Casagrande V A, Condo G J
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Neurosci. 1988 Feb;8(2):395-416. doi: 10.1523/JNEUROSCI.08-02-00395.1988.
The main objective of this study was to examine the role of neural activity in the development of cell layers in the dorsal lateral geniculate nucleus (LGN). We studied this relationship in postnatal tree shrews either by completely blocking retinal ganglion cell activity with TTX or by selectively blocking activity to the developing ON-center LGN layers (1 and 2) with 2-amino-4-phosphonobutyric acid (APB), using unilateral and bilateral eye injections. All manipulations were carried out from birth (P0), when no LGN cell layers are evident, to or past the point when layers are recognizable (i.e., 1-2 weeks). Nissl-stained and cytochrome oxidase (CO)-reacted material was examined for all cases. Our results show that in the absence of activity produced by bilateral TTX injections, interlaminar spaces between cell layers do begin to develop. Retinal afferents, which are segregated at birth, remain segregated, and differential CO staining between matched sets of LGN layers is evident. The normal pace of LGN development, however, is slowed significantly: LGN cells are smaller and interlaminar spaces are narrower than are seen in age-matched controls. Unilateral TTX injections produce similar, but more dramatic and asymmetric, effects on LGN cells, perhaps because cells are at a competitive disadvantage relative to their normally innervated counterparts in cortex. Combining unilateral eye enucleation at P0 with subsequent TTX treatment of the other eye clearly demonstrates that axons from the remaining eye are capable of producing their normal complement of LGN layers. The development of the LGN ON-center layers, 1 and 2, and the interlaminar space between them are more affected by TTX treatment than are the other layers. By contrast, APB eye injections do not selectively affect the development of the ON-center layers, but do result in some slowing of overall LGN development. Taken together, these results suggest that activity of retinal afferents is not essential for initiating interlaminar space formation, but is important for the normal pace of maturation of LGN cell layers.
本研究的主要目的是探讨神经活动在背外侧膝状核（LGN）细胞层发育中的作用。我们通过用河豚毒素（TTX）完全阻断视网膜神经节细胞的活动，或用2-氨基-4-磷酸丁酸（APB）选择性阻断发育中的ON中心LGN层（1层和2层）的活动，对出生后的树鼩进行了研究，采用单侧和双侧眼内注射。所有操作均从出生时（P0）开始，此时LGN细胞层不明显，一直持续到或超过细胞层可识别的时间点（即1 - 2周）。对所有病例的尼氏染色和细胞色素氧化酶（CO）反应物质进行了检查。我们的结果表明，在双侧TTX注射导致活动缺失的情况下，细胞层之间的层间间隙确实开始发育。出生时就分离的视网膜传入纤维保持分离状态，并且匹配的LGN层组之间的CO染色差异明显。然而，LGN发育的正常进程显著减慢：LGN细胞比年龄匹配的对照组中的细胞小，层间间隙也更窄。单侧TTX注射对LGN细胞产生类似但更显著且不对称的影响，这可能是因为相对于其在皮质中正常接受神经支配的对应细胞，这些细胞处于竞争劣势。在P0时单侧眼球摘除并随后对另一只眼进行TTX处理，清楚地表明来自剩余眼睛的轴突能够产生其正常的LGN层补充。LGN的ON中心层1层和2层及其之间的层间间隙的发育比其他层更受TTX处理的影响。相比之下，APB眼内注射不会选择性地影响ON中心层的发育，但确实会导致LGN整体发育有所减慢。综上所述，这些结果表明视网膜传入纤维的活动对于启动层间间隙形成并非必不可少，但对于LGN细胞层成熟的正常进程很重要。
