Homotypic Regulation of Neuronal Morphology and Connectivity in the Mouse Retina

Homotypic Regulation of Neuronal Morphology and Connectivity in the Mouse Retina
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DOI:
10.1523/jneurosci.2844-11.2011
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发表时间:
2011-10-05
影响因子:
5.3
通讯作者:
Reese, Benjamin E.
Reese, Benjamin E.
中科院分区:
医学1区
文献类型:
--
作者:
Lee, Sammy C. S.;Cowgill, Erin J.;Reese, Benjamin E.

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发育过程中神经元回路的建立依赖于指定神经元形式的细胞内在机制的作用,以及需要在传入和目标之间传递神经活动的塑性过程。在这里,我们研究了小鼠视网膜内邻近样细胞之间的相互作用在神经元分化和电路形成中的作用。使用两种不同的转基因小鼠模型来调节同型邻居(7型锥体双极细胞)的密度,而不影响其传入细胞(锥体光感受器)的密度。我们发现,当7型锥体双极细胞的密度升高或降低时,树突场区域具有相应的可塑性。在一个不变的传入事件群体中,与树突场面积的变化一致,单个7型锥体双极细胞也显示出在不改变每个锥体蒂接触数量的情况下调节接触的锥体蒂的数量。对发育中的7型锥体双极细胞的分析表明,成熟期的树突平铺是在树突重叠的初始阶段之后次要实现的,此时树突终末在锥体蒂的水平上分层,但不局限于它们。这些结果表明,神经回路形成具有明显的发育可塑性,独立于神经活动,需要邻近细胞之间的同型相互作用,最终调节视网膜内的连通性。
The establishment of neuronal circuitry during development relies upon the action of cell-intrinsic mechanisms that specify neuronal form as well as plastic processes that require the transmission of neural activity between afferents and their targets. Here, we examine the role of interactions between neighboring like-type cells within the mouse retina upon neuronal differentiation and circuit formation. Two different genetically modified mouse models were used to modulate the density of homotypic neighbors, the Type 7 cone bipolar cells, without affecting the density of their afferents, the cone photoreceptors. We demonstrate a corresponding plasticity in dendritic field area when the density of Type 7 cone bipolar cells is elevated or reduced. In accord with this variation in dendritic field area across an invariant population of afferents, individual Type 7 cone bipolar cells are also shown to modulate the number of cone pedicles contacted without varying the number of contacts at each cone pedicle. Analysis of developing Type 7 cone bipolar cells reveals that the dendritic tiling present in maturity is achieved secondarily, after an initial stage of dendritic overlap, when the dendritic terminals are stratified at the level of the cone pedicles but are not localized to them. These results demonstrate a conspicuous developmental plasticity in neural circuit formation independent of neural activity, requiring homotypic interactions between neighboring cells that ultimately regulate connectivity within the retina.