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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：
8415795
负责人：
ADAM RORY MCQUISTON
金额：
$ 35.88万
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/8415795
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.

项目总结