Expression and Functional Properties of NMDA and GABA_A Receptors during Differentiation of Human Induced Pluripotent Stem Cells into Ventral Mesencephalic Neurons

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S. A. Antonov^1,a*, E. V. Novosadova¹, A. G. Kobylyansky¹, S. N. Illarioshkin², V. Z. Tarantul¹, and I. A. Grivennikov¹

¹Institute of Molecular Genetics, Russian Academy of Sciences, 123182 Moscow, Russia

²Research Center of Neurology, 125367 Moscow, Russia

^* To whom correspondence should be addressed.

Received October 29, 2018; Revised November 29, 2018; Accepted November 29, 2018

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Ionotropic glutamate and GABA receptors regulate the differentiation and determine the functional properties of mature neurons. Both insufficient and excessive activity of these neurotransmission systems are associated with various nervous system diseases. Our knowledge regarding the expression profiles of these receptors and the mechanisms of their regulation during the differentiation of specialized human neuron subtypes is limited. Here the expression profiles of the NMDA and GABA_A receptor subunits were explored during in vitro differentiation of human induced pluripotent stem cells (iPSCs) into ventral mesencephalic neurons. The correlation between the neuronal maturation and the expression dynamics of these genes was investigated, and the functional activity of these receptors was assessed by calcium imaging. The role of NMDA and GABA_A receptors in neurite outgrowth and the development of spontaneous activity was analyzed using the viral transduction of neural progenitors with the reporter genes TagGFP and TagRFP. The data indicate that agonists of the investigated receptors can be employed for optimization of existing protocols for neural differentiation of iPSCs, in particular for acceleration of neuronal maturation.

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KEY WORDS: NMDA receptors, GABA_A receptors, induced pluripotent stem cells, mesencephalic neurons, differentiation

DOI: 10.1134/S0006297919030131

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