Visualizing Remodeling at the Retinogeniculate Synapse

摘要 在发育中的中枢神经系统（CNS）中形成精确的突触连接 对神经功能至关重要在视网膜膝状体突触处， 视网膜和丘脑外侧膝状体核（LGN），几个发育阶段 有助于合成回路的形成、完善和成熟。在最初的 在神经元与其靶点的映射中，存在轴突的总体形态学重排 乔木，因为视网膜神经节细胞（RGC）轴突分离成眼睛特定的层。在老鼠体内， 我们发现，在长时间后，RGC轴突分离到LGN的适当区域， （出生后第8天，p8），存在两个强大的突触可塑性和重塑时期。的 突触可塑性的第一阶段发生在眼睛睁开的时候（p12-14）， 到给定LGN中继神经元的视网膜输入被加强，而其它输入被修剪。一 第二，以前未检测到的，塑性阶段发生在p20之后，当强度和 视网膜膝状体突触的连接性对感觉体验变得敏感。 在这里，我们建议研究视网膜轴突乔木的形态学变化， 突触可塑性的两个阶段。为此，我们将利用现有的转基因技术， 小鼠，并产生新的小鼠品系，其中它们的RGCs的稀疏子集共表达 标签轴突乔木和突触前标记，突触素，使用不同的 荧光色。使用这些小鼠，我们将研究选择的形态学变化， 视网膜神经节细胞轴突和轴突内突触接触的相对分布 乔木领土。这些变化将被量化为正常期间的连接重构 发育，并在可塑性的第二阶段对视觉剥夺作出反应。我们 我将检验这一假设，即RGC轴突乔木结构更广泛，功能上必要的 并且在眼睛睁开的时间附近变得稳定。我们还将研究这些时期是否 代表突触释放位点在一个固定的 轴突支架发现了一个可以形成突触接触的广泛结构支架， 断裂和重新排列可能代表一种相对新颖类型神经可塑性。由有关的 从结构到功能，我们希望更清楚地了解结构机制， 是突触发育的基础

ABSTRACT The formation of precise synaptic connections in the developing central nervous system (CNS) is critical for neurological function. At the retinogeniculate synapse, the connection between the retina and the lateral geniculate nucleus (LGN) of the thalamus, several developmental phases contribute to the formation, refinement and maturation of synatic circuits. After the initial mapping of a neuron to its target, there is gross morphological rearrangement of the axon arbors, as retinal ganglion cell (RGC) axons segregate into eye-specific layers. In the mouse, we have found that long after RGC axons segregate into the proper region of the LGN (postnatal day 8, p8), there are two periods of robust synaptic plasticity and remodeling. The first phase of synaptic plasticity occurs around the time of eye opening (p12-14) when some of the retinal inputs to a given LGN relay neuron strengthened while other inputs are pruned. A second, previously undetected, phase of plasticity occurs after p20, when the strength and connectivity of the retinogeniculate synapse becomes sensitive to sensory experience. Here we propose to study the morphological changes of retinal axon arbors that correspond to the two periods of synaptic plasticity. To do this, we will take advantage of available transgenic mice, and also generate new mouse lines in which a sparse subset of their RGCs co-express labels that tag axon arbors and the presynaptic marker, synaptophysin, using different fluorescent colors. Using these mice, we will examine changes in the morphology of select retinal ganglion cell axons and the relative distribution of the synaptic contacts within an axon arbor territory. These changes will be quantified as the connection remodels during normal development, and in response to visual deprivation during the second phase of plasticity. We will test the hypothesis that the RGC axon arbor structure is broader that functionally necessary and becomes stable around the time of eye opening. We will also examine whether the periods of robust synaptic plasticity represent rearrangements of synaptic release sites within a fixed axon arbor scaffold. A finding of a broad structural scaffold in which synaptic contacts can form, break and rearrange may represent a relatively novel type of neural plasticity. By relating structure to function, we hope to gain clearer understanding of the structural mechanisms that underlie synaptic development.