El-Danaf Rana N, Krahe Thomas E, Dilger Emily K, Bickford Martha E, Fox Michael A, Guido William
Departments of Neuroscience, Neurobiology Section in the Division of Biological Sciences, University of California, San Diego, La Jolla, CA, 92093, USA.
Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, VA, 23298, USA.
Neural Dev. 2015 Jul 15;10:19. doi: 10.1186/s13064-015-0046-6.
The dorsal lateral geniculate nucleus (dLGN) of the mouse has been an important experimental model for understanding thalamic circuit development. The developmental remodeling of retinal projections has been the primary focus, however much less is known about the maturation of their synaptic targets, the relay cells of the dLGN. Here we examined the growth and maturation of relay cells during the first few weeks of life and addressed whether early retinal innervation affects their development. To accomplish this we utilized the math5 null (math5 (-/-) ) mouse, a mutant lacking retinal ganglion cells and central projections.
The absence of retinogeniculate axon innervation led to an overall shrinkage of dLGN and disrupted the pattern of dendritic growth among developing relay cells. 3-D reconstructions of biocytin filled neurons from math5 (-/-) mice showed that in the absence of retinal input relay cells undergo a period of exuberant dendritic growth and branching, followed by branch elimination and an overall attenuation in dendritic field size. However, math5 (-/-) relay cells retained a sufficient degree of complexity and class specificity, as well as their basic membrane properties and spike firing characteristics.
Retinal innervation plays an important trophic role in dLGN development. Additional support perhaps arising from non-retinal innervation and signaling is likely to contribute to the stabilization of their dendritic form and function.
小鼠的背侧外侧膝状体核(dLGN)一直是理解丘脑回路发育的重要实验模型。视网膜投射的发育重塑一直是主要研究重点,然而对于其突触靶标——dLGN的中继细胞的成熟情况却知之甚少。在此,我们研究了出生后最初几周中继细胞的生长和成熟情况,并探讨早期视网膜神经支配是否会影响它们的发育。为实现这一目的,我们利用了math5基因敲除(math5 (-/-))小鼠,这是一种缺乏视网膜神经节细胞和中枢投射的突变体。
视网膜膝状体轴突神经支配的缺失导致dLGN整体萎缩,并扰乱了发育中的中继细胞之间的树突生长模式。对math5 (-/-)小鼠中生物素填充神经元的三维重建显示,在没有视网膜输入的情况下,中继细胞经历了一段树突过度生长和分支的时期,随后是分支消除和树突野大小的整体减小。然而,math5 (-/-)中继细胞保留了足够程度的复杂性和类别特异性,以及它们的基本膜特性和动作电位发放特征。
视网膜神经支配在dLGN发育中起重要的营养作用。可能来自非视网膜神经支配和信号传导的额外支持可能有助于其树突形态和功能的稳定。