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

Yixi Chen, Tilo Kunath, Joanna Simpson, Natalie Homer, Sergiy Sylantyev* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 upon synaptic input. To test whether this is due to deficiency of NMDA receptor (NMDAR) coagonists released from astroglia, we studied the functional properties of neural receptors in hESC-derived DA neuronal cultures. We find that, apart from an insufficient amount of coagonists, lack of interneuronal crosstalk is caused by hypofunction of synaptic NMDARs due to their direct inhibition by synaptically released DA. This inhibitory tone is independent of DA receptors and affects the NMDAR coagonist binding site.

Original languageEnglish
Pages (from-to)3272-3292
Number of pages21
JournalFEBS LETTERS
Volume594
Issue number20
Early online date30 Aug 2020
DOIs
Publication statusPublished - Oct 2020

Keywords

  • human embryonic stem cells
  • dopamine neurons
  • NMDA receptor
  • dopamine
  • synaptic signalling
  • TISSUE-PLASMINOGEN ACTIVATOR
  • ADULT NEUROGENESIS
  • SUBUNIT COMPOSITION
  • NEURAL PRECURSORS
  • D-SERINE
  • EMBRYONIC STEM-CELLS
  • NMDA-RECEPTORS
  • RECEPTOR-MEDIATED INHIBITION
  • IN-VITRO DIFFERENTIATION
  • PARKINSONS-DISEASE

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