AUTHOR=Shypshyna Mariia , Kolesnyk Oksana , Fedulova Svitlana , Veselovsky Nickolai TITLE=Insulin modulates the paired-pulse plasticity at glutamatergic synapses of hippocampal neurons under hypoinsulinemia JOURNAL=Frontiers in Cellular Neuroscience VOLUME=17 YEAR=2023 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1132325 DOI=10.3389/fncel.2023.1132325 ISSN=1662-5102 ABSTRACT=

Hypoinsulinemia is a pathological consequence of diabetes mellitus that can cause a number of complications of the central and peripheral nervous system. Dysfunction of signaling cascades of insulin receptors under insulin deficiency can contribute to the development of cognitive disorders associated with impaired synaptic plasticity properties. Earlier we have shown that hypoinsulinemia causes a shift of short-term plasticity in glutamatergic hippocampal synapses from facilitation to depression and apparently involves mechanisms of glutamate release probability reduction. Here we used the whole cell patch-clamp recording of evoked glutamatergic excitatory postsynaptic currents (eEPSCs) and the method of local extracellular electrical stimulation of a single presynaptic axon to investigate the effect of insulin (100 nM) on the paired-pulse plasticity at glutamatergic synapses of cultured hippocampal neurons under hypoinsulinemia. Our data indicate that under normoinsulinemia additional insulin enhances the paired-pulse facilitation (PPF) of eEPSCs in hippocampal neurons by stimulating the glutamate release in their synapses. Under hypoinsulinemia, insulin did not have a significant effect on the parameters of paired-pulse plasticity on neurons of PPF subgroup, which may indicate the development of insulin resistance, while the effect of insulin on PPD neurons indicates its ability to recover the form normoinsulinemia, including the increasing probability of plasticity to the control level in of glutamate release in their synapses.