调节小鼠前脑神经元兴奋性对学习记忆功能的影响作用与机制

At present the Abeta target to improve learning and memory function in Alzheimer's disease research has yet to obtain ideal results, prompted a single target to improve learning and memory function of the limitations, need to find a more effective way to enhance learning and memory function of objective. The study of scientific hypothesis is improved through compensatory neuron excitability especially in learning and memory disorders in the condition may improve or enhance the learning and memory function. In our previous work, using the specific expression of alpha-CamKI driver, successfully obtained a reduced brain voltage-gated KCNQ potassium channel function expression in transgenic mice. A preliminary patch clamp recording shows, the transgenic mice developed normally, hippocampal cortex pyramidal neurons discharge frequency increased and increased excitability. This study tries to combine brain slice electrophysiological recording and integral behavior level, the transgenic mice neurobiological function system assessment, clarify rise forebrain neuronal excitability of mouse learning and memory function of influence. To discuss and confirm the scientific ideas, which strengthen the partly compensatory neuron excitability, for the purpose of improving Alzheimer's disease learning and memory function, provide the experimental basis and new drug development guide.

目前针对Abeta等靶点改善老年痴呆学习与记忆功能的研究尚未取得理想结果，提示单一靶点对改善学习与记忆作用的局限，需要寻找更有效的途径达到增强学习与记忆功能的目的。本研究的科学假设是通过提高代偿性神经元的兴奋性特别是在学习与记忆障碍的条件下，可能会改善或增强学习与记忆的功能。在我们的前期工作中，采用前脑特异表达alpha-CamKI驱动子，成功获得了降低前脑电压门控KCNQ钾通道功能表达的转基因小鼠。初步脑片膜片钳记录表明，该转基因小鼠发育正常、海马皮层锥体神经元放电频率增加和兴奋性增高。本研究拟结合脑片电生理记录和整体行为水平，将对该转基因小鼠的神经生物学功能进行系统的评估，阐明提高前脑神经元的兴奋性对小鼠学习与记忆功能的影响。探讨和证实这一科学设想，对增强部分代偿性神经元兴奋性为目的、改善老年痴呆的学习与记忆的功能，提供实验依据和新药物研发的指导。

目前针对Abeta等靶点改善老年痴呆学习与记忆功能的研究尚未取得理想结果，提示单一靶点对改善学习与记忆作用的局限，需要寻找更有效的途径达到增强学习与记忆功能的目的。本研究的科学假设是通过提高代偿性神经元的兴奋性特别是在学习与记忆障碍的条件下，可能会改善或增强学习与记忆的功能。在我们的前期工作中，采用前脑特异表达alpha-CamKI驱动子，成功获得了降低前脑电压门控KCNQ钾通道功能表达的转基因小鼠。初步脑片膜片钳记录表明，该转基因小鼠发育正常、海马皮层锥体神经元放电频率增加和兴奋性增高。本研究拟结合脑片电生理记录和整体行为水平，将对该转基因小鼠的神经生物学功能进行系统的评估，阐明提高前脑神经元的兴奋性对小鼠学习与记忆功能的影响。探讨和证实这一科学设想，对增强部分代偿性神经元兴奋性为目的、改善老年痴呆的学习与记忆的功能，提供实验依据和新药物研发的指导。