Jaubert-Miazza Lisa, Green Erick, Lo Fu-Sun, Bui Kim, Mills Jeremy, Guido William
Department of Cell Biology and Anatomy, Louisiana State Health Sciences Center, New Orleans, LA 70112, USA.
Vis Neurosci. 2005 Sep-Oct;22(5):661-76. doi: 10.1017/S0952523805225154.
The advent of transgenic mice has made the developing retinogeniculate pathway a model system for targeting potential mechanisms that underlie the refinement of sensory connections. However, a detailed characterization of the form and function of this pathway is lacking. Here we use a variety of anatomical and electrophysiological techniques to delineate the structural and functional changes occurring in the lateral geniculate nucleus (LGN) of dorsal thalamus of the C57/BL6 mouse. During the first two postnatal weeks there is an age-related recession in the amount of terminal space occupied by retinal axons arising from the two eyes. During the first postnatal week, crossed and uncrossed axons show substantial overlap throughout most of the LGN. Between the first and second week retinal arbors show significant pruning, so that by the time of natural eye opening (P12-14) segregation is complete and retinal projections are organized into distinct eye-specific domains. During this time of rapid anatomical rearrangement, LGN cells could be readily distinguished using immunocytochemical markers that stain for NMDA receptors, GABA receptors, L-type Ca2+ channels, and the neurofilament protein SMI-32. Moreover, the membrane properties and synaptic responses of developing LGN cells are remarkably stable and resemble those of mature neurons. However, there are some notable developmental changes in synaptic connectivity. At early ages, LGN cells are binocularly responsive and receive input from as many as 11 different retinal ganglion cells. Optic tract stimulation also evokes plateau-like depolarizations that are mediated by the activation of L-type Ca2+ channels. As retinal inputs from the two eyes segregate into nonoverlapping territories, there is a loss of binocular responsiveness, a decrease in retinal convergence, and a reduction in the incidence of plateau potentials. These data serve as a working framework for the assessment of phenotypes of genetically altered strains as well as provide some insight as to the molecular mechanisms underlying the refinement of retinogeniculate connections.
转基因小鼠的出现，使发育中的视网膜膝状体通路成为一个用于研究感觉连接精细化潜在机制的模型系统。然而，目前尚缺乏对该通路形态和功能的详细描述。在此，我们运用多种解剖学和电生理学技术，来描绘C57/BL6小鼠背侧丘脑外侧膝状体核（LGN）中发生的结构和功能变化。在出生后的前两周，来自双眼的视网膜轴突所占据的终末空间量呈现出与年龄相关的减少。在出生后的第一周，交叉和不交叉的轴突在LGN的大部分区域显示出大量重叠。在第一周和第二周之间，视网膜树突出现显著修剪，以至于到自然睁眼时（P12 - 14），分离完成，视网膜投射被组织成不同的眼特异性区域。在这个快速解剖重排的时期，可以使用针对NMDA受体、GABA受体、L型Ca2+通道和神经丝蛋白SMI - 32进行染色的免疫细胞化学标记物，轻松区分LGN细胞。此外，发育中的LGN细胞的膜特性和突触反应非常稳定，类似于成熟神经元。然而，突触连接存在一些显著的发育变化。在早期，LGN细胞对双眼有反应，并接收多达11个不同视网膜神经节细胞的输入。视束刺激还会引发由L型Ca2+通道激活介导的平台样去极化。随着来自双眼的视网膜输入分离到不重叠的区域，双眼反应性丧失，视网膜汇聚减少，平台电位的发生率降低。这些数据为评估基因改变品系的表型提供了一个工作框架，同时也为视网膜膝状体连接精细化的分子机制提供了一些见解。
