Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex
Effects of the Genetic Depletion of Polysialyltransferases on the Structure and Connectivity of Interneurons in the Adult Prefrontal Cortex
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DOI：
10.3389/fnana.2019.00006
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发表时间：
2019-02-06
影响因子：
2.9
通讯作者：
Nacher, Juan
中科院分区：
文献类型：
--
作者：
Curto, Yasmina;Alcaide, Julia;Nacher, Juan
聚唾液酸（polySia）是一种复杂的糖，在神经系统中主要表现为神经细胞粘附分子（NCAM）的翻译后修饰。PolySia在大脑发育过程中起着重要作用，但在成年期的可塑性中也起着重要作用。两种聚唾液酸转移酶（polyST），ST 8 SIA 2和ST 8 SIA 4，参与polySia的合成和附着。这两个polyST是相关的皮层中间神经元的发育迁移和建立在前额叶皮层（PFC）。相比之下，只有ST 8 SIA 4似乎是重要的结构可塑性的一个亚群的皮质中间神经元在成人。有趣的是，ST 8 SIA 2和NCAM是精神分裂症的候选基因，精神分裂症是一种神经元间回路改变的疾病。然而，仍然没有关于polyST耗尽对树突结构或皮层中间神经元的连接性的影响的数据。在这里，我们研究了每个polyST对这些参数的贡献，在内侧PFC（mPFC）的polyST基因敲除小鼠与GAD 67-GFP标记的中间神经元。ST 8 SIA 4（而不是ST 8 SIA 2）的基因缺失导致中间神经元树枝结构的复杂性降低。相反，消融两种polyST中的任一种诱导锥体神经元上表达体周点的小白蛋白（PV）密度降低。因此，每个polyST的耗尽不仅导致发育迁移，而且还导致中间神经元的传出突触连接的类似损伤。相比之下，ST 8 SIA 4的丢失对树突结构具有独特的影响，因此对传入连接性具有独特的影响，这表明每个polyST对轴突发生和突触发生的差异和独立贡献。
Polysialic acid (polySia) is a complex sugar that in the nervous system appears mainly as a posttranslational modification of the neural cell adhesion molecule (NCAM). PolySia plays important roles during brain development, but also in its plasticity during adulthood. Two polysialyltransferases (polyST), ST8SIA2 and ST8SIA4, are involved in the synthesis and attachment of polySia. Both polyST are relevant for developmental migration of cortical interneurons and their establishment in the prefrontal cortex (PFC). In contrast, only ST8SIA4 appears to be important for the structural plasticity of a subpopulation of cortical interneurons in the adult. Interestingly, ST8SIA2 and NCAM are candidate genes for schizophrenia, a disorder in which interneuronal circuits are altered. However, there is still no data on the effects of polyST depletion on the dendritic structure or the connectivity of cortical interneurons. Here, we studied the contribution of each polyST on these parameters in the medial PFC (mPFC) of polyST knock-out mice with GAD67-GFP-labeled interneurons. Genetic depletion of ST8SIA4, but not ST8SIA2, resulted in a decrease in the complexity of the dendritic arbor of interneurons. In contrast, ablation of either of the two polyST induced a decrease in the density of parvalbumin (PV) expressing perisomatic puncta on pyramidal neurons. Thus, the depletion of each polyST results in similar impairments of not only developmental migration but also efferent synaptic connectivity of interneurons. In contrast, the loss of ST8SIA4 has a unique effect on dendritic structure, hence on afferent connectivity, suggesting differential and independent contributions of each polyST to neuritogenesis and synaptogenesis.