嗅觉剥夺会诱导位于肾小球层(GL)的OB多巴胺能神经元中酪氨酸羟化酶(TH)表达的下调,从而导致OB中的多巴胺减少。尽管感觉剥夺的作用已被充分确立,但是关于气味富集对多巴胺能细胞的影响知之甚少。在这里,我们报告在C57BL / 6J品系小鼠上延长的气味积累选择性地将GL中的TH免疫阳性细胞增加了近20%。在TH-绿色荧光蛋白(GFP)转基因小鼠上增加气味后,GFP既识别了成熟的TH阳性细胞,又表达了表达TH mRNA但不表达TH蛋白的未成熟多巴胺能细胞,我们发现表达GFP的细胞增加了类似的20% ,TH阳性细胞与TH阴性细胞之间的比例没有变化。这些数据表明,丰富的条件诱导整个多巴胺能谱系的扩展。因此,通过使用5-溴-2-脱氧尿苷注射液标记TH-GFP小鼠GL中成年生成的细胞,我们发现富集的5-溴-2-脱氧尿苷阳性多巴胺能细胞的百分比与对照条件,而钙调蛋白和钙结合蛋白阳性的亚型没有差异。令人惊讶的是,在丰富的条件下,多巴胺能群体中新生细胞的比例增加了一倍。总体而言,我们的研究结果表明,气味富集推动了成年多巴胺能细胞的整合增加,这可能对于使OB电路适应环境传入的信息至关重要。

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