Dynamic Properties of Visual Cortical Circuits

视觉皮层回路的动态特性

• 批准号: 7736685
• 负责人: Judith A Hirsch
• 金额: $ 40.69万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7736685
• 关键词: Address; Amblyopia; Anatomy; Back; Biological Models; Brain; Cell Nucleus; Cells; Computer Analysis; Computer-Assisted Image Analysis; Disease; Event; Eye; Feedback; Feeds; Felis catus; Goals; In Situ; In Vitro; Individual; Interneurons; Knowledge; Lateral Geniculate Body; Learning; Literature; Location; Maps; Methods; Metric; Modeling; Neurons; Pattern; Pharmacology; Pilot Projects; Play; Positioning Attribute; Process; Property; Research; Reticular Cell; Reticular Formation; Retina; Retinal; Retinal Ganglion Cells; Rodent; Role; Route; Sampling; Sensory Process; Shapes; Sorting - Cell Movement; Stimulus; Synapses; Testing; Thalamic structure; Time; Training; Ursidae Family; Vision; Visual; Visual Cortex; Visual Fields; Visual Pathways; Work; base; cell type; drug testing; experience; extracellular; ganglion cell; in vivo; interdisciplinary approach; public health relevance; receptive field; research study; response; spatiotemporal; visual map; visual process; visual processing

Description (provided by applicant): The inhibitory circuits of the visual thalamus dominate local processing and influence all information that relay cells transmit from the eye to the brain. These circuits divide into two major groups based on position in the visual pathway. Local interneurons in the main layers of the lateral geniculate nucleus receive input from the retina and provide feedforward inhibition to relay cells and each other. The perigeniculate sector of the reticular formation is innervated by relay cells and feeds back inhibition to these cells in turn. Despite the importance of these suppressive networks to vision, little is known about how they operate in situ. The proposed research addresses this gap by investigating inhibitory cells in the perigeniculate and lateral geniculate nuclei using an interdisciplinary approach that combines intracellular recording from identified interneurons and extracellular multiunit recording with computational analysis and modeling. Aim 1) How do the spatiotemporal receptive fields of relay cells and local interneurons compare? Relay cells have receptive fields built from concentric On and Off subregions with a push-pull layout of excitation and inhibition; where bright stimuli excite, dark inhibit and vice versa. The excitation (push) comes from retinal ganglion cells whose receptive fields have the same location and center sign (On or Off) as that of the target relay cell. This aim tests the hypothesis that the inhibition (pull) is routed through interneurons driven by ganglion cells whose fields have similar positions but the opposite sign as that of the target relay cell. Aim 2) Do relay cells and local interneurons sample and integrate feedforward input the same way? Many thalamic neurons receive input from more than one ganglion cell. This aim asks how retinothalamic convergence redraws the map of visual space laid out in the eye. Additional experiments explore how previously established disparities between the anatomy and pharmacology of relay cells vs. interneurons produce commensurate differences in synaptic integration. Aim 3) Does feedback inhibition from the perigeniculate nucleus operate over multiple spatial scales? The perigeniculate nucleus is widely believed to regulate global levels of activity rather than to play a spatially targeted role in visual processing. Yet, mounting evidence counters this simple view. This aim explores circuits that build reticular receptive fields and investigates the possibility that these fields range widely in size, even at the same position in the visual field. SIGNIFICANCE: Knowledge of how the healthy brain operates provides a standard against which to judge changes that result from various disorders, as well as a model system for testing drugs developed to treat illness. Thus, understanding how inhibitory circuits in the thalamus normally function is necessary to identify mechanisms that go awry during disease. For example, this project bears directly on a key theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing. PUBLIC HEALTH RELEVANCE: This project investigates feedforward and feedback inhibitory circuits in the visual thalamus. Understanding how thalamic circuits function in the healthy brain is necessary to identify mechanisms that go awry during disease. For example, the work proposed here bears directly on a key theme in research on amblyopia, the examination of how abnormal visual experience leads to changes in central processing.

描述（由申请人提供）：视觉丘脑的抑制回路支配局部处理，并影响中继细胞从眼睛传递到大脑的所有信息。这些回路根据在视觉通路中的位置分为两大类。在外侧膝状体核的主要层中的局部中间神经元接收来自视网膜的输入，并向中继细胞和彼此提供前馈抑制。网状结构的周膝状体部分由中继细胞支配，并依次向这些细胞反馈抑制。尽管这些抑制性网络对视力很重要，但人们对它们在原位的运作方式知之甚少。拟议的研究通过使用跨学科方法研究周膝状体和外侧膝状体核中的抑制性细胞来解决这一差距，该方法将识别的中间神经元的细胞内记录和细胞外多单元记录与计算分析和建模相结合。目的1）中继细胞和局部中间神经元的时空感受野有何异同？中继细胞具有由同心开和关子区域构建的感受野，具有激励和抑制的推拉布局;其中明亮的刺激激发，黑暗抑制，反之亦然。刺激（推动）来自视网膜神经节细胞，其感受野与目标中继细胞具有相同的位置和中心标志（开或关）。这一目的测试的假设，即抑制（拉）是通过神经节细胞驱动的中间神经元，其字段具有类似的位置，但相反的标志作为目标中继细胞。目的2）中继细胞和局部中间神经元以相同的方式对前馈输入进行采样和积分吗？许多丘脑神经元接受来自不止一个神经节细胞的输入。这个目标是询问视网膜丘脑会聚如何重新绘制眼睛中视觉空间的地图。另外的实验探索了先前建立的中继细胞与中间神经元的解剖学和药理学之间的差异如何在突触整合中产生相称的差异。目的3）周膝状体的反馈抑制是否在多个空间尺度上起作用？人们普遍认为，膝状体周围核在视觉处理中调节整体活动水平，而不是发挥空间定位作用。然而，越来越多的证据反驳了这种简单的观点。这个目标探索了建立网状感受野的电路，并调查了这些领域的大小范围很广的可能性，即使在视野中的相同位置。重要性：健康大脑如何运作的知识提供了一个判断各种疾病引起的变化的标准，以及一个测试开发用于治疗疾病的药物的模型系统。因此，了解丘脑中的抑制回路如何正常工作，对于确定疾病期间出错的机制是必要的。例如，这个项目直接关系到弱视研究的一个关键主题，即检查异常的视觉体验如何导致中央处理的变化。公共卫生相关性：该项目研究视觉丘脑中的前馈和反馈抑制回路。了解丘脑回路在健康大脑中的功能对于确定疾病期间出错的机制是必要的。例如，这里提出的工作直接关系到弱视研究的一个关键主题，即检查异常的视觉体验如何导致中央处理的变化。