Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks

Yi Dong; Man Xiong; Yuejun Chen; Yezheng Tao; Xiang Li; Anita Bhattacharyya; Su-Chun Zhang

doi:10.1016/j.isci.2020.100829

Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks

iScience. 2020 Feb 21;23(2):100829. doi: 10.1016/j.isci.2020.100829. Epub 2020 Jan 9.

Authors

Yi Dong¹, Man Xiong², Yuejun Chen³, Yezheng Tao³, Xiang Li³, Anita Bhattacharyya³, Su-Chun Zhang⁴

Affiliations

¹ Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China; School of Physical Education & Health Care, East China Normal University, Shanghai 200241, China; Waisman Center, University of Wisconsin, Madison, WI 53705, USA. Electronic address: brainstein@fudan.edu.cn.
² Institute of Pediatrics, Children's Hospital, Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
³ Waisman Center, University of Wisconsin, Madison, WI 53705, USA.
⁴ Waisman Center, University of Wisconsin, Madison, WI 53705, USA; Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; Department of Neurology, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53705, USA; Program in Neuroscience & Behavioral Disorders, Duke-NUS Medical School, Singapore, Singapore. Electronic address: suchun.zhang@wisc.edu.

Abstract

Long-term potentiation and depression, inferred from analysis on brain slices, are considered the cellular processes underlying learning and memory formation. They have not so far been demonstrated in human stem cell-derived neurons. By expressing channelrhodopsin in hESCs-derived glutamate neurons and co-culturing them with GABA neurons, we found that blue light stimulation increased the frequency of miniature excitatory postsynaptic currents (mEPSCs) and decreased the ratio of paired pulse facilitation (PPF) in non-ChR2-expressing GABA neurons, indicating a facilitating action at the presynaptic terminals. When paired with postsynaptic depolarization, the repetitive stimulation significantly increased the amplitude of light-evoked EPSCs that persisted during the period, indicating long-term potentiation (LTP). In contrast, low-frequency light stimulation induced long-term depression (LTD). These effects were blocked by N-methyl-D-aspartic acid (NMDA) receptor antagonists, suggesting NMDA receptor-mediated synaptic plasticity in human neural networks. Furthermore, induced pluripotent stem cell (iPSC)-derived neurons of patient with Down syndrome showed absence of LTP or LTD. Thus, our platform offers a versatile model for assessing human neural plasticity under physiological and pathological conditions.

Keywords: Cellular Neuroscience; Neuroscience; Techniques in Neuroscience.

Abstract

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