Imaging Inhibitory Processing in the Superior Colliculus

上丘的成像抑制处理

• 批准号: 6769087
• 负责人: WILLIAM Charles HALL
• 金额: $ 15.4万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-15 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6769087
• 关键词: GABA receptor; bioimaging /biomedical imaging; chloride ion; eye movements; fluorescence resonance energy transfer; head movements; laboratory mouse; method development; motor neurons; neural information processing; neural inhibition; neuroanatomy; neurons; photostimulus; reagent /indicator; recombinant proteins; sectioning; superior colliculus; time resolved data; tissue /cell preparation; visual fixation; visual stimulus

DESCRIPTION (provided by applicant): GABAergic inhibitory circuitry within the intermediate layer of the superior colliculus plays an essential role in generating the premotor signals that initiate shifts in the direction of gaze. However, the spatiotemporal dynamics of this inhibition remain unclear. We will use Clomeleon, a genetically-encoded Cl- indicator, to image in real time the spatial organization of Cl- dependent synaptic inhibition. We have produced transgenic mice that express Clomeleon in premotor cells of the intermediate layer. Clomeleon chronically expressed in these neurons is capable of responding to Cl- fluxes associated with activation of GABAA receptors. We propose to use these Clomeleon mice to determine whether Clomeleon is sufficiently sensitive to detect the changes in [Cl-]i that are generated in the premotor cells by stimulation of GABAergic pathways. To test the hypothesis that activation of premotor cells in a region that commands gaze shifts in one direction inhibits the activity of cells in other regions that would command competing gaze shifts toward stimuli in other directions, we will use Clomeleon to visualize the spatiotemporal distribution of inhibition throughout the intermediate layer that is evoked by activity within one region of this layer's spatial map of gaze vectors. This approach of functional imaging CI-mediated inhibition potentially can be applied to the study of inhibitory circuitry in any brain area.

描述（由申请人提供）：上丘中间层内的 GABA 能抑制电路在产生启动注视方向移动的运动前信号方面发挥着重要作用。然而，这种抑制的时空动力学仍不清楚。我们将使用 Clomeleon（一种基因编码的 Cl 指示剂）对 Cl 依赖性突触抑制的空间组织进行实时成像。我们已经培育出在中间层的前运动细胞中表达 Clomeleon 的转基因小鼠。在这些神经元中长期表达的 Clomeleon 能够响应与 GABAA 受体激活相关的 Cl-通量。我们建议使用这些 Clomeleon 小鼠来确定 Clomeleon 是否足够敏感，可以检测通过刺激 GABA 能途径在前运动细胞中产生的 [Cl-]i 变化。为了检验这一假设，即控制目光向一个方向移动的区域中的前运动细胞的激活会抑制 由于其他区域的细胞活动会命令竞争性注视转向其他方向的刺激，我们将使用 Clomeleon 来可视化整个中间层的抑制的时空分布，该抑制是由该层注视向量空间图的一个区域内的活动引起的。这种功能成像 CI 介导的抑制方法可能适用于任何大脑区域的抑制回路的研究。