Episodic-like memory and oscillatory patterns in the hippocampus and medial prefrontal cortex of adult rats subjected to early-life seizures

Abstract

Several clinical and experimental studies have provided convincing evidence showing that early-life seizure (ELS) events trigger late spontaneous seizures and/or cognitive deficits; however, the underlying mechanism of such late changes remains unclear. Neuronal cell loss and mossy fibre sprouting may be absent in the presence of later seizures and cognitive deficits. On the other hand, inflammatory process associated to microglia over-activation, besides plasticity-related events at a molecular/cellular level, usually occurs not only in the hippocampus but probably also in extra-limbic circuits. One possibility to probe neuronal plasticity on the network level in vivo is quantifying oscillatory activity patterns of local field potentials (LFPs). Therefore, further studies are required using freely moving electrophysiological recordings throughout an animal's life and attendant memory tasks in order to dissociate different phases and facets of the episodic-like memory processing. In this sense, the event arena paradigm represents an opportunity to investigate the effect of ELS into adulthood, specifically with respect to (1) the temporal dynamics of systems memory consolidation, and (2) the hippocampus/medial prefrontal cortex (mPFC) encoding responsible for enabling relevant new paired associates (PA; flavour/place) to be assimilated into an original schema. Therefore, the aim of the present project is, in adult animals previously subjected to ELS, to investigate the relationship between oscillatory activity in hippocampus and mPFC with the cognitive performance of an episodic-like memory task. In particular, we aim to verify whether the inhibition of ELS-associated inflammation process by minocycline treatment attenuates the later oscillatory effects, likewise later learning ability impairments in the event-arena. Rats will be subjected to ELS induction by Li-PILO at P12 and seven additional daily injections of minocycline. Control groups will be treated only with its drugs vehicles. Forty-eight days after ELS, electrodes in the mPFC and in CA1 of the hippocampus will be stereotaxically implanted under anaesthesia. Rats will be subjected to the event arena task, LFPs will be recorded daily using a telemetry system and eventual cellular loss and changes in microglia will be examined. (AU)