Dynamic Regulation of Feedforward Inhibition in the Visual Thalamus

视觉丘脑前馈抑制的动态调节

• 批准号: 7913574
• 负责人: Richard Todd Pressler
• 金额: $ 5.22万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7913574
• 关键词: Area; Arousal; Brain; Brain region; Calcium; Cell Nucleus; Cell physiology; Cells; Defect; Dendrites; Eye; Interneurons; Lateral; Lateral Geniculate Body; Light; Mediating; Metabotropic Glutamate Receptors; Muscarinics; Nervous system structure; Neuromodulator; Neurosciences; Output; Pathology; Pattern; Presynaptic Terminals; Process; Property; Regulation; Research; Retina; Role; Route; Sensory Process; Shapes; Site; System; Thalamic structure; Training; Vision; Visual; Visual Cortex; Wakefulness; Work; cholinergic; flexibility; interest; neuroregulation; neurotransmitter release; public health relevance; visual information

DESCRIPTION (provided by applicant): The thalamus performs a critical role in processing sensory information, relaying it to key cortical sites, and regulating arousal and wakefulness. The lateral geniculate nucleus (LGN) of the thalamus is of chief interest, as it is the principal brain area resonisble for regulating visual information flow from the retina to visual cortical areas. Inhibitory interneurons in the LGN have a anatomical specializations enabling them to release neurotransmitter from their dendrites as well as their axon terminals. The intrinsic electrophysiological properties of these cells enables them to take advantage of these specializations for great flexibility in determining the spatial and temporal properties of inhibition onto thalamcortical (TC) cells, the principal output cells of the LGN. Currently, not much is known how neuromodulators, especially metabotropic glutamate receptors (mGluRs) interact with these intrinsic properties to shape inhibition onto TC cells. This proposal defines a course of action to determine the role of mGluR mediated modulation of this inhibition. First, the effect of mGluR activation on spontaneous and evoked inhibition onto TC cells will be quantified. We will explore the modulation of this inhibition due to single inputs, trains of inputs, and physiologically relevant patterns of inputs. We will also determine what other active conductances contribute to this modulation. Next, the effect of mGluR activation in LGN interneurons, and the relationship between interneuron output state and inhibition evoked onto TC cells will be defined. We will explore the mechanisms responsible for this change, chief among them, the altered properties of calcium dynamics associated with this neuromodulatory system. And lastly, we will relate the modulation evoked by mGluR activation to the actions of another neuromodulatory system-- muscarinic cholinergic modulation. We will define how these two different neuromodulators work synergistically to control interneuron output. PUBLIC HEALTH RELEVANCE: This study seeks to elucidate how the lateral geniculate nucleus of the thalamus processes visual information as it is routed from the eye to where it is decoded in higher brain regions. During the course of this research, as I define the parameters of this circuit, I will not only obtain information that may shed light on pathologies associated with vision defects, but I will also enhance our understanding of fundamental processes in neuroscience-- as circuit features found in the lateral genilculate nucleus are also repeated as modules throughout the nervous system. Understanding the mechanisms governing neuromodulation of feedforward inhibition, calcium-dependent regulation of intrinsic cellular physiology, and dynamic state-depedent output will not only help us to understand how visual information is processed in the thalamus, but will also help us to understand how information is processed throughout the brain.

描述（由申请人提供）：丘脑在处理感觉信息、将其传递到关键皮质部位以及调节唤醒和觉醒方面起着关键作用。丘脑的外侧膝状体核（LGN）是主要感兴趣的区域，因为它是调节从视网膜到视觉皮质区域的视觉信息流的主要大脑区域。LGN中的抑制性中间神经元具有解剖学特化，使得它们能够从它们的树突以及它们的轴突终末释放神经递质。这些细胞的内在电生理特性使他们能够利用这些专业化的巨大灵活性，在确定抑制丘脑皮质（TC）细胞，LGN的主要输出细胞的空间和时间特性。目前，尚不清楚神经调节剂，特别是代谢型谷氨酸受体（mGluRs）如何与这些内在特性相互作用，以形成对TC细胞的抑制。该提案定义了一个行动方案，以确定mGluR介导的这种抑制的调节作用。首先，将量化mGluR活化对TC细胞的自发和诱发抑制的影响。我们将探讨这种抑制的调制由于单一的输入，列车的输入，和生理相关的模式的输入。我们还将确定哪些其他有源电导有助于这种调制。接下来，将定义LGN中间神经元中mGluR激活的效果，以及中间神经元输出状态与对TC细胞诱发的抑制之间的关系。我们将探讨负责这种变化的机制，其中主要是与这种神经调节系统相关的钙动力学特性的改变。最后，我们将把mGluR激活引起的调制与另一种神经调节系统--毒蕈碱胆碱能调制的作用联系起来。我们将定义这两种不同的神经调质如何协同控制中间神经元的输出。 公共卫生相关性：本研究旨在阐明丘脑外侧膝状体如何处理视觉信息，因为它是从眼睛路由到更高的大脑区域解码。在这项研究的过程中，当我定义这个回路的参数时，我不仅会获得可能揭示与视力缺陷相关的病理学的信息，而且我还将增强我们对神经科学中基本过程的理解-因为在外侧膝状核中发现的回路特征也作为整个神经系统的模块重复。了解前馈抑制的神经调节机制，钙依赖性的内在细胞生理调节，以及动态状态依赖性的输出不仅有助于我们了解视觉信息在丘脑中是如何处理的，而且还有助于我们了解整个大脑如何处理信息。