TRANSPLANTATION OF CHOLINERGIC NEURONS

描述（研究者摘要）：本研究的目的 建议是确定移植胆碱能神经的机制， 神经细胞介导它们的功能效应。 他们假设这些 移植的细胞在功能上被整合到神经回路中， 它们的活性可以通过宿主来源的 光纤输入 他们将通过测定高亲和力来检验这一假设 海马结构中的胆碱摄取（HACU）作为 胆碱能神经细胞和末梢的活动。 在正常动物中 海马体HACU作为空间记忆训练的结果而升高。 他们 预期如果移植的胆碱能神经元接受适当的输入， 那么移植细胞的活性应该 在培训期间也会增加，从而提高 移植物衍生的HACU。 第二个假设是， 多个靶点的胆碱能神经元将更有效地 改善空间记忆缺陷， 单独的目标网站。 他们将通过将胆碱能神经 细胞进入海马结构和压后皮质。 在 正常动物的这两个脑区都接受来自 内侧隔核（MSN）和Broca斜角带区域 （DBB）。 此外，海马、压后皮质或 它们的传入输入导致空间记忆缺陷。 他们期待， 因此，海马内和 胆碱能MSN/DBB细胞的压后内移植物应表现出 增强的空间迷宫性能相比， 单独的海马内或脾内移植物。 第三个目标是确定行为效应是否介导 移植的胆碱能神经元在移植细胞 随后被移除。 这个问题将通过评估 海马内移植海马神经元对大鼠空间记忆能力的影响 胆碱能神经元 移植后行为稳定后 性能，移植的神经元将被选择性地消除， 胆碱能神经毒素AF 64 A 行为表现将是 重新评估以确定移植神经元的丢失是否会 影响空间记忆功能的各个方面。

DESCRIPTION (Investigator's Abstract): The objectives of this research proposal are to determine the mechanisms by which transplanted cholinergic nerve cells mediate their functional effects. They hypothesize that these grafted cells become functionally incorporated into the neural circuitry of the host brain and that their activity can be regulated by host-derived fiber inputs. They will test this hypothesis by determining high affinity choline uptake (HACU) in the hippocampal formation as a measure of the activity of cholinergic nerve cells and terminals. In normal animals hippocampal HACU is elevated as a result of spatial memory training. They anticipate that if grafted cholinergic neurons receive appropriate inputs from the host brain, then the activity of the transplanted cells should also increase during training and thus result in enhanced rates of graft-derived HACU. The second hypothesis is that transplantation of cholinergic neurons at multiple target sites will be more effective in ameliorating spatial memory deficits than transplanting at individual target sites alone. They will test this hypothesis by placing cholinergic cells into both the hippocampal formation and retrosplenial cortex. In normal animals both of these areas of brain receive cholinergic inputs from the region of the medial septal nucleus (MSN) and diagonal band of Broca (DBB). Furthermore, lesions of the hippocampus, retrosplenial cortex, or their afferent inputs result in spatial memory deficits. They expect, therefore, that animals with combined intra-hippocampal and intra-retrosplenial grafts of cholinergic MSN/DBB cells should exhibit enhanced spatial maze performances in comparison to animals with intra-hippocampal or intra-resplenial grafts alone. The third objective is to determine whether the behavioral effects mediated by transplanted cholinergic neurons are sustained when the grafted cells are subsequently removed. This question will be addressed by assessing the spatial memory performance of rats with intrahippocampal grafts of cholinergic neurons. After the stabilization of post-graft behavioral performance, the transplanted neurons will be selectively eliminated using the cholinergic neurotoxin AF64A. Behavioral performance will then be re-evaluated to determine whether the loss of the grafted neurons will affect various aspects of spatial memory function.