Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0709, USA.
J Neurosci. 2011 Jan 12;31(2):575-86. doi: 10.1523/JNEUROSCI.4227-10.2011.
Development of visual system circuitry requires the formation of precise synaptic connections between neurons in the retina and brain. For example, axons from retinal ganglion cells (RGCs) form synapses onto neurons within subnuclei of the lateral geniculate nucleus (LGN) [i.e., the dorsal LGN (dLGN), ventral LGN (vLGN), and intergeniculate leaflet (IGL)]. Distinct classes of RGCs project to these subnuclei: the dLGN is innervated by image-forming RGCs, whereas the vLGN and IGL are innervated by non-image-forming RGCs. To explore potential mechanisms regulating class-specific LGN targeting, we sought to identify differentially expressed targeting molecules in these LGN subnuclei. One candidate targeting molecule enriched in the vLGN and IGL during retinogeniculate circuit formation was the extracellular matrix molecule reelin. Anterograde labeling of RGC axons in mutant mice lacking functional reelin (reln(rl/rl)) revealed reduced patterns of vLGN and IGL innervation and misrouted RGC axons in adjacent non-retino-recipient thalamic nuclei. Using genetic reporter mice, we further demonstrated that mistargeted axons were from non-image-forming, intrinsically photosensitive RGCs (ipRGCs). In contrast to mistargeted ipRGC axons, axons arising from image-forming RGCs and layer VI cortical neurons correctly targeted the dLGN in reln(rl/rl) mutants. Together, these data reveal that reelin is essential for the targeting of LGN subnuclei by functionally distinct classes of RGCs.
视觉系统回路的发育需要视网膜神经元和大脑神经元之间形成精确的突触连接。例如，视网膜神经节细胞（RGC）的轴突在外侧膝状体核（LGN）的亚核内形成突触[即背外侧膝状体核（dLGN）、腹外侧膝状体核（vLGN）和中间膝状体小叶（IGL）]。不同类别的 RGC 投射到这些亚核：dLGN 由成像形成的 RGC 支配，而 vLGN 和 IGL 由非成像形成的 RGC 支配。为了探索调节特定类别的 LGN 靶向的潜在机制，我们试图鉴定这些 LGN 亚核中差异表达的靶向分子。在视放射回路形成过程中，一种在 vLGN 和 IGL 中富集的细胞外基质分子 reelin 是候选靶向分子。在缺乏功能性 reelin（reln(rl/rl)）的突变小鼠中，RGC 轴突的顺行标记显示 vLGN 和 IGL 支配的减少模式和相邻非视网膜接受性丘脑核中转导的 RGC 轴突。使用遗传报告小鼠，我们进一步证明了靶向错误的轴突来自非成像、内源性光敏的 RGC（ipRGC）。与靶向错误的 ipRGC 轴突相反，来自成像 RGC 和第 VI 层皮质神经元的轴突在 reln(rl/rl) 突变体中正确靶向 dLGN。总之，这些数据表明 reelin 对于功能不同的 RGC 类靶向 LGN 亚核是必不可少的。
