TRANSPLANTATION OF CHOLINERGIC NERVE CELLS

含胆碱能神经的胎儿移植研究进展 大鼠隔核的细胞表明，移植的 有能力对海马区结构进行神经支配 受体大鼠。神经再支配的模式似乎相当 特定的和模仿固有间隔产生的图案 传入器。电生理学研究表明， 移植衍生的神经形成功能联系。这 这一概念得到了行为研究的进一步支持 大鼠迷宫学习能力的恢复 隔区组织移植至失神经支配的海马区 队形。这些研究与其他 移植研究导致了神经细胞的拟议使用 干细胞移植在治疗神经功能障碍中的应用 从变性的特定神经元群体中分离出来。 我们建议确定替代来源的胆碱能 外周和中枢神经系统的神经细胞可以 支配海马体结构，形成功能性 关系。睫状神经节、腹侧脊髓和基底核 来自胎鼠的；来自成年的睫状神经节和基底核 大鼠将被移植或作为细胞悬浮液植入 成年大鼠的海马区结构。胆碱能的证据 海马体的神经支配将从 组织化学方法显示乙酰胆碱酯酶和胆碱 乙酰转移酶的定位和从测定法中确定 胆碱乙酰转移酶活性。的功能性质 移植衍生的神经将通过电学方法进行评估 刺激移植并记录诱发反应 在海马体结构内，并通过分析慢- 动物行为举止时的波动活动。行为能力恢复 功能将通过评估T迷宫和水来确定 移植前后大鼠迷宫学习能力的比较。 这些研究将确定替代来源是否 胆碱能神经细胞可支配宿主内的靶部位 正常调节的海马区形成和恢复功能 通过胆碱能隔膜纤维。

Recent studies of fetal transplants containing cholinergic nerve cells of the rat septal nucleus have shown that the transplants have the capacity to innervate the hippocampal formation of recipient rats. The pattern of reinnervation appears to be quite specific and mimics the pattern produced by intrinsic septal afferents. Electrophysiological studies suggest that the transplant-derived innervation forms functional connections. This notion is further supported by behavioral studies that have demonstrated a recovery of maze learning abilities by rats with septal tissue transplanted into the denervated hippocampal formation. These studies in conjunction with other transplantation studies have led to the proposed use of neural transplants in the treatment of neurological disorders that stem from the degeneration specific neuronal populations. We propose to determine whether alternate sources of cholinergic nerve cells from the peripheral and central nervous system can innervate the hippocampal formation and form functional connections. Ciliary ganglia, ventral spinal cord, and basal nuclei from fetal rats; and ciliary ganglia and basal nuclei from adult rats will be grafted or implanted as cell suspensions into the hippocampal formation of adult rats. Evidence for the cholinergic innervation of the hippocampus will be obtained from histochemical methods to reveal acetycholinesterase and choline acetyltransferase localization and from assays to determine choline acetyltransferase activity. The functional nature of the transplant-derived innervation will be assessed by electrically stimulating the transplant and recording the evoked responses within the hippocampal formation, and by analyzing the slow- wave activity in behaving animals. Recovery of behavioral function will be determined by assessing the T-maze and water maze learning abilities of rats with and without transplants. These studies will determine whether alternate sources of cholinergic nerve cells can innervate target sites in the host hippocampal formation and restore functions normally mediated by cholinergic septal fibers.