Department of Neuroscience 0624, University of California at San Diego, La Jolla, CA 92093 (USA).
Restor Neurol Neurosci. 1992 Jan 1;4(6):369-80. doi: 10.3233/RNN-1992-4602.
The present experiments examined whether cholinergic grafts reverse the physiological and behavioral deficits of the damaged hippocampus. Fimbria-fornix lesions were performed in young rats and 3 months later half of the lesioned rats received cholinergic-rich basal forebrain transplants. Eight months after grafting we tested the animals behaviorally in the water maze. Following the behavioral experiments, the animals were implanted with chronic recording and stimulating electrodes and the electrical properties of the hippocampus, including spontaneous EEG, interictal spikes, evoked responses, long-term potentiation, and sensitivity to induced seizures were examined. Grafted rats did not show statistically reliable behavioral recovery (swim latencies, swim path lengths) and their performance was identical to the lesion-only group. Acetylcholinesterase reinnervation of the host hippocampus in grafted animals was similar to intact rats; the grafts also contained numerous parvalbumin-immunoreactive neurons. The most striking physiological change was the significant elevation of seizure threshold in the grafted group, but other physiological parameters did not improve consistently. The findings suggest that the presence of septal tissue grafts and restoration of cholinergic reinnervation in animals with previous subcortical denervation of the hippocampus are not sufficient to restore normal hippocampal electrical patterns or to improve behavioral performance.
本实验研究了胆碱能移植是否能逆转受损海马体的生理和行为缺陷。在年轻大鼠中进行穹窿伞-海马伞切断术，3 个月后，一半的损伤大鼠接受富含胆碱能的基底前脑移植。移植后 8 个月，我们在水迷宫中对动物进行行为测试。在行为实验之后，将动物植入慢性记录和刺激电极，检查海马体的电生理特性，包括自发 EEG、癫痫发作间期棘波、诱发反应、长时程增强和对诱导性癫痫发作的敏感性。移植大鼠在行为上没有表现出统计学上可靠的恢复（游泳潜伏期、游泳路径长度），它们的表现与仅损伤组相同。在移植动物中，宿主海马体的乙酰胆碱酯酶再支配与完整大鼠相似；移植物中还含有大量的钙结合蛋白免疫反应性神经元。最显著的生理变化是移植组癫痫发作阈值显著升高，但其他生理参数没有持续改善。这些发现表明，在先前海马体皮质下去神经支配的动物中，隔组织移植物的存在和胆碱能再支配的恢复不足以恢复正常的海马电模式或改善行为表现。
