The present work aimed to test whether the induction of cortical long-term potentiation (LTP) was able to prevent the presynaptic plasticity impairment in the hippocampus (CA1)-medial prefrontal cortex (mPFC) pathway induced by hippocampal after-discharge (AD; epileptic activity) or systemic injection of ketamine (KET; pharmacological model of psychosis). Electrodes were stereotaxically positioned into CA1 and mPFC in urethane-anesthetized rats. Monophasic paired-pulses of electrical stimuli were applied to CA1 in order to evoke field post-synaptic potentials (P1 and P2) in the mPFC every 20s. Short-term plasticity was evaluated by measuring paired-pulse facilitation (PPF), defined as the amplitude ratio P2/P1. After 90min of baseline recordings, three independent groups of animals received hippocampal-AD, KET-S(+) (12.5mg/kg, i.p.) or vehicle (NaCl 0.15M) followed by 120min of evoked response monitoring. In an additional experiment, two applications of high-frequency stimuli (HFS) were given at 30 and 60min after baseline. Thirty minutes after the second HFS, the rats received KET, AD or vehicle and their cortical evoked potentials were monitored for further 120min. Our results showed that AD significantly decreased (-50%) whereas KET enhanced (+10%) CA1-mPFC basal synaptic transmission. In addition, AD and KET similarly impaired short-term plasticity in the mPFC (-15%). Interestingly, pre-induction of LTP in the mPFC prevented the PPF disruption induced by KET and AD. Altogether, our findings support recent evidences that positive allosteric modulators of NMDA and AMPA receptors attenuate cognitive impairments in animal models of psychosis. We believe that controlled HFS in CA1 can be a useful tool to better understand how to prevent synaptic plasticity disruptions observed in experimental models of psychosis and pos-ictal psychosis.
post-ictal psychosis; synaptic plasticity; CA1-medial prefrontal cortex pathway; long-term potentiation; afterdischarge; ketamine
