Department of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou, 510632, China.
Neurosci Bull. 2019 Jun;35(3):497-506. doi: 10.1007/s12264-019-00347-y. Epub 2019 Feb 21.
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.
神经黏附素（NLs）是突触后细胞黏附蛋白，在突触形成和兴奋-抑制平衡中发挥重要作用。在人类遗传和动物模型研究中，NLs 与自闭症有关，并影响几个脑区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上，而 NLs 在中间神经元中的功能仍有待了解。为了探索 NLs 在锥体神经元和中间神经元的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中通过病毒介导的 shRNA 敲低 NLs，并检查两种主要类型神经元中的突触。我们的结果表明，在这两种类型的神经元中，NL1 和 NL3 参与兴奋性突触形成，而 NL2 参与 GABA 能突触形成。有趣的是，NL1 比 NL3 更特异性地影响 GABA 能突触形成，而 NL2 更优先地影响锥体神经元中的兴奋性突触密度。总之，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中兴奋性和抑制性突触的发育和平衡中发挥不同的作用。
