Loss of Long-Term Potentiation at Hippocampal Output Synapses in Experimental Temporal Lobe Epilepsy.

Patients suffering from temporal lobe epilepsy (TLE) show severe problems in hippocampus dependent memory consolidation. Memory consolidation strongly depends on an intact dialog between the hippocampus and neocortical structures. Deficits in hippocampal signal transmission are known to provoke disturbances in memory formation. In the present study, we investigate changes of synaptic plasticity at hippocampal output structures in an experimental animal model of TLE. In pilocarpine-treated rats, we found suppressed long-term potentiation (LTP) in hippocampal and parahippocampal regions such as the subiculum and the entorhinal cortex (EC). Subsequently we focused on the subiculum, serving as the major relay station between the hippocampus proper and downstream structures. In control animals, subicular pyramidal cells express different forms of LTP depending on their intrinsic firing pattern. In line with our extracellular recordings, we could show that LTP could only be induced in a minority of subicular pyramidal neurons. We demonstrate that a well-characterized cAMP-dependent signaling pathway involved in presynaptic forms of LTP is perturbed in pilocarpine-treated animals. Our findings suggest that in TLE, disturbances of synaptic plasticity may influence the information flow between the hippocampus and the neocortex.

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

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.