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: 8335400
• 负责人: Richard Todd Pressler
• 金额: $ 4.53万
• 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 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8335400
• 关键词: Area; Arousal; Attention; Automobile Driving; Brain; Brain region; Calcium; Cell Nucleus; Cell physiology; Cells; Defect; Dendrites; Eye; Glutamates; Goals; Hippocampus (Brain); Interneurons; Laboratories; Lateral; Lateral Geniculate Body; Light; Mediating; Membrane Potentials; Metabotropic Glutamate Receptors; Muscarinic Acetylcholine Receptor; Muscarinics; Nervous system structure; Neuromodulator; Neurons; Neurosciences; Optic tract structure; Output; Pathology; Pathway interactions; Pattern; Presynaptic Terminals; Process; Property; Regulation; Research; Rest; Retina; Retinal Ganglion Cells; Role; Route; Sensory Process; Shapes; Site; Stimulus; Sum; Synapses; System; Thalamic structure; Time; Training; Vision; Visual; Visual Cortex; Wakefulness; Work; cholinergic; flexibility; gamma-Aminobutyric Acid; interest; neuroregulation; neurotransmitter release; research study; response; visual information

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.

丘脑在处理感觉信息、将其传递到关键皮质部位以及调节觉醒和觉醒方面发挥着关键作用。丘脑的外侧膝状核（LGN）是人们最感兴趣的，因为它是负责调节从视网膜到视觉皮层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，使它们能够从树突和轴突末端释放神经递质。这些细胞固有的电生理特性使它们能够利用这些特化，在确定丘脑皮质 (TC) 细胞（LGN 的主要输出细胞）抑制的空间和时间特性方面具有极大的灵活性。目前，人们对神经调节剂，尤其是代谢型谷氨酸受体 (mGluR) 如何与这些内在特性相互作用以形成对 TC 细胞的抑制作用还知之甚少。该提案定义了一个行动方案，以确定 mGluR 介导的这种抑制调节的作用。首先，将量化 mGluR 激活对 TC 细胞自发抑制和诱发抑制的影响。我们将探索由于单一输入、输入序列和生理相关输入模式对这种抑制的调节。我们还将确定哪些其他主动电导有助于这种调制。接下来，将定义 LGN 中间神经元中 mGluR 激活的影响，以及中间神经元输出状态和对 TC 细胞引起的抑制之间的关系。我们将探索造成这种变化的机制，其中最主要的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 mGluR 激活引起的调节与另一种神经调节系统——毒蕈碱胆碱能调节的作用联系起来。我们将定义这两种不同的神经调节剂如何协同工作来控制中间神经元输出。