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Interrogation of Eye Movement Circuits using fMRI and Optogenetics

使用功能磁共振成像和光遗传学询问眼动回路

基本信息

批准号：
8776030
负责人：
Michele A Basso
金额：
$ 23.1万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8776030
关键词：
Animals Area Basal Ganglia Behavior Brain Cell Nucleus Cells Cognitive Science Communication Complex Data Electrophysiology (science)Eye Movements Fiber Optics Functional Imaging Functional Magnetic Resonance Imaging Gene Expression Genes Genetic Materials Genetic Techniques Glutamates Goals Imaging Techniques Ion Channel Knowledge Lasers Letters Light Literature Magnetic Resonance Magnetic Resonance Imaging Measures Methods Modeling Molecular Molecular Genetics Monkeys Mus Neurons Neurosciences Output Parvalbumins Pathway interactions Process Proteins Research Rodent Saccades Serotyping Signal Transduction Sorting - Cell Movement Source Structure Substantia nigra structure Techniques Testing Thalamic structure Vasodilation Viral Vector Virus base blood oxygen level dependent cell type cognitive neuroscience gene therapy improved inhibitory neuron innovation meetings neural circuit neuroimaging neuromechanism novel optogenetics promoter public health relevance research study response success superior colliculus Corpora quadrigemina

项目摘要

DESCRIPTION (provided by applicant): In the neuroimaging literature, there is a large gap in knowledge regarding the relationship between blood oxygen level dependent signals (BOLD) that are measured and neuronal inhibition. The circuits in the basal ganglia that control the suppression and release of saccadic eye movements provide a unique opportunity to fill this gap in knowledge. We propose to study BOLD signals in response to activation of an inhibitory circuit involved in eye movement control. We will insert genes encoding the light-activated ion channel, ChR2 into an output nucleus of the basal ganglia causing them to express ChR2. A light source provided to the channel- expressing neurons will open ion channels and cause neuronal depolarization of inhibitory neurons. BOLD signals will be measured. We have one Specific Aim: to determine BOLD signals in response to activation of an inhibitory neural circuit involved in eye movement control. We will perform three experiments to achieve this aim. 1) Using the neuron-specific promoter CAG, we will express ChR2 in neurons of the substantia nigra pars reticulata (nigra) and measure BOLD responses to light activation using fMRI; 2) using inhibitory neuron-specific promoters (PV and GAD67) we will express ChR2 in inhibitory nigral neurons and measure BOLD signals in response to light activation using fMRI; 3) we will record the electrical activity (LFPs) in the super colliculus and the thalamus (targets of nigral inhibition) in response to light activation to compare BOLD responses to electrical responses. The results of these experiments will uncover critical mechanisms of neural processing of inhibition and how this fundamental neuronal activity appears in BOLD signals.

描述（由申请人提供）：在神经影像学文献中，关于测量的血氧水平依赖信号（BOLD）与神经元抑制之间的关系，存在很大的知识缺口。基底神经节中控制跳眼运动抑制和释放的回路为填补这一知识空白提供了一个独特的机会。我们建议研究BOLD信号对参与眼动控制的抑制回路激活的反应。我们将编码光激活离子通道ChR2的基因插入基底神经节的输出核，使它们表达ChR2。向表达通道的神经元提供光源将打开离子通道并引起抑制性神经元的神经元去极化。BOLD信号将被测量。我们有一个特定的目标：确定参与眼动控制的抑制性神经回路激活的BOLD信号。为了达到这个目的，我们将进行三个实验。1)利用神经元特异性启动子CAG，我们将在黑质网状部（黑质）神经元中表达ChR2，并使用fMRI测量BOLD对光激活的反应；2)使用抑制性神经元特异性启动子（PV和GAD67），我们将在抑制性神经元中表达ChR2，并使用fMRI测量光激活响应的BOLD信号；3)我们将记录对光激活反应的上丘和丘脑（黑神经抑制的目标）的电活动（LFPs），以比较BOLD反应和电反应。这些实验的结果将揭示神经处理抑制的关键机制，以及这种基本的神经元活动如何出现在BOLD信号中。