Characterization of Slow AHP conductance in the Developing Mammalian Retina

描述（由申请人提供）：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，视网膜的输出神经元，自发地发出相关的动作电位爆发，随后是一段持续约1分钟的沉默期。这种通过视网膜传播的活动被称为“视网膜波”。视网膜波是完善神经节细胞与大脑视觉中心之间的突触连接所必需的。每分钟一次的自发活动是如何产生的？我们将结合分子生物学、成像和电生理学来研究这种周期性自发活动的细胞机制。具体来说，我们将研究cAMP的动态水平在调节决定波频率的缓慢超极化后电导中的作用。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以帮助我们解释神经系统的紊乱，并可以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.