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

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Abstract

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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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (31571049 and 81561168022), the National Basic Research Program of China (2015CB910801), Zhejiang Provincial Natural Science Foundation of China (LR19H090001 and LD19H090002), a joint grant from the National Natural Science Foundation of China and the Research Grants Council of Hong Kong, China (8151101104 and N_HKUST625/15) and Fundamental Research Funds for the Central Universities of China. We appreciate the Core Facilities of Zhejiang University School of Medicine for technical support, and Mrs. SS Liu, ZXN Lin and GF Xiao for their help with confocal microscopy.

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Authors and Affiliations

  1. Department of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, 310058, China

    Qiang-Qiang Xia, Jing Xu, Tai-Lin Liao, Jie Yu, Jian-Hong Luo & Junyu Xu

  2. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou, 510632, China

    Lei Shi

  3. Division of Life Science, Division of Biomedical Engineering and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

    Jun Xia

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  1. Qiang-Qiang Xia
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Correspondence to Jian-Hong Luo or Junyu Xu.

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Xia, QQ., Xu, J., Liao, TL. et al. Neuroligins Differentially Mediate Subtype-Specific Synapse Formation in Pyramidal Neurons and Interneurons. Neurosci. Bull. 35, 497–506 (2019). https://doi.org/10.1007/s12264-019-00347-y

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  • DOI: https://doi.org/10.1007/s12264-019-00347-y

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