Visualizing Remodeling at the Retinogeniculate Synapse

摘要 发育中的中枢神经系统(CNS)中精确突触连接的形成 对神经功能至关重要。在视网膜生成的突触上， 视网膜和丘脑外侧膝状体(LGN)：几个发育阶段 有助于突触神经回路的形成、完善和成熟。在最初的 将神经元映射到其靶点时，轴突会发生大体的形态重排 乔木，因为视网膜神经节细胞(RGC)轴突分离成眼睛特有的层。在老鼠身上， 我们已经发现，在RGC轴突分离到LGN的适当区域后很长时间 (出生后第8天，第8天)，有两个时期的强大突触可塑性和重塑。这个 突触可塑性的第一阶段发生在睁开眼睛的时间(p12-14)，当一些 视网膜到给定LGN中继神经元的输入加强，而其他输入被修剪。一个 第二，以前未检测到的，塑性阶段发生在p20之后，当强度和 视网膜原突触的连通性对感官体验变得敏感。 在这里，我们建议研究视网膜轴突的形态变化 突触可塑性的两个时期。为了做到这一点，我们将利用可用的转基因 并产生新的小鼠品系，在这些品系中，它们的RGC的稀疏子集共同表达 标记轴突乔木和突触前标记突触素的标记，使用不同的 荧光颜色。利用这些小鼠，我们将检查SELECT的形态变化 视网膜神经节细胞轴突与轴突内突触的相对分布 乔木领地。在正常情况下，这些更改将被量化为连接重建 发育，以及在可塑性第二阶段对视觉剥夺的反应。我们 将检验这样一种假设，即RGC轴突杆结构比功能所需的更广泛 并在睁开眼睛的时候变得稳定。我们还将研究这些时期是否 强健的突触可塑性代表着在固定的 Axon Arbor支架。发现了一个广泛的结构支架，在其中可以形成突触接触， 断裂和重排可能代表了一种相对新颖的神经可塑性。通过关联 为了使结构发挥作用，我们希望更清楚地了解 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.