Plasticity of Synaptic Transmission in Human Stem Cell-Derived Neural Networks
Open accessAbstract
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.
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Neurons generated from iPSCs derived from individuals with DS have little to no capacity for either LTP or LTD in vitro.
“Moreover, neurons generated from iPSCs derived from individuals with DS have little to no capacity for either LTP or LTD in vitro132, and when transplanted into the mouse brain, these neurons have reduced structural plasticity relative to controls133.”
From Consequences of trisomy 21 for brain development in Down syndrome (2024) · cites this paper as [132]
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- Authors
- Dong, Y., Xiong, M., Chen, Y., Tao, Y., Li, X., Bhattacharyya, A., & Zhang, S.-C.
- Affiliations
- University of Wisconsin–Madison (US)
- Fudan University (CN)
- Corresponding author
- Dong, Yi
- Zhang, Su-Chun
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 23
- Issue
- 2
- Pages
- 100829
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC6993006
- OpenAlex
- W3000101741
- Cited by
- 19
- References
- 42
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 7 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 1
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute of Child Health and Human Development
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- synaptic plasticity, long-term potentiation, long-term depression, human induced pluripotent stem cell-derived neurons, human embryonic stem cell-derived neurons, channelrhodopsin, paired-pulse facilitation, miniature excitatory postsynaptic currents, NMDA receptor, Down syndrome, artificial neural networks, learning and memory
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