Synaptic signalling in a network of dopamine neurons: What prevents proper inter-cellular crosstalk?

Yixi Chen, Tilo Kunath, Jo Simpson, Natalie Z M Homer, Sergiy Sylantyev

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Human embryonic stem cell (hESC) – derived midbrain dopamine (DA) neurons stand out as a cell source for transplantation with their sustainability and consistency superior to the formerly used fetal tissues. However, multiple studies of DA neurons in culture failed to register action potential (AP) generation in response to synaptic input. To test, whether this is due to deficiency of NMDA receptor (NMDAR) co-agonists Glycine and D-Serine released from astroglia in living tissue, we studied the functional properties of neural receptors in hESC-derived DA neuronal cultures. We find that, apart of insufficient amount of co-agonists, lack of interneuronal crosstalk is caused by hypofunction of synaptic NMDARs due to their direct inhibition by synaptically released dopamine. This inhibitory tone is independent from DA receptors and affects NMDARs via the modulation of co-agonist binding site.
Original languageEnglish
JournalFEBS Letters
Early online date16 Aug 2020
DOIs
Publication statusE-pub ahead of print - 16 Aug 2020

Keywords / Materials (for Non-textual outputs)

  • human embryonic stem cells
  • dopamine neurons
  • NMDA receptor
  • dopamine
  • synaptic signalling

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