Structural and molecular differentiation of cultured human neurons is accompanied by alterations of spontaneous and evoked calcium dynamics

Journal article

Negi, Deepika, Shorter, Susan, Goodhall, Iain, Razansky, Daniel, Shergil, Sukhi and Ovsepian, Saak V 2025. Structural and molecular differentiation of cultured human neurons is accompanied by alterations of spontaneous and evoked calcium dynamics. Scientific Reports. 15 (1), p. 34196. https://doi.org/10.1038/s41598-025-15561-0
AuthorsNegi, Deepika, Shorter, Susan, Goodhall, Iain, Razansky, Daniel, Shergil, Sukhi and Ovsepian, Saak V
AbstractDuring development, neuronal precursors transform from a pluripotent state into specialized neurons. While much research has been conducted into morphological and molecular changes, there is a pressing need to define accompanying functional alterations. We used immunofluorescence microscopy and live imaging in SH-SY5Y-derived human neurons to elucidate the relationship between structural and molecular differentiation with evoked and spontaneous Ca2+ dynamics. In the undifferentiated state expressing trace amounts of neuronal markers, SH-SY5Y cells maintain spontaneous high-amplitude slow Ca2+ oscillations, with their stimulation by carbochol activating low-amplitude Ca2+ transients. Driving SH-SY5Y cells into the 2CL state by retinoic acid facilitated the outgrowth of neurites and expression of neuron-specific proteins. These changes are accompanied by the abolition of Ca2+ oscillations. Differentiating SH-SY5Y cells into definitive neurons by a cocktail of retinoic acid and BDNF induced their polarization and enrichment with specific neuronal markers, accompanied by a resurgence of spontaneous Ca2+ oscillations but with faster kinetics. The carbachol-induced rise of Ca2+ in these cells showed a higher peak and biphasic decay. At all developmental stages, Ca2+ transients in response to ionomycin were indistinguishable. These findings lead us to conclude that a switch of Ca2+ dynamics accompanies structural and molecular differentiation of SH-SY5Y cell-derived human neurons, contributing to the developmental process.
KeywordsSpontaneous activity; SH-SY5Y cells; Calcium imaging; Molecular polarization; Neuroblastoma-derived neurons; Calcium; Tretinoin; Brain-Derived Neurotrophic Factor; Cell differentiation; Calcium signalling
Year2025
JournalScientific Reports
Journal citation15 (1), p. 34196
PublisherSpringer Nature
ISSN2045-2322
Digital Object Identifier (DOI)https://doi.org/10.1038/s41598-025-15561-0
Official URLhttps://www.nature.com/articles/s41598-025-15561-0
FunderSwiss National Science Foundation
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Online01 Oct 2025
Print01 Oct 2025
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Accepted08 Aug 2025
Deposited02 Oct 2025
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Biased interpretation in paranoia and its modification
George Savulich, Annabel Edwards, Sara Assadi, Husniye Guven, Emily Leathers-Smith, Sukhi Shergill and Jenny Yiend 2020. Biased interpretation in paranoia and its modification. Journal of Behavior Therapy and Experimental Psychiatry. 69, p. 101575. https://doi.org/10.1016/j.jbtep.2020.101575
Acute oxytocin effects in inferring others' beliefs and social emotions in people at clinical high risk for psychosis
