Functional state of developing retinogeniculate synapse

我们已经开发了一个视觉系统开发的鼠标模型，它的特征是 视网膜神经节细胞轴突和视网膜神经节细胞轴突之间的结构和功能变化 它们的突触后靶点位于丘脑外侧膝状核(LGN)。而当 视网膜原生性轴突图案化和连接性的许多变化 尽管如此，许多问题仍未得到解决。例如，我们对这一领域知之甚少 神经元件和细胞内信号级联决定了为什么某些视网膜 投入被保留和加强，而其他投入被削弱，并最终 被淘汰了。虽然许多连通性的感应性变化依赖于自发的 视网膜活动和Hebbian形式的突触可塑性，视觉诱发的作用 新改建神经元的活动与突触可塑性的维持 这种联系还没有得到充分的探索。详细的形态信息，关于 视黄素原性突触和LGN中继细胞树突的生长和成熟 也需要充分了解视网膜连接的重塑是如何发生的。这个 这次更新的主要目标是使用电生理、解剖学和生化 详细描述L类钙离子通道活动性质的技巧 对调节LGN的活性依赖的可塑性是必不可少的；建立 L型活动与视黄醇原基连接重塑 视觉诱发活动的改变影响新改建的 视网膜原基连接；并观察发育中的树突形态 LGN细胞，并确定其结构-功能关系如何与 视网膜轴突的重塑。研究是在野生型色素沉着的老鼠身上进行的，以及 其中L型钙离子通道表达和活性严重 因靶向缺失3亚基而减弱。发育中的视黄素原酸盐 在小鼠体内的通路已经成为研究 突触连接重塑的潜在机制。因此，这些 研究将提供关于发育中的大脑如何形成精确的 联系的模式，并为研究和治疗提供进一步的洞察力 由于畸形的形成而导致的发育和神经障碍 连接模式。

We have developed a mouse model of visual system development which characterizes the structural and functional changes occurring between retinal ganglion cell axons and their postsynaptic targets in the lateral geniculate nucleus (LGN) of thalamus. While many of the changes in retinogeniculate axon patterning and connectivity have been described, a number of issues remain unresolved. For example we know little about the neural elements and intracellular signaling cascades that govern why certain retinal inputs are preserved and strengthened while others are weakened and eventually eliminated. While many of the inductive changes in connectivity rely on a spontaneous retinal activity and a Hebbian form of synaptic plasticity, the role of visually evoked activity and the synaptic plasticity associated with the maintenance of newly remodeled connections has not been fully explored. Detailed morphological information about the growth and maturation of retinogeniculate synapses and the dendrites of LGN relay cells is also needed to fully appreciate how the remodeling of retinal connections occurs. The major goals of this renewal is to use electrophysiological, anatomical, and biochemical techniques to detail the nature of L-type Ca2+ channel activity an event that appears essential for mediating activity dependent plasticity in LGN; to establish a link between L-type activity and the remodeling of retinogeniculate connections; to explore how alterations in visually evoked activity affect the maintenance of newly remodeled retinogeniculate connections; and to examine the dendritic morphology of developing LGN cells and determine how their structure-function relations are coordinated with the remodeling of retinal axons. Studies are done in wild-type pigmented mice as well as those in which L-type Ca2+ channel expression and activity has been severely attenuated by the targeted deletion of the ¿3 subunit. The developing retinogeniculate pathway in the mouse has emerged as a powerful model system to study the mechanisms underlying the remodeling of synaptic connections. Therefore, these studies will provide valuable information about how the developing brain forms precise patterns of connections and offer further insight into the study and treatment of developmental and neurological disorders that result from the formation of abnormal patterns of connectivity.