Chen Kai, Yang Guang, So Kwok-Fai, Zhang Li
Joint International Research Laboratory of CNS Regeneration, Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou 510632, China.
Department of Anesthesiology, Columbia University Medical Center, New York, NY, USA.
iScience. 2019 Jul 26;17:230-241. doi: 10.1016/j.isci.2019.06.040. Epub 2019 Jul 3.
Adult dendritic spines present structural and functional plasticity, which forms the basis of learning and memory. To provide in vivo evidence of spine plasticity under neurotoxicity, we generated an acute motor deficit model by single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into adult mice. Acute MPTP infusion impairs motor learnings across test paradigms. In vivo two-photon imaging further revealed MPTP-induced prominent dendritic spine loss and substantially increased calcium spikes in apical tufts of layer 5 pyramidal neurons in the motor cortex. MPTP infusion also decreased the activity of somatostatin (SST)-expressing inhibitory interneurons. Further chemogenetic re-activation of SST interneurons reversed MPTP-induced hyperactivation of dendrites, rescued spine loss, and enhanced motor learning. Taken together, our study reports MPTP-induced structural and functional deficits of dendritic spines and suggests the potency of modulating local inhibitory transmission to relieve neurological disorders.
成年树突棘具有结构和功能可塑性，这构成了学习和记忆的基础。为了提供神经毒性下树突棘可塑性的体内证据，我们通过向成年小鼠单次注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）建立了急性运动缺陷模型。急性MPTP注入会损害各种测试范式下的运动学习。体内双光子成像进一步揭示，MPTP会导致显著的树突棘丢失，并使运动皮层第5层锥体神经元顶端簇中的钙尖峰大幅增加。MPTP注入还降低了表达生长抑素（SST）的抑制性中间神经元的活性。进一步通过化学遗传学重新激活SST中间神经元可逆转MPTP诱导的树突过度激活，挽救树突棘丢失，并增强运动学习。综上所述，我们的研究报告了MPTP诱导的树突棘结构和功能缺陷，并表明调节局部抑制性传递对缓解神经疾病的有效性。
