Cholinergic control of neural network function

项目摘要 本项目的长期目标是更好地理解 神经递质乙酰胆碱影响大脑原型皮质区域的功能，该区域与大脑的功能至关重要。 形成长期记忆。更具体地说，我们感兴趣的是如何从一个领域的投入， 大脑称为内侧隔/Broca对角带，（释放乙酰胆碱），影响大脑的处理， 大脑皮层区域（海马CA 1）输出结构中的神经信息，对大脑的运动至关重要。 形成长期记忆。这些研究将对开发治疗方法具有重要意义。 老年痴呆症可能还有精神分裂症。投射到皮层的胆碱能神经元的丢失 大脑中的结构是阿尔茨海默病的标志。此外，延长存在的药物， 细胞外间隙的乙酰胆碱是用于减轻阿尔茨海默氏症症状的治疗方法之一 患者此外，神经元烟碱受体的功能障碍与某些家族性形式的神经元烟碱受体相关。 精神分裂症这个为期五年的项目的具体目标是了解乙酰胆碱的释放如何影响 抑制中间神经元的功能，并最终在海马CA 1区的信息处理。为此我们 将在胆碱能神经元中表达一种名为ChIEF的蛋白质，这种蛋白质可以刺激神经元及其过程， 暴露在蓝光下。这将使我们能够在海马的完整切片中引起乙酰胆碱的释放。 CA 1只需要在他们身上闪烁蓝光。然后我们将研究乙酰胆碱是如何通过 烟碱和毒蕈碱受体的激活影响中间神经元的功能，并最终影响海马神经元的功能。 CA 1网络功能。我们将通过记录中间神经元和锥体神经元的电反应来做到这一点 通过全细胞膜片钳方法，并通过记录整个网络的活动， 使用电压敏感染料成像。这些研究的结果将对未来的发展产生重要影响。 治疗阿尔茨海默病和某些家族性精神分裂症。

Project Summary The long term goal of this project is to have a better understanding of precisely how the release of the neurotransmitter acetylcholine affects function in a prototypic cortical area of the brain crucially involved in the formation of long term memories. More specifically, we are interested in how the inputs from an area of the brain called the medial septum/diagonal band of Broca, (which releases acetylcholine), affects processing of neural information in an output structure of a cortical area of the brain, (hippocampal CA1), crucial to the formation of long term memories. These studies will have important implications for developing treatments for Alzheimer's disease and possibly schizophrenia. The loss of cholinergic neurons that project to cortical structures in the brain is a hallmark of Alzheimer's disease. Furthermore, drugs that prolong the presence of acetylcholine in the extracellular space are one of the treatments used to alleviate symptoms in Alzheimer's patients. Moreover, dysfunction of neuronal nicotinic receptors has been correlated to some familial forms of schizophrenia. The specific aims for this five year project are to understand how acetylcholine release affects inhibitory interneuron function and ultimately the processing of information in hippocampal CA1. To do this we will express a protein called ChIEF in cholinergic neurons that can excite neurons and its processes when exposed to blue light. This will allow us to elicit the release of acetylcholine in live intact slices of hippocampal CA1 by merely flashing blue light upon them. We will then examine how acetylcholine release through the activation of both nicotinic and muscarinic receptors affects interneuron function and ultimately hippocampal CA1 network function. We will do this by recording electrical responses in interneurons and pyramidal neurons of hippocampal CA1 via whole cell patch clamp methods, and by recording activity in the entire network by using voltage-sensitive dye imaging. The results from these studies will have important implications for the treatment of Alzheimer's disease and some familial forms of schizophrenia.