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Synaptic signalling in a network of dopamine neurons: what prevents proper intercellular crosstalk?
Author(s) -
Chen Yixi,
Kunath Tilo,
Simpson Joanna,
Homer Natalie,
Sylantyev Sergiy
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13910
Subject(s) - neuroscience , nmda receptor , crosstalk , inhibitory postsynaptic potential , dopamine , biology , receptor , neurotransmission , transplantation , midbrain , microbiology and biotechnology , central nervous system , medicine , biochemistry , physics , optics
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.