André Schmidt, Cathy Davies, Yannis Paloyelis, Nicholas Meyer, Andrea De Micheli, Valentina Ramella-Cravaro, Umberto Provenzani, Yuta Aoki, Grazia Rutigliano, Marco Cappucciati, Dominic Oliver, Silvia Murguia, Fernando Zelaya, Paul Allen, Sukhi Shergill, Paul Morrison, Steve Williams, David Taylor, Stefan Borgwardt, Hidenori Yamasue, Philip McGuire and Paolo Fusar-Poli 2020. Acute oxytocin effects in inferring others' beliefs and social emotions in people at clinical high risk for psychosis. Translational Psychiatry. 10 (203). https://doi.org/10.1038/s41398-020-00885-4
Real-world effectiveness of admissions to a tertiary treatment-resistant psychosis service: 2-year mirror-image study
Cecilia Casetta, Fiona Gaughran, Ebenezer Oloyede, Juliana Onwumere, Megan Pritchard, Sukhi S. Shergill, Eromona Whiskey and James Hunter MacCabe 2020. Real-world effectiveness of admissions to a tertiary treatment-resistant psychosis service: 2-year mirror-image study. BJPsych Open. 6 (5), p. E82. https://doi.org/10.1192/bjo.2020.51
Dopamine manipulations drive changes in information sampling in healthy volunteers
Shergill, S. 2019. Dopamine manipulations drive changes in information sampling in healthy volunteers. Journal of Psychopharmacology. 33 (6), pp. 670-677. https://doi.org/10.1177/0269881118822080
Integrated care in mental health: Next steps after the NHS Long Term Plan
Derek K. Tracy, Kara Hanson, Tom Brown, Adrian J. B. James, Holly Paulsen, Zoé Mulliez and Sukhwinder Shergill 2019. Integrated care in mental health: Next steps after the NHS Long Term Plan. British Journal of Psychiatry. 214 (6), pp. 315-317. https://doi.org/10.1192/bjp.2019.46
Cognitive correlates of abnormal myelination in psychosis
Lucy D. Vanes, Elias Mouchlianitis, Erica Barry, Krisna Patel, Katie Wong and Sukhwinder S. Shergill. 2019. Cognitive correlates of abnormal myelination in psychosis. Scientific Reports. 9 (5162). https://doi.org/10.1038/s41598-019-41679-z
Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists
Rishi K. Patel, Alice M. Moore, Susan Piper, Mark Sweeney, Eromona Whiskey, Graham Cole, Suhki Shergill and Carla M. Plymen 2019. Clozapine and cardiotoxicity – A guide for psychiatrists written by cardiologists. Psychiatry Research. 282, p. 112491. https://doi.org/10.1016/j.psychres.2019.112491
Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia
Mark Sweeney, Eromona Whiskey, Rishi K. Patel, Derek K. Tracy, Sukhi S. Shergill and Carla M. Plymen 2019. Understanding and managing cardiac side-effects of second-generation antipsychotics in the treatment of schizophrenia. BJPsych Advances. 26 (1), pp. 26-40. https://doi.org/10.1192/bja.2019.49
Real-world outcomes in the management of refractory psychosis
Amir Krivoy, Dan Joyce, Derek Tracy, Fiona Gaughran, James MacCabe, John Lally, Eromona Whiskey, S. Neil Sarkar and Sukhwinder S. Shergill 2019. Real-world outcomes in the management of refractory psychosis. Journal of Clinical Psychiatry. 80 (5), p. 18m12716. https://doi.org/10.4088/JCP.18m12716
Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia
Lucy D. Vanes, Elias Mouchlianitis, Krisna Patel, Erica Barry, Katie Wong, Megan Thomas, Timea Szentgyorgyi, Dan Joyce and Sukhwinder Shergill 2019. Neural correlates of positive and negative symptoms through the illness course: an fMRI study in early psychosis and chronic schizophrenia. Scientific Reports. 9, p. 14444. https://doi.org/10.1038/s41598-019-51023-0
Girls-boys: an investigation of gender differences in the behavioral and neural mechanisms of trust and reciprocity in adolescence
Imke L. J. Lemmers-Jansen, Anne-Kathrin J. Fett, Sukhi Shergill, Marlieke T. R. van Kesteren and Lydia Krabbendam 2017. Girls-boys: an investigation of gender differences in the behavioral and neural mechanisms of trust and reciprocity in adolescence. Frontiers in Human Neuroscience. 13 (257).