Anatomical and functional organization of inter-areal feedback circuits in the visual cortex, and their impact on neuronal responses

视觉皮层区域间反馈回路的解剖和功能组织及其对神经元反应的影响

基本信息

批准号：
10636827
负责人：
Alessandra Angelucci
金额：
$ 43.72万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10636827
关键词：
Affect Algorithms Anatomy Area Attention Attention Deficit Disorder Attentional deficit Automobile Driving Biological Models Brain Cells Cerebral cortex Code Color Complex Defect Development Disease Feedback Foundations Functional disorder Funding Goals Human Investigation Knowledge Label Link Maps Measures Mediating Mental disorders Methods Modeling Motion Neocortex Neurologic Neurons Noise Output Pathway interactions Primates Probability Property Rabies virus Research Role Schizophrenia Shapes Signal Transduction Stimulus Stream Stroke Structure System Target Populations Testing V1 neuron V2 neuron Viral Vision Visual Visual Cortex Visual System Visual attention Visual evoked cortical potential Visuospatial Work area V1 area V2 autism spectrum disorder base brain dysfunction cell type cytochrome c oxidase density design extrastriate visual cortex insight neocortical nervous system disorder nonhuman primate novel optical imaging optogenetics receptive field response segregation sensory cortex spatial integration tool visual stimulus

项目摘要

In the mammalian sensory cortex, hierarchically-organized areas are reciprocally connected via feedforward (FF) and feedback (FB) circuits. FF connections generate the more complex response properties of neurons in higher areas within parallel streams specialized in processing specific stimulus attributes. In contrast, the function of FB connections remains unknown. In the visual cortex, FB has been implicated in top-down phenomena, such as visual attention, prediction, and visual context. However, these roles have remained hypothetical, due to the lack of tools to selectively label, record, and manipulate the activity of FB neurons. As FB circuits are ubiquitous in cortex, and abnormalities in FB connectivity and function in humans have been linked to neurological disorders, such as attention deficits and autism, it is important to understand normal FB connectivity and function in primates. During prior funding, we developed novel viral and optogenetic tools to selectively label FB neurons, trace their inputs and outputs, and record and manipulate their activity in primate cortex. Using these tools, we found that, anatomically, FB connections between visual areas V2 and V1 form parallel pathways, make direct contacts with V1 neurons sending FF projections to V2, and link V2 and V1 neurons preferring similar visual stimulus features. Functionally, we found V2 FB conveys global visuo-spatial information to V1, and controls the receptive field size, surround suppression and response amplitude of V1 cells. In these studies, however, we did not disentangle FB connections related to different layers. Anatomical, functional and theoretical evidence indicates that within each parallel FB pathway there are at least two, and probably more, sets of FB arising from, and terminating in, different layers, likely having distinct organizations and functions. Our goal is to understand the connectivity and computational function of FB connections related to different layers of origin and termination within each FB stream. Using selective labeling of FB neurons, we will determine the differential contribution of FB from different V2 layers to their V1 termination layers. Moreover, using rabies-virus-mediated monosynaptic input tracing (TRIO) combined with optical imaging of V1 and V2 functional maps, we will determine the functional connectivity of, and the V1 cell types targeted by, different laminar-specific FB sets (Aims1,2). Finally, we will optogenetically manipulate the activity of distinct V2 FB sets to determine their differential impact on V1 neurons' spontaneous and visually-evoked responses (Aim3). Impact. This proposal will reveal the anatomy and function of laminar-specific FB circuits between V2 and V1. This information will inform and refine models of FB function, influence the design of artificial systems striving to achieve vision, and provide new insights into the circuit-level bases for neurological disorders that have been linked to abnormal FB connectivity and function (attention disorders, autism).

在哺乳动物的感觉皮层中，分层组织的区域通过前馈（FF）相互连接和反馈（FB）电路。 FF 连接产生更复杂的神经元响应特性并行流中专门处理特定刺激属性的区域。相比之下，函数 FB 连接仍然未知。在视觉皮层中，FB 与自上而下的现象有关，例如如视觉注意力、预测和视觉上下文。然而，由于缺乏选择性标记、记录和操纵 FB 神经元活动的工具。由于 FB 电路无处不在在大脑皮层中，人类 FB 连接和功能的异常与神经系统相关对于注意力缺陷和自闭症等疾病，了解正常的 FB 连接和在灵长类动物中发挥作用。在之前的资助期间，我们开发了新型病毒和光遗传学工具来选择性标记 FB 神经元，追踪它们的输入和输出，并记录和操纵它们在灵长类皮层中的活动。使用这些工具，我们发现，从解剖学上讲，视觉区域 V2 和 V1 之间的 FB 连接形成平行通路，使得与 V1 神经元直接接触，将 FF 投影发送到 V2，并链接 V2 和 V1 神经元更喜欢相似的视觉刺激特征。从功能上讲，我们发现 V2 FB 将全局视觉空间信息传递给 V1，并且控制 V1 细胞的感受野大小、周围抑制和响应幅度。在这些研究中，然而，我们并没有理清与不同层相关的FB连接。解剖学、功能和理论证据表明，在每个平行的 FB 通路中，至少有两个，甚至可能更多， FB 集源自不同层并终止于不同层，可能具有不同的组织和功能。我们的目标是了解与不同应用相关的 FB 连接的连接性和计算功能每个 FB 流内的起始层和终止层。使用 FB 神经元的选择性标记，我们将确定 FB 从不同 V2 层对其 V1 终止层的差异贡献。而且，使用狂犬病病毒介导的单突触输入追踪 (TRIO) 结合 V1 和 V2 的光学成像功能图谱，我们将确定不同的功能连接以及所针对的 V1 细胞类型层流特定 FB 集（目标 1,2）。最后，我们将以光遗传学方式操纵不同 V2 FB 集的活动以确定它们对 V1 神经元自发反应和视觉诱发反应的不同影响 (Aim3)。影响。该提案将揭示 V2 和 V1 之间层流特定 FB 电路的解剖结构和功能。这些信息将告知和完善 FB 功能模型，影响人工系统的设计实现愿景，并为神经系统疾病的电路级基础提供新的见解与异常的 FB 连接和功能（注意力障碍、自闭症）有关。