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：
8249877
负责人：
MICHAEL P STRYKER
金额：
$ 48.94万
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：
资助国家：
美国
起止时间：
至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8249877
关键词：
Adult Affect Alleles Animal Model Animals Area Awareness Behavioral Biological Assay Cells Cerebral cortex Characteristics Cognition Core Facility Data Collection Defect Dendritic Spines 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 Retrieval Role Series Shapes Signal Transduction Slice Somatosensory Cortex Staging Stimulus Structure Synaptic Transmission Systems Analysis Techniques Testing Time Tissues Vertebral column Vibrissae Visual Visual Cortex area striata base conditioned fear conditioning critical period developmental disease experience genetic analysis imaging modality in vivo innovation monocular monocular deprivation mutant neocortical neural circuit neurobehavioral novel optical imaging 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.

为了确定针对新皮质可塑性所需的基因，我们将重点介绍关键时期对主要视觉皮层中两只眼反应的活性依赖性可塑性。我们将在项目1中以这种视觉皮质可塑性形式的缺陷筛选在项目1中选择有缺陷的记忆突变体。我们将在关键时期使用单眼视觉剥夺来诱导可塑性，并使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，我们将通过下面的方法详细研究，这些方法会影响体感（项目2）和Visual（该项目，项目3）皮质的可塑性。因此，我们将协调项目2和3中突变研究的序列，以便可以将不影响视觉或体感可塑性的突变体搁置一旁。关于选定突变基因的下一系列实验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。我们将通过测量体内的树突状刺和突触胸子的营业额来搜索所选突变体中可塑性缺陷的基础，并在体内以及通常会引起视觉反应可塑性引起的这种失误的变化。由于已知对皮质内抑制的适当调节是视觉皮质可塑性的关键调节剂，因此我们还将确定所选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。几乎所有早期对涉及前脑可塑性基因的研究始于海马可塑性的缺陷。我们正在选择海马功能应正常的突变体。新皮质可塑性的缺陷可能是认知和意识的基本缺陷，这些缺陷是基本的许多形式的精神疾病和神经行为的发育障碍。实验动物中遗传途径的鉴定将是理解它们并为这些苦难制定有理治疗的第一步。