Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons

Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons
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Neuroligins 差异介导锥体神经元和中间神经元亚型特异性突触形成

DOI:
10.1007/s12264-019-00347-y
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发表时间:
2019-02
影响因子:
5.6
通讯作者:
Xu Junyu
Xu Junyu
中科院分区:
医学2区
文献类型:
--
作者:
Xia Qiang Qiang;Xu Jing;Liao Tai Lin;Yu Jie;Shi Lei;Xia Jun;Luo Jian Hong;Xu Junyu

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神经连接蛋白(NLS)是突触后细胞黏附蛋白,在突触形成和兴奋性-抑制性平衡中发挥重要作用。在人类遗传和动物模型研究中,它们都与自闭症有关,并影响大脑几个区域的突触连接和突触可塑性。然而,目前的研究主要集中在锥体神经元,而NLS在中间神经元中的功能尚不清楚。为了探讨NLS在锥体神经元和中间神经元亚型特异性突触形成中的功能差异,我们在培养的大鼠皮质神经元上进行了病毒介导的NLS的shRNA敲除,并检测了这两种主要类型神经元中的突触。结果表明,NL1和NL3参与兴奋性突触的形成,NL2参与GABA能突触的形成。有趣的是,NL1比NL3更特异地影响GABA能突触的形成,而NL2优先影响锥体神经元的兴奋性突触密度。综上所述,我们的结果表明,不同的NLS在调节锥体神经元和中间神经元兴奋性和抑制性突触的发育和平衡方面发挥着不同的作用。
Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.
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