Functional state of developing retinogeniculate synapse

描述（由申请人提供）：我们已经开发了视觉系统发育的小鼠模型，其表征了在视网膜神经节细胞轴突与其在丘脑外侧膝状体核（LGN）中的突触后靶之间发生的结构和功能变化。虽然已经描述了视网膜神经轴突图案和连接的许多变化，但仍有许多问题尚未解决。例如，我们对神经元和细胞内信号级联知之甚少，这些神经元和细胞内信号级联决定了为什么某些视网膜输入被保留和加强，而另一些则被削弱并最终被消除。虽然许多连接的诱导性变化依赖于自发的视网膜活动和Hebbian形式的突触可塑性，视觉诱发活动和与维持新重塑连接相关的突触可塑性的作用尚未得到充分探讨。还需要有关视网膜神经突触和LGN中继细胞树突的生长和成熟的详细形态学信息，以充分了解视网膜连接的重塑是如何发生的。本更新的主要目标是：使用电生理学，解剖学和生物化学技术来详细说明L-型Ca ~（2+）通道活动的性质，这是一个在LGN中介导活动依赖性可塑性的重要事件;建立L-型活动和视网膜膝状体连接重塑之间的联系;探索视觉诱发活动的改变如何影响新重建的视网膜膝状体连接的维持;并检查发育中LGN细胞的树突形态，并确定它们的结构-功能关系如何与视网膜轴突的重塑协调。在野生型有色小鼠以及通过靶向缺失23亚基而严重减弱L型Ca 2+通道表达和活性的小鼠中进行研究。发育中的小鼠视网膜神经元通路已成为研究突触连接重塑机制的一个强有力的模型系统。因此，这些研究将提供有关发育中的大脑如何形成精确的连接模式的有价值的信息，并为研究和治疗由异常连接模式形成导致的发育和神经系统疾病提供进一步的见解。公共卫生相关性：这些研究将提供有关发育中的大脑如何形成精确的连接模式的有价值的信息，并为研究和治疗因形成异常连接模式而导致的发育和神经系统疾病提供进一步的见解。

Description (provided by applicant): 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 are: 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 23 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. PUBLIC HEALTH RELEVANCE: 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.