Imaging functional connectivity in visual cortex

视觉皮层功能连接成像

基本信息

批准号：
8917225
负责人：
RAFAEL YUSTE
金额：
$ 38.8万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-01-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8917225
关键词：
Adult Amblyopia Animals Award Biological Models Boxing Brain Calcium Cells Cerebral cortex Classification Computational algorithm Computer Analysis Data Development Functional Imaging Functional disorder Generations Genetic Goals Grant Head Health Image Imaging Techniques Injury Interneurons Knowledge Label Life Light Maps Methods Microscope Mouse Strains Mus Neocortex Neurons Outcome Output Parvalbumins Pattern Photic Stimulation Play Preparation Process Property Pyramidal Cells Research Research Personnel Rest Role Sampling Scanning Slice Somatostatin Structure Synapses Techniques Testing Thalamic structure Time Transgenic Mice Vision Visual Cortex Weight Work area striata awake calcium indicator cell type computer framework design developmental plasticity hippocampal pyramidal neuron in vivo inhibitory neuron neocortical nerve supply neural circuit novel novel strategies novel therapeutics optogenetics photoactivation prevent programs promoter response spatiotemporal two-photon visual information visual plasticity visual process visual processing

项目摘要

DESCRIPTION (provided by applicant): The mammalian visual cortex is necessary for vision and has been used over the decades as a model system for the rest of the cerebral cortex. In spite of this, little is known about its microcircuits, and one could argue that to really understad what the visual cortex does one needs to "open the black box" and decipher them. Moreover, the visual cortex is composed of many different cell types, and, it is likely that each cell type hs a particular circuit function. In the last cycle of the award, using a novel two-photon uncaging technique, we studied the GABAergic interneurons and discovered that two of their major subtypes, PARV and SOM positive cells, are connected in a very dense pattern to cells in their vicinity, often making synaptic connections with every single neighboring neuron. This was surprising since it implies that interneurons connect promiscuously, as if their function was not specific. We now propose to test if this is the case, by examining the input and output connectivity of the four major subtypes of interneurons in V1 (PARV, SOM, VIP and chandeliers). Using two-photon photoactivation with a novel caged compound and a novel channelrhodopsin, and transgenic mouse strains that label subtypes of interneurons specifically, we will map connections to and from interneurons in a systematic fashion, in order to arrive at the inhibitory "circuit blueprint" of mouse V1. In the last aim, using a novel SLM two-photon microscope, we will image the responses of these four subtypes of interneurons in anesthetized and awake animals, under spontaneous activity and visual stimulation. These data will be computationally analyzed to search for spatiotemporal patterns of activity indicative of specific subcircuits. Our work will provide a systematic description of the anatomical and functional connectivity of cortical interneurons, one that will enable to examine whether their function is specific or not and to understand how they regulate the activity of the visual cortex. Given the key role that interneurons appear to play in developmental plasticity, the generated knowledge could also help to understand the pathophysiology of developmental deficits in vision and to design novel therapeutic strategies to treat amblyopia.

描述（由申请人提供）：哺乳动物视觉皮层对于视觉是必需的，并且在数十年中已被用作大脑皮质的其他模型系统。尽管如此，对其微电路的了解知之甚少，人们可以说，要真正将视觉皮层所做的事情理解为“打开黑匣子”并破译它们。此外，视觉皮层由许多不同的细胞类型组成，并且每个单元格类型都可能HS一个特定的电路函数。在该奖项的最后一个周期中，使用一种新型的两光子脉冲技术，我们研究了GABA能中间神经元，发现它们的两个主要亚型PARV和SOM阳性细胞在其附近的细胞中以非常密集的模式连接，通常与每个邻近的神经元建立突触。这是令人惊讶的，因为这意味着中间神经元会混杂连接，好像它们的功能不是特定的。现在，我们建议通过检查V1中神经元的四个主要亚型的输入和输出连接（PARV，SOM，VIP和枝形吊灯）的输入和输出连接。使用新颖的笼化合物和一种新型的通道旋转蛋白以及特殊标记中间神经元亚型的转基因小鼠菌株的两光子光激活，我们将以系统的方式绘制与中间神经元的连接，以便以抑制性“抑制性”电路blueprint到达小鼠V1的抑制性“电路”。在最后一个目标中，使用新型的SLM两光子显微镜，我们将在自发活动和视觉刺激下对麻醉和清醒动物中中间神经元的这四个亚型的反应进行成像。这些数据将进行计算分析，以搜索指示特定亚电路的活动的时空模式。我们的工作将对皮质中间神经元的解剖和功能连通性提供系统的描述，该连通性可以检查其功能是否特定，并了解它们如何调节视觉皮层的活性。鉴于中间神经元在发育可塑性中似乎起着关键作用，因此产生的知识还可以帮助理解视力中发育缺陷的病理生理学，并设计用于治疗弱视的新型治疗策略。