Abstracts

Rationale: Loss of consciousness occurs in complex partial limbic seizures. However, the mechanisms of unconsciousness are unclear. Our previous clinical research revealed an association between Ictal neocortical slow oscillations and loss of consciousness during complex focal seizures, and we have previously developed a rodent model with similar characteristics. The ictal neocortical slow waves are similar to those seen in sleep, indicating the potential mechanisms underlying unconsciousness. Therefore, a hypothesis can be raised that, as in slow wave sleep, decreased acetylcholine might be closely related to ictal slow waves in the neocortex and loss of consciousness. Methods: Temporal lobe seizures were induced by a 2-second, 60 Hz electrical stimulus in the dorsal hippocampus. Blood oxygen level dependent (BOLD) fMRI data were collected at 9.4 T in order to map neuronal increases and decreases. Individual neurons were recorded and labeled in the pedunculopontine tegmental nucleus using the juxtacellular method. We identified cholinergic cells using immunohistochemistry for choline acetyltransferase. Amperometry with choline-oxidase coated microelectrodes was used to record choline levels as a proxy for acetylcholine, and choline levels were recorded during seizures and toe pinch in the orbital frontal cortex and intralaminar thalamus. Results: Limbic seizures were > 30 seconds. BOLD fMRI decreased in cortex, thalamus, and brainstem tegmentum during complex partial seizures. Juxtacellular recordings from single labeled cholinergic neurons in brainstem also showed decreased firing during these seizures. Choline decreased in intralaminar thalamus and frontal cortex during complex partial seizures, while it increased in these two areas during generalized seizures and toe-pinch. Conclusions: These findings demonstrated, for the first time, decreased cholinergic neurotransmission in frontal cortex and thalamus during limbic seizures in rats. This suggests a possible mechanism to explain the slow oscillations and unconsciousness of complex partial seizures: (1) limbic seizures propagate from the hippocampus to limbic structures containing inhibitory projection neurons; (2) neuronal activity in arousal nuclei of the brainstem and basal forebrain decreases; and (3) this leads to decreased levels of arousal in the thalamus and cortex, and to impaired consciousness.