Glial cells inhibition affects the incidence of metaplasticity in the hippocampus of Pentylentetrazole-induced kindled rats

Epilepsy is characterized by the unpredictability but recurrence of seizures caused by the synchronized aberrant firing of neuronal populations. It has been shown that astrocytes (one of the most prominent glial cells) are ideally positioned to induce or contribute to neural network synchronization. Although astrocytes cannot generate action potentials, they have the capacity to sense and respond to neuronal activity, which allows them to function as homeostatic regulators of synaptic interactions. Considering the necessity of astrocyte-neuron bidirectional interactions in synaptic transmission and plasticity, in the current study, the role of astrocytes in synaptic metaplasticity and resultant behavioral seizures induced by Pentylentetrazole (PTZ) was assessed. Rats were kindled by intraperitoneal (i.p.) injection of PTZ (30 mg/kg/48 h). A glial cell inhibitor, Fluorocitrate (FC), was injected into the right lateral cerebral ventricle of the rat 30 min before PTZ during kindling progress. The maximal seizure stage (SS), stage 2 and 4 latency (S2L, S4L), stage 4 and 5 duration (S4D, S5D), and seizure duration (SD) were all assessed 20 min after PTZ administration by observation. Following Schaffer collateral stimulation, in vivo field, potential recordings from the CA1 area of the hip-pocampus were employed to assess the metaplasticity induced in kindled rats. The inhibition of glial cells during the kindling process significantly lowered SS, S4D&S5D and increased S4L (Two-way ANOVA, Bonferroni Posttest, P < 0.05, P < 0.01, and P < 0.001). In comparison to the control group, electrophysiological data demonstrated that HFS-induced LTP in kindled animals was decreased (Unpaired t-test, P < 0.05). Glial cell inhibition prevented PTZ's effect on LTP. Our data imply that kindling altered CA1 pyramidal neurons' vulnerability to synaptic plasticity. This shift in neuronal plasticity (metaplasticity) is mediated in part by glial cells and is important in the for-mation of seizure symptoms. As a result, glial cell inhibition was found to alleviate seizure behavior. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

In this study, the role of astrocytes in seizures induced by PTZ was assessed, and it was found that inhibiting astrocytes can alleviate seizure behavior. Inhibition of astrocytes reduced the severity and duration of seizures and decreased the changes in synaptic plasticity.