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

Yixi  Chen; Tilo Kunath; Joanna  Simpson; Natalie  Homer; Sergiy Sylantyev

doi:10.1002/1873-3468.13910

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

The Rowett Institute of Nutrition and Health

Research output: Contribution to journal › Article › peer-review

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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 language	English
Pages (from-to)	3272-3292
Number of pages	21
Journal	FEBS LETTERS
Volume	594
Issue number	20
Early online date	30 Aug 2020
DOIs	https://doi.org/10.1002/1873-3468.13910
Publication status	Published - Oct 2020

Bibliographical note

Open access via the Jisc Wiley Agreement
Acknowledgements:
This work was supported by the Chancellor’s Fellow Grant and the Moray Endowment Grant to SS. YC and TK were supported by Medical Research Council (Award Number: MR/K017276/1) and UK Centre for Mammalian Synthetic Biology. The authors gratefully acknowledge the financial support of NHS Research Scotland (NRS), through Edinburgh Clinical Research Facility. Authors thank Prof. Andrey Abramov (UCL) for his valuable suggestions on design of this study and Scott Denham from the Mass Spectrometry Core for his technical expertise and assistance in this work.

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/1873-3468.13910Licence: CC BY

Chen_etal_FEBSL_Synaptic_signaling_VOR
© 2020 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
Final published version, 4.09 MBLicence: CC BY

Cite this

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

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.",

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

Abstract

Bibliographical note

Keywords

UN SDGs

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