Dynamic Regulation of Feedforward Inhibition in the Visual Thalamus

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）是主要的兴趣，因为它是调节从视网膜到视觉皮层区域的视觉信息流的主要脑区。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。

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.