Switching retinogeniculate axon laterality leads to normal targeting but abnormal eye-specific segregation that is activity dependent.
Switching retinogeniculate axon laterality leads to normal targeting but abnormal eye-specific segregation that is activity dependent.
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DOI：
10.1523/jneurosci.3462-09.2009
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发表时间：
2009-11-25
期刊：
影响因子：
--
通讯作者：
Mason CA
中科院分区：
文献类型：
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作者：
Rebsam A;Petros TJ;Mason CA
感觉通路的部分交叉允许来自身体两侧的神经输入投射到相同的目标区域，在那里这些信号将被整合。在这里，为了更好地理解眼睛特异性靶向的机制，我们研究了当在视交叉中线交叉时，视网膜神经节细胞（RGC）轴突如何终止于其丘脑靶点，背外侧膝状体核（dLGN）。在EphB 1功能获得和丧失的模型中，EphB 1是指导视交叉处同侧投射的受体，错误路由的RGC靶向相对dLGN中的适当视网膜定位区。然而，在EphB 1-/-小鼠中，错误路由的轴突不与正常投射的RGC轴突混合，而是分离成一个独特的补丁。我们还通过用地棘蛙素阻断相关的活性波进入双眼，重新审视了视网膜活性对眼睛特异性靶向的作用。我们发现，在野生型小鼠，视网膜波是必要的，在出生后第一周的适当分布和眼特异性隔离同侧轴突在成熟的dLGN。此外，在EphB 1-/-小鼠中，同侧轴突的细化在对照条件下受到干扰，并在地棘蛙素治疗后进一步受损。最后，视网膜波需要在EphB 1-/-小鼠中形成错误路由轴突的隔离补丁。这些发现暗示了针对眼睛特异性区域的分子决定因素，这些区域独立于中线引导线索，并且与相关视网膜活动协同作用以塑造视网膜小神经突起。
Partial decussation of sensory pathways allows neural inputs from both sides of the body to project to the same target region where these signals will be integrated. Here, in order to better understand mechanisms of eye-specific targeting, we studied how retinal ganglion cell (RGC) axons terminate in their thalamic target, the dorsal lateral geniculate nucleus (dLGN), when crossing at the optic chiasm midline is altered. In models with gain- and loss-of-function of EphB1, the receptor that directs the ipsilateral projection at the optic chiasm, misrouted RGCs target the appropriate retinotopic zone in the opposite dLGN. However, in EphB1-/- mice, the misrouted axons do not intermingle with normally projecting RGC axons and segregate instead into a distinct patch. We also revisited the role of retinal activity on eye-specific targeting by blocking correlated waves of activity with epibatidine into both eyes. We show that in wild-type mice, retinal waves are necessary during the first postnatal week for both proper distribution and eye-specific segregation of ipsilateral axons in the mature dLGN. Moreover, in EphB1-/- mice, refinement of ipsilateral axons is perturbed in control conditions and is further impaired after epibatidine treatment. Finally, retinal waves are required for the formation of the segregated patch of misrouted axons in EphB1-/- mice. These findings implicate molecular determinants for targeting of eye-specific zones that are independent of midline guidance cues and that function in concert with correlated retinal activity to sculpt retinogeniculate projections.