Enhancement of long-term potentiation at CA1-subiculum synapses in MK-801-treated rats.

The subiculum relays information from the hippocampus to brain regions involved in schizophrenia. Using the MK-801 model of psychosis in rats, the study examined changes in synaptic transmission and plasticity at CA1-subiculum synapses 4 hours, 24 hours, and 4 weeks after treatment. Systemic MK-801 facilitated long-term potentiation (LTP) at 24 hours compared to controls, but LTP returned to normal levels after 4 weeks. This delayed facilitation suggests a novel form of metaplasticity, offering insight into how NMDA receptor antagonists affect synaptic efficacy over time.

Study at a glance

Abstract

The subiculum plays a key role in processing neuronal information from the hippocampus to different cortical and subcortical brain regions. The subicular projections to the nucleus accumbens and the prefrontal cortex have received increasing attention, as alterations of their activity seem to be involved in schizophrenia. Phencyclidine and other non-competitive antagonists of NMDA receptors (such as ketamine and MK-801) induce psychotic effects in humans that closely resemble the positive, negative and cognitive symptoms of schizophrenia. Using the MK-801 model of psychosis, we investigated the time course of alterations of synaptic transmission and plasticity at CA1-subiculum synapses of hippocampal brain slices 4 h, 24 h and 4 weeks after MK-801 treatment. We report here that systemic application of MK-801 causes a facilitation of LTP at CA1-subiculum synapses 24 h after treatment as compared with control LTP. Four weeks after MK-801 treatment, the magnitude of LTP reversed to control values. The priming of LTP 24 h after systemic application of MK-801 suggest a new form of metaplasticity that sheds light on the delayed facilitating effect of this drug on synaptic efficacy.