Projections and interconnections of genetically defined serotonin neurons in mice.

Projections and interconnections of genetically defined serotonin neurons in mice.
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DOI:
10.1111/j.1460-9568.2011.07936.x
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发表时间:
2012-01
期刊:
The European journal of neuroscience
影响因子:
--
通讯作者:
Commons KG
Commons KG
中科院分区:
其他
文献类型:
--
作者:
Bang SJ;Jensen P;Dymecki SM;Commons KG

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脑5-羟色胺神经元是异质的,可以通过几个解剖学和生理学特征来区分。为了将这种异质性分解为功能相关性的类别,成熟5-羟色胺神经元的亚型先前基于发育期间在后脑的不同菱形(r)段中启动的基因表达差异进行了鉴定。这种基于遗传谱系标准的成熟5-羟色胺神经元亚型的重新定义,沿着使能的遗传命运作图工具,现在允许将各种功能特性(例如轴突投射)分配到这些鉴定的亚型上。此外,我们的方法独特地使不同的5-羟色胺神经元亚型之间的互连被确定,这是特别相关的,因为5-羟色胺神经元的活动是由几个反馈机制。我们使用交叉和减法遗传命运作图工具,以产生三个独立的小鼠品系,其中5-羟色胺神经元出现在不同的菱形节段,无论是r1,r2或r3和r5,唯一区别于所有其他5-羟色胺神经元的增强绿色荧光蛋白的表达。每个亚群的多巴胺能神经元都有一个独特的前脑投射靶点组合。通常一个以上的亚组支配一个单独的目标区域。还观察到不同的5-羟色胺神经元组之间的独特的互连模式,这些通路可以帮助反馈调节回路。总的来说,目前的研究结果表明,激活5-羟色胺神经元的子集可能会导致地形5-羟色胺释放前脑再加上反馈抑制5-羟色胺神经元与替代投射目标。
Brain serotonin neurons are heterogeneous and can be distinguished by several anatomical and physiological characteristics. Toward resolving this heterogeneity into classes of functional relevance, subtypes of mature serotonin neurons were previously identified based on gene expression differences initiated during development in different rhombomeric (r) segments of the hindbrain. This redefinition of mature serotonin neuron subtypes based on the criteria of genetic lineage, along with the enabling genetic fate mapping tools, now allows various functional properties, such as axonal projections, to be allocated onto these identified subtypes. Furthermore, our approach uniquely enables interconnections between the different serotonin neuron subtypes to be determined; this is especially relevant because serotonin neuron activity is regulated by several feedback mechanisms. We used intersectional and subtractive genetic fate mapping tools to generate three independent lines of mice in which serotonin neurons arising in different rhombomeric segments, either r1, r2 or both r3 and r5, were uniquely distinguished from all other serotonin neurons by their expression of enhanced green fluorescent protein. Each of these subgroups of serotonergic neurons had a unique combination of forebrain projection targets. Typically more than one subgroup innervated an individual target area. Unique patterns of interconnections between the different groups of serotonin neurons were also observed and these pathways could subserve feedback regulatory circuits. Overall, the current findings suggest that activation of subsets of serotonin neurons could result in topographic serotonin release in the forebrain coupled with feedback inhibition of serotonin neurons with alternative projection targets.
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