Project 3 Genetic Analysis of Visual Cortical Plasticity

项目3 视觉皮层可塑性的遗传分析

基本信息

批准号：
7625006
负责人：
MICHAEL P STRYKER
金额：
$ 48.58万
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：
2008
资助国家：
美国
起止时间：
2008-05-19 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7625006
关键词：
Adult Affect Alleles Animal Model Animals Area Awareness Behavioral Biological Assay Cells Cerebral cortex Characteristics Cognition Condition Core Facility Data Collection Defect Dendritic Spines Depth Development Emotional Eye Foxes Genes Genetic Goals Hippocampus (Brain)Image In Vitro Individual Laboratories Learning Lesion Long-Term Potentiation Maps Measures Memory Mental disorders Methods Microelectrodes Molecular Mus Mutant Strains Mice Mutation Neocortex Neuronal Plasticity Neurons Neurosciences Ocular Dominance Pathway interactions Phase Phenotype Pilot Projects Play Prefrontal Cortex Presynaptic Terminals Property Prosencephalon Regulation Research Research Personnel Retrieval Role Series Shapes Signal Transduction Slice Somatosensory Cortex Staging Stimulus Structure Synaptic Transmission Systems Analysis Techniques Testing Thinking Time Tissues Vertebral column Vibrissae Visual Visual Cortex area striata base conditioned fear conditioning critical developmental period day developmental disease experience genetic analysis in vivo innovation monocular monocular deprivation mutant neocortical neural circuit neurobehavioral novel optical imaging programs receptive field research study response somatosensory two-photon visual deprivation

项目摘要

To identify genes required specifically for neocortical plasticity, we will focus on the activity-dependent plasticity of responses to the two eyes in the primary visual cortex during the critical period. We will screen memory mutants selected as likely to be defective in cortical plasticity in Project 1 for deficits in this form of visual cortical plasticity. We will use monocular visual deprivation during the critical period to induce plasticity, and test the mice with microelectrode recordings and intrinsic signal optical imaging methods recently developed in our laboratory. We will then study in detail by the methods noted below mutants that affect plasticity in both somatosensory (Project 2) and visual (this project, Project 3) cortex. Therefore, we will coordinate the sequence of mutant studies in projects 2 and 3 so that mutants that do not affect either visual or somatosensory plasticity can be set aside. The next series of experiments on selected mutant genes will focus on the development of cortical maps and the receptive field properties of individual neurons. Mutations that do not perturb the early development of the cortex and visual responses but do alter cortical plasticity will be the subject of detailed analysis. We will search for the basis of of plasticity defects in the selected mutants by measuring their the effects on the turnover of dendritic spines and synaptic boutons in vivo and the change in this turnover elicited by stimuli that would normally cause plasticity of visual responses. Because the appropriate regulation of intracortical inhibition is known to be a crucial regulator of visual cortical plasticity, we will also determine the effects of selected mutations on inhibitory neurotranmission by making whole cell patch recordings in vitro. These studies will identify novel genetic pathways that are specifically involved in neocortical plasticity. Nearly all of earlier research on genes involved in forebrain plasticity has begun from defects in plasticity in the hippocampus. We are selecting mutants in which hippocampal function should be normal. Defects in neocortical plasticity are likely to underly defects in cognition and awareness that underly many forms of mental illness and neurobehavioral developmental disorders. Identification of genetic pathways in experimental animals will be a first step toward understanding them and formulating rational therapy for these afflictions.

为了识别专门针对新皮质可塑性所需的基因，我们将重点关注活动依赖性在关键时期，对主要视觉皮层中两只眼的反应的可塑性。我们将筛选记忆突变体被选为项目1中的皮质可塑性有缺陷，以这种形式的缺陷视觉皮质可塑性。我们将在关键时期使用单眼视觉剥夺来诱导可塑性，并用微电极记录和内在信号光学成像方法测试小鼠最近在我们的实验室开发。然后，我们将通过下面突变体的方法详细研究影响体感（项目2）和视觉（该项目3）皮质的可塑性。因此，我们将在项目2和3中协调突变研究的序列视觉或体感可塑性可以搁置一旁。关于选定突变体的下一系列实验基因将集中于皮质图的发展和单个神经元的接受场特性。不会扰动皮质和视觉反应的早期发育但会改变皮质的突变可塑性将是详细分析的主题。我们将搜索在通过测量其对树突状刺和突触胸子的营业额的影响来选择突变体体内和这种失误的变化通常会导致视觉的可塑性回答。因为已知对皮质内抑制的适当调节是至关重要的调节剂视觉皮质可塑性，我们还将确定选定突变对抑制性的影响通过在体外制作全细胞斑块记录来进行神经形成。这些研究将确定专门参与新皮质可塑性的新型遗传途径。几乎所有关于涉及前脑可塑性基因的早期研究已经始于可塑性的缺陷海马。我们正在选择海马功能应正常的突变体。缺陷新皮质可塑性可能是在认知和意识中的基本缺陷精神疾病和神经行为的发育障碍。鉴定遗传途径实验动物将是理解它们并制定理性疗法的第一步这些苦难。