Parallel pathways to decreased subcortical arousal in focal limbic seizures

Focal limbic seizures can cause loss of consciousness. Previous work suggests that hippocampal seizures can increase activity in the lateral septum (LS) and decrease cholinergic output from the basal forebrain (BF), leading to deficits in conscious arousal. The mechanism by which LS and BF interact is unclear. In this study, we used anterograde and retrograde tracing to investigate anatomical pathways connecting LS and BF. We found that LS projects directly to BF and indirectly to BF via the thalamic paratenial nucleus (PT). Acute electrophysiology experiments during electrically induced focal limbic seizures showed that multiunit activity decreased in PT during the ictal period and was associated with increased cortical slow wave activity. These results suggest that LS could functionally inhibit BF during a seizure directly, or could indirectly decrease excitatory output to BF through PT. Further work investigating such parallel inhibitory and excitatory pathways to subcortical arousal may ultimately lead to new treatment targets for consciousness-impairing limbic seizures.