Cholinergic control of neural network function

神经网络功能的胆碱能控制

基本信息

批准号：
8264401
负责人：
ADAM RORY MCQUISTON
金额：
$ 37.38万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-13 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8264401
关键词：
Acetylcholine Address Affect Agonist Alzheimer&apos s Disease Area Axon Binding Biological Neural Networks Brain Cells Cholinergic Agonists Cholinergic Fibers Cholinergic Receptors Complex Dendrites Diagonal Band of Broca Diffuse Diffusion Dyes Electric Stimulation Extracellular Space Functional disorder Goals Hippocampus (Brain)Image Individual Injection of therapeutic agent Interneuron function Interneurons Kinetics Life Light Measures Medial Memory Methods Minority Muscarinic Acetylcholine Receptor Muscarinics Neuronal Dysfunction Neurons Neurotransmitter Receptor Neurotransmitters Nicotinic Receptors Output Patients Pharmaceutical Preparations Process Property Proteins Receptor Activation Schizophrenia Slice Stimulus Structure Symptoms Synapses Testing Training Transgenic Mice Variant Viral base cholinergic cholinergic neuron extracellular hippocampal pyramidal neuron information processing interest long term memory neural information processing neuron loss neuronal cell body neurotransmitter release optogenetics patch clamp presynaptic response selective expression synaptic inhibition voltage voltage/patch clamp

项目摘要

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.

项目概要该项目的长期目标是更好地了解如何发布神经递质乙酰胆碱影响大脑原型皮质区域的功能，该区域与长期记忆的形成。更具体地说，我们感兴趣的是来自某个区域的输入如何称为布罗卡内侧隔膜/对角带的大脑（释放乙酰胆碱）影响处理大脑皮层区域（海马 CA1）输出结构中的神经信息，对于长期记忆的形成。这些研究将对开发治疗方法产生重要影响阿尔茨海默病，可能还有精神分裂症。投射到皮质的胆碱能神经元的丧失大脑结构的改变是阿尔茨海默病的一个标志。此外，延长存在时间的药物细胞外空间中的乙酰胆碱是用于缓解阿尔茨海默病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形式的烟碱受体相关。精神分裂症。这个五年项目的具体目标是了解乙酰胆碱释放如何影响抑制性中间神经元功能并最终影响海马 CA1 的信息处理。为此，我们会在胆碱能神经元中表达一种名为 ChIEF 的蛋白质，该蛋白质可以在以下情况下兴奋神经元及其过程：暴露在蓝光下。这将使我们能够在活的完整海马切片中引发乙酰胆碱的释放 CA1 只需在其上闪烁蓝光即可。然后我们将检查乙酰胆碱如何通过烟碱和毒蕈碱受体的激活影响中间神经元功能并最终影响海马 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做到这一点通过全细胞膜片钳方法记录海马 CA1 的活动，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。