Curriculum in Neurobiology, University of North Carolina, Chapel Hill, North Carolina, NC 27599, USA.
Restor Neurol Neurosci. 1996 Jan 1;10(3):135-46. doi: 10.3233/RNN-1996-10302.
Experimentally-induced lesions of the basal forebrain have been used to test the hypothesis that the cholinergic system plays a critical role in learning and memory. In the present study, a basal forebrain infusion of colchicine, a microtubule assembly inhibitor, was used to characterize the relationship between a cholinergic marker and behavioral function. Bilateral infusions were made in the nucleus basalis magnocellularis (NBM) of male Long-Evans rats. At 4 weeks post-lesion, behavioral assessments were made on half of the rats in each group. These rats were sacrificed 1 week later and regional choline acetyltransferase (ChAT) activity was measured. The remaining rats were behaviorally tested 11 weeks post-lesion and sacrificed 12 weeks post-lesion. The brains of additional rats were studied for Nissl-staining, ChAT-, GAD- and metEnk immunoreactivity (IR) and AChE histochemistry. At 5 weeks after colchicine infusion, there was a significant decrease in parietal and frontal cortical ChAT activity, impaired acquisition of a water maze spatial navigation task and decreased passive avoidance cross-over latency. At 12 weeks after colchicine infusion, ChAT activity was decreased in frontal but not parietal cortex; acquisition of the water maze task was not significantly different from vehicle-infused rats, and a significant deficit was observed in passive avoidance latency. ChAT-IR in the NBM showed a significant decrease at both time points, while changes in AChE-stained cortical fibers paralleled the ChAT activity. GAD- and metEnk-IR were decreased but were not different between the two time points. These data show task-specific behavioral recovery associated in time with recovery of regional cholinergic markers.
实验性基底前脑损伤被用来检验这样一个假说，即胆碱能系统在学习和记忆中起着关键作用。在本研究中，使用微管组装抑制剂秋水仙碱对基底前脑进行输注，以表征胆碱能标志物与行为功能之间的关系。雄性长耳大仓鼠的基底核大细胞区（NBM）双侧接受输注。在损伤后 4 周，对每组的一半大鼠进行行为评估。这些大鼠在 1 周后被处死，测量其区域胆碱乙酰转移酶（ChAT）活性。其余大鼠在损伤后 11 周进行行为测试，并在损伤后 12 周处死。对其他大鼠的大脑进行尼氏染色、ChAT、GAD 和 metEnk 免疫反应性（IR）和 AChE 组织化学研究。在秋水仙碱输注后 5 周，顶叶和额叶皮质 ChAT 活性显著降低，水迷宫空间导航任务的获得能力受损，被动回避交叉潜伏期缩短。在秋水仙碱输注后 12 周，ChAT 活性在额叶而不是顶叶皮质中降低；水迷宫任务的获得能力与载体输注大鼠无显著差异，而被动回避潜伏期则存在显著缺陷。在两个时间点，NBM 中的 ChAT-IR 都显著降低，而 AChE 染色皮质纤维的变化与 ChAT 活性平行。GAD 和 metEnk-IR 降低，但在两个时间点之间没有差异。这些数据显示与特定任务相关的行为恢复与区域性胆碱能标志物的恢复有关。
