Interleukin-10 Facilitates Glutamatergic Synaptic Transmission and Homeostatic Plasticity in Cultured Hippocampal Neurons

• Published in: International journal of molecular sciences Vol. 20; no. 13; p. 3375
• Main Authors: Nenov, Miroslav N, Konakov, Maxim V, Teplov, Ilia Y, Levin, Sergey G
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 09.07.2019; MDPI
• Subjects: Alanine - analogs & derivatives; Alanine - pharmacology; Animals; Calcium (intracellular); Calcium imaging; Calcium ions; Calcium signalling; Cell culture; Cells, Cultured; Cytokines; Electrophysiology; excitatory glutamatergic synaptic transmission; Excitatory postsynaptic potentials; Fluorescence; Fluorescence microscopy; Fura-2; Glutamatergic transmission; Hippocampal plasticity; Hippocampus; Hippocampus - cytology; Homeostatic plasticity; homeostatic synaptic plasticity; Inflammation; Interleukin 10; Interleukin-10 - pharmacology; mEPSC; Microscopy, Fluorescence; Neuronal Plasticity - drug effects; Neuronal-glial interactions; Neurons; Neurons - drug effects; Neurons - metabolism; Patch-Clamp Techniques; primary hippocampal culture; Probability distribution; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Synaptic plasticity; Synaptic transmission; Synaptic Transmission - drug effects; Tetrodotoxin - pharmacology; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; homeostatic synaptic plasticity; mEPSC; excitatory glutamatergic synaptic transmission; Interleukin-10; primary hippocampal culture
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20133375

Anti-inflammatory cytokines are known to exert neuroprotective action ameliorating aberrant neuronal network activity associated with inflammatory responses. Yet, it is still not fully understood if anti-inflammatory cytokines play a significant role in the regulation of synaptic activity under normal conditions. Thus, the aim of our study was to investigate the effect of Interleukin-10 (IL-10) on neuronal synaptic transmission and plasticity. For this we tested the effect of IL-10 on miniature excitatory postsynaptic currents (mEPSC) and intracellular Ca responses using whole-cell patch clamp and fluorescence microscopy in 13-15 DIV primary hippocampal neuroglial culture. We found that IL-10 significantly potentiated basal glutamatergic excitatory synaptic transmission within 15 min after application. Obtained results revealed a presynaptic nature of the effect, as IL-10 in a dose-dependent manner significantly increased the frequency but not the amplitude of mEPSC. Further, we tested the effect of IL-10 on mEPSC in a model of homeostatic synaptic plasticity (HSP) induced by treatment of primary hippocampal culture with 1 µM of tetrodotoxin (TTX) for a 24 h. It was found that 15 min application of IL-10 at established HSP resulted in enhanced mEPSC frequency, thus partially compensating for a decrease in the mEPSC frequency associated with TTX-induced HSP. Next, we studied if IL-10 can influence induction of HSP. We found that co-incubation of IL-10 with 1 µM of TTX for 24 h induced synaptic scaling, significantly increasing the amplitude of mEPSC and Ca responses to application of the AMPA agonist, 5-Fluorowillardiine, thus facilitating a compensatory postsynaptic mechanism at HSP condition. Our results indicate that IL-10 potentiates synaptic activity in a dose- and time-dependent manner exerting both presynaptic (short-term exposure) and postsynaptic (long-term exposure) action. Obtained results demonstrate involvement of IL-10 in the regulation of basal glutamatergic synaptic transmission and plasticity at normal conditions.