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Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function

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Abstract

Rho-associated kinases (ROCKs) are serine-threonine protein kinases that act downstream of small Rho GTPases to regulate the dynamics of the actin cytoskeleton. Two ROCK isoforms (ROCK1 and ROCK2) are expressed in the mammalian central nervous system. Although ROCK activity has been implicated in synapse formation, whether the distinct ROCK isoforms have different roles in synapse formation and function in vivo is not clear. Here, we used a genetic approach to address this long-standing question. Both Rock1+/− and Rock2+/− mice had impaired glutamatergic transmission, reduced spine density, and fewer excitatory synapses in hippocampal CA1 pyramidal neurons. In addition, both Rock1+/− and Rock2+/− mice showed deficits in long-term potentiation at hippocampal CA1 synapses and were impaired in spatial learning and memory based on the water maze and contextual fear conditioning tests. However, the spine morphology of CA1 pyramidal neurons was altered only in Rock2+/− but not Rock1+/− mice. In this study we compared the roles of ROCK1 and ROCK2 in synapse formation and function in vivo for the first time. Our results provide a better understanding of the functions of distinct ROCK isoforms in synapse formation and function.

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Acknowledgements

We thank Dr. R William Caldwell (Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA, 30912-2300, USA) for providing the transgenic Rock1+/− and Rock2+/− mice. This work was supported by the National Science Foundation of China (81774406 and 31571041), the Guangdong Innovative and Entrepreneurial Research Team Program (Natural Science) (2017KCXTD006), Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (2016), and the Scientific Research and Innovation Team Program of Guangzhou University of Chinese Medicine (2017KYTD03).

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  1. Jinglan Yan, Youcan Pan and Xiaoyan Zheng have contributed equally to this work.

Authors and Affiliations

  1. South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Jinglan Yan, Youcan Pan, Xiaoyan Zheng, Chuanan Zhu, Yu Zhang, Guoqi Shi, Yongjun Chen & Nenggui Xu

  2. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China

    Lin Yao

  3. Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, 510006, China

    Youcan Pan

  4. Guangdong Province Key Laboratory of Psychiatric Disorders, Southern Medical University, Guangzhou, 510515, China

    Yongjun Chen

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  1. Jinglan Yan
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Yan, J., Pan, Y., Zheng, X. et al. Comparative Study of ROCK1 and ROCK2 in Hippocampal Spine Formation and Synaptic Function. Neurosci. Bull. 35, 649–660 (2019). https://doi.org/10.1007/s12264-019-00351-2

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