Dynamic Properties of Visual Cortical Circuits

描述(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输到大脑的所有信息。根据视觉通路中的位置，这些回路分为两大类。外侧膝状核主要层的局部中间神经元接受来自视网膜的输入，并提供前馈抑制，以传递细胞和彼此。网状结构的周边区由中继细胞支配，并依次向这些细胞反馈抑制。尽管这些抑制网络对视觉很重要，但人们对它们在原位是如何运作的知之甚少。这项拟议的研究通过使用跨学科的方法研究外侧膝状体和外侧膝状体核中的抑制细胞来解决这一差距，该方法将已识别的中间神经元的细胞内记录和细胞外多单位记录与计算分析和建模相结合。目的1)中继性神经元和局部中间神经元的时空感受野如何比较？中继细胞的感受野由同心的ON和OFF亚区构建，具有兴奋和抑制的推挽布局；在那里明亮的刺激被激发，黑暗的刺激被抑制，反之亦然。这种兴奋(PUSH)来自视网膜神经节细胞，其感受场与靶细胞的感受场具有相同的位置和中心标志(开或关)。这一目的验证了一种假设，即抑制(拉动)是通过神经节细胞驱动的中间神经元传递的，这些神经节细胞的视野与目标中继细胞的位置相似，但符号相反。目的2)中继神经元和局部中间神经元是否以相同的方式采样和整合前馈输入？许多丘脑神经元接受来自不止一个神经节细胞的输入。这个目的是问视网膜丘脑会聚是如何重新绘制眼睛中视觉空间的地图的。其他实验探索了以前在中继细胞和中间神经元的解剖学和药理学之间建立的差异如何在突触整合中产生相应的差异。目的3)来自束旁核的反馈抑制是否在多个空间尺度上起作用？人们普遍认为，束旁核调节的是整体活动水平，而不是在视觉加工中扮演空间靶向的角色。然而，越来越多的证据与这种简单的观点背道而驰。这个目的是探索建立网状感受野的回路，并研究这些野的大小范围很大的可能性，甚至在视野中的相同位置。意义：了解健康的大脑是如何运作的，为判断各种疾病引起的变化提供了一个标准，也为测试治疗疾病的药物提供了一个模型系统。因此，了解丘脑抑制回路的正常功能对于确定疾病期间出错的机制是必要的。例如，这个项目直接涉及弱视研究中的一个关键主题，即检查异常视觉体验如何导致中央处理的变化。公共卫生相关性：该项目调查视觉丘脑中的前馈和反馈抑制电路。了解健康大脑中丘脑回路的功能对于识别疾病期间出错的机制是必要的。例如，这里提出的工作直接涉及弱视研究中的一个关键主题，即检查异常视觉体验如何导致中央处理的变化。

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.