Imaging Inhibitory Processing in the Superior Colliculus

描述（由申请人提供）：上丘中间层内的gaba能抑制回路在产生启动凝视方向转移的运动前信号中起着至关重要的作用。然而，这种抑制的时空动态尚不清楚。我们将使用Clomeleon，一种基因编码的Cl-指示剂，实时成像Cl-依赖性突触抑制的空间组织。我们培育了在中间层运动前细胞中表达Clomeleon的转基因小鼠。在这些神经元中慢性表达的Clomeleon能够响应与GABAA受体激活相关的Cl-通量。我们打算用这些Clomeleon小鼠来确定Clomeleon是否足够敏感，以检测gaba能通路刺激在运动前细胞中产生的[Cl-]i的变化。为了验证这一假设，即控制凝视方向的前运动细胞的激活会抑制

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.