Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus
Peripheral infections increase the propensity and severity of seizures in susceptible populations. We have previously shown that intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), elicits hypersusceptibility of mice to kainic acid (KA)-induced seizures. The present study was undertaken to determine whether this seizure hypersusceptibility entails alterations in glutamate signaling. Female C57BL/6 mice were i.p. injected with PIC, and after 24 hours, glutamate homeostasis in the hippocampus was monitored using the enzyme-based microelectrode arrays. PIC challenge robustly increased the level of resting extracellular glutamate. While presynaptic potassium-evoked glutamate release was not affected, glutamate uptake was profoundly impaired and non-vesicular glutamate release was augmented, indicating functional alterations of astrocytes. Electrophysiological examination of hippocampal slices from PIC-challenged mice revealed a several fold increase in the basal synaptic transmission as compared to control slices. PIC challenge also increased the probability of presynaptic glutamate release as seen from a reduction of paired-pulse facilitation (PPF) and synaptic plasticity as seen from an enhancement of long-term potentiation (LTP). Altogether, our results implicate a dysregulation of astrocytic glutamate metabolism and an alteration of excitatory synaptic transmission as the underlying mechanism for the development of hippocampal hyperexcitability, and consequently seizure hypersusceptibility following peripheral PIC challenge.
Digital Commons Citation
Hunsberger, H C.; Wang, D; Petrisko, T J.; and Alhowail, A, "Peripherally restricted viral challenge elevates extracellular glutamate and enhances synaptic transmission in the hippocampus" (2016). Clinical and Translational Science Institute. 427.