Cholinergic control of neural network function

项目摘要 这个项目的长期目标是更好地了解 神经递质乙酰胆碱影响大脑皮质原型区域的功能，该区域关键参与了 形成长期记忆。更具体地说，我们感兴趣的是来自一个区域的输入如何 大脑称为Broca的内侧隔/斜角带(释放乙酰胆碱)，影响对 大脑皮质区域(海马区CA1)的输出结构中的神经信息对 形成长期记忆。这些研究将对开发治疗方法具有重要意义。 阿尔茨海默病，可能还有精神分裂症。投射到大脑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，延长存在时间的药物 细胞外间隙中的乙酰胆碱是用于缓解阿尔茨海默氏症症状的治疗方法之一 病人。此外，神经元尼古丁受体功能障碍与某些家族形式的烟碱能受体相关。 精神分裂症。这个五年计划的具体目标是了解乙酰胆碱的释放如何影响 抑制海马区CA1区的中间神经元功能和最终的信息处理。为了做到这一点，我们 会在胆碱能神经元中表达一种名为Head的蛋白质，当 暴露在蓝光下。这将允许我们在活体完整的海马片中诱导乙酰胆碱的释放。 只需向它们闪烁蓝光即可激活CA1。然后我们将研究乙酰胆碱是如何通过 烟碱受体和毒扁豆碱受体的激活都会影响中间神经元的功能，最终影响海马区 CA1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实现这一点 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 治疗阿尔茨海默病和一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.