Abstracts

Rationale: The hippocampus is one of the key structures involved in the generation of spontaneous epileptic seizures in Medial Temporal Lobe Epilepsy (MTLE). Seizures originating in the medial temporal lobe are frequently associated with impaired consciousness, which is thought to be partly caused by the widespread inhibition of neuronal activity in the fronto-parietal association cortex. In this study, neuronal ensemble and LFP recordings were simultaneously conducted in the hippocampus and parietal association cortex in a MTLE rat model with spontaneous seizures in order to better understand 1) neuronal firing dynamics associated with the generation of spontaneous epileptic seizures in MTLE and 2) the effect of seizures, generated in medial temporal lobe, on activity of neurons in parietal association cortex. Methods: Eight weeks after induction of limbic status epilepticus by bilateral perforant path stimulation (n=3) or intrahippocampal kainic acid injection (n=1), four rats that consistently exhibited multiple seizures per day were selected for implantation of an 18-tetrode microdrive above the right parietal association cortex and hippocampus (AP: -3.8 mm; ML: - 2mm relative to bregma). 24-hour recordings were carried out with some of the tetrodes positioned in the parietal association cortex and others in the hippocampal cell layers. Spiking activity was analyzed offline using standard spike sorting software and methods. Epileptic seizures were detected based on local field potentials. Results: Analysis of neuronal firing rates in relation to epileptic seizures shows that the majority of neurons in not only the hippocampus but also the parietal association cortex shut down within the first second of seizure onset. Within the first 10-30 seconds after seizure onset neurons in parietal association cortex and hippocampus show large variability in firing patterns, and those patterns are preserved across seizures and neurons. On average, 1-3 minutes before seizure onset, firing rates of a subset of neurons begin to change progressively. For the majority of neurons firing rates increase, although in some cases firing rates decrease. This increase in firing rates seems to coincide with a general tendency of the brain to enter an activated state (REM, awake-like) about 1-5 minutes prior to the majority of the seizures. Conclusions: In line with previous studies in rats and in patients that recorded action potentials in ictal onset regions, this study shows a large variability in neuronal firing patterns rather than hypersynchronous firing at the onset of epileptic seizures. The majority of neurons in parietal association cortex were inhibited at the very onset of limbic seizures. This suggests that spontaneous limbic seizures very rapidly influence neural activity in regions that are considered to be important substrates for consciousness. This project is funded by AIHS Polaris award to B.M., by NERF, by the Flemisch Fund for Scientific research.