Characterization of Slow AHP conductance in the Developing Mammalian Retina

描述(申请人提供)：自发活动是发育中的哺乳动物神经系统的共同特征。在视觉系统发育之前，邻近的视网膜神经节细胞是视网膜的输出神经元，发出自发的相关动作电位脉冲，随后是一段大约1分钟的静默期。这种在视网膜上传播的活动被称为“视网膜波”。视网膜波是改善神经节细胞与大脑视觉中心的适当突触连接所必需的。自发活动是如何产生的，大约是每分钟一次？我们将结合分子生物学、成像和电生理学来研究这个问题，以研究这种周期性自发活动的细胞机制。具体地说，我们将研究动态水平的cAMP在调节决定波频率的缓慢超极化电导中的作用。拟议中的实验将帮助我们了解大脑发育所必需的活动基础。从这项研究中获得的知识可能有助于我们解释神经系统的紊乱，并可能为修复受损大脑的方法提供基础。

DESCRIPTION (provided by applicant): Spontaneous activity is a common feature in the developing mammalian nervous system. During the development of the visual system prior to vision, neighboring retinal ganglion cells, the output neurons of the retina, fire spontaneous correlated bursts of action potentials followed by a period of silence lasting roughly 1 minute. This activity that propagates across the retina is termed "retinal waves." Retinal waves are required for the refinement of appropriate synaptic connections of ganglion cells to visual centers of the brain. How is spontaneous activity generated on the order of once per minute? We will investigate this question using a combination of molecular biology, imaging, and electrophysiology to study the cellular mechanisms that underlie the properties of this periodic spontaneous activity. Specifically, we will investigate the role of dynamic levels of cAMP in regulating a slow afterhyperpolarizing conductance that determines wave frequency. The proposed experiments will help us understand the basis for activity that is necessary for the development of the brain. Knowledge gained from this research may help us explain disorders of the nervous system and could provide a foundation for means of repairing the injured brain.