Cantallops I, Routtenberg A
Cresap Neuroscience Laboratory, Northwestern Institute for Neuroscience, Northwestern University, Evanston, Illinois 60208, USA.
J Comp Neurol. 1996 Mar 4;366(2):303-19. doi: 10.1002/(SICI)1096-9861(19960304)366:2<303::AID-CNE9>3.0.CO;2-9.
Hippocampal granule cells do not normally express the axonal growth- and plasticity-associated protein F1/GAP-43 in the adult rat. Using three different methods that lead to hypersynchronous activity in limbic circuits, expression of F1/GAP-43 mRNA can be induced in granule cells which is followed by sprouting in mossy fibers, the axons of granule cells. F1/GAP-43 mRNA expression in granule cells was induced in the temporal, but not septal, hippocampus beginning at 12 hours after kainic acid (KA) subcutaneous injection (10 mg/kg). Beginning 2 days after KA treatment, mossy fiber sprouts restricted to the temporal hippocampus were observed in the supragranular layer. In the same animal we also observed that levels of protein F1/GAP-43 immunoreactivity in this layer apparently increased at this same 2 day time point and same ventral hippocampal location. F1/GAP-43 protein levels and mossy fiber sprouting showed an increase up to 10 days after KA treatment. Sprouting was at a maximum at 40 days, the longest time point studied. These events parallel axonal regeneration with one critical difference: granule cell axons are not damaged by kainate. The rapid onset of axonal growth in the adult is striking and occurs earlier than reported previously (2 days vs. 12 days). Such growth closely associated with elevated levels of protein F1/GAP-43 may occur as a result of a) reactive synaptogenesis caused by the availability of post-synaptic surface on granule cell dendrites at the supragranular layer, b) Hebbian co-activation of the post-synaptic granule cells and their presynaptic afferents, and c) loss of target-derived inhibitory growth factor.
在成年大鼠中，海马颗粒细胞通常不表达与轴突生长和可塑性相关的蛋白F1/GAP-43。采用三种不同方法使边缘回路产生超同步活动，可诱导颗粒细胞中F1/GAP-43 mRNA表达，随后苔藓纤维（颗粒细胞的轴突）出现发芽。在皮下注射海藻酸（KA，10 mg/kg）12小时后，颞叶海马而非隔区海马的颗粒细胞中可诱导F1/GAP-43 mRNA表达。KA处理2天后，在颗粒上层观察到局限于颞叶海马的苔藓纤维发芽。在同一动物中，我们还观察到在相同的2天时间点以及相同的腹侧海马位置，该层中F1/GAP-43免疫反应性蛋白水平明显升高。KA处理后10天内，F1/GAP-43蛋白水平和苔藓纤维发芽均增加。在研究的最长时间点40天时，发芽达到最大值。这些事件与轴突再生相似，但有一个关键区别：颗粒细胞轴突未被海藻酸盐损伤。成体轴突生长的快速启动很显著，且比之前报道的时间更早（2天对比12天）。这种与F1/GAP-43蛋白水平升高密切相关的生长可能是由于以下原因：a）颗粒细胞树突在颗粒上层的突触后表面可利用性导致的反应性突触形成；b）突触后颗粒细胞与其突触前传入神经的赫布协同激活；c）靶源性抑制生长因子的丧失。
