ADAPTIVE REMODELING OF SUBICULAR PYRAMIDAL NEURONS IN MESIAL TEMPORAL LOBE EPILEPSY

Mesial temporal lobe epilepsy (MTLE) is often accompanied by hippocampal sclerosis including cell death in CA1 and CA3. The subiculum as the main hippocampal output region represents with its specific connectivity an important relay station of the epileptic network. Previously we showed a strong loss of subicular interneurons. It remained, however, unclear, whether and how the excitatory neuron population is altered. Among principal cells of the subiculum, the subgroup expressing Purkinje-cell protein 4 (PCP4) is of particular interest as these neurons exhibit more stable firing rates and a reduced propensity for hyperexcitability.
To investigate MTLE we used the intrahippocampal kainate (KA) mouse model. We analyzed neuronal density in the subiculum in the chronic stage of MTLE and performed immunohistochemistry to investigate PCP4 expression. Furthermore, we used whole-cell patch clamp to evaluate the electrophysiological conditions of pyramidal neurons not only in the subiculum of KA mice, but also in human slices from MTLE surgery.
We found a prominent reduction of neuronal density in the ventral subiculum of KA mice. In contrast, PCP4 was not only expressed in deep layers, but also de novo in superficial layers of the ventral subiculum. Preliminary results in human tissue suggest a similar pattern. Whole-cell patch clamp recordings in current-clamp indicated that pyramidal neurons exhibit action potentials with a reduced peak amplitude and slower rise times. In human slices we observed a lower resting membrane potential of pyramidal neurons compared to mice. In summary, our results reveal that the subiculum undergoes compensatory changes under epileptic conditions.