Imaging Inhibitory Processing in the Superior Colliculus

上丘的成像抑制处理

• 批准号: 7028855
• 负责人: WILLIAM Charles HALL
• 金额: $ 15.04万
• 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 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7028855
• 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）：上级丘中间层内的GABA能抑制回路在产生启动注视方向转移的运动前信号中起重要作用。然而，这种抑制的时空动力学仍然不清楚。我们将使用Clomeleon，一种遗传编码的Cl-指示剂，以真实的时间成像Cl-依赖性突触抑制的空间组织。我们已经产生了在中间层的前运动细胞中表达克隆美龙的转基因小鼠。在这些神经元中长期表达的Clomeleon能够响应与GABAA受体活化相关的Cl-通量。我们建议使用这些Clomeleon小鼠，以确定Clomeleon是否足够敏感，以检测[Cl-]i的变化，产生的前运动细胞刺激GABA能通路。为了验证一个假设，即在一个区域中，控制凝视向一个方向转移的前运动细胞的激活抑制了凝视的转移。 在其他区域的细胞的活动，将命令竞争的目光转移到其他方向的刺激，我们将使用Clomeleon可视化的时空分布的抑制整个中间层，这是由一个区域内的活动引起的这一层的空间地图的凝视矢量。这一方法的功能成像CI介导的抑制可能适用于研究抑制回路在任何脑区。