Abstracts

Rationale: Rat models have previously been studied to identify potential drivers of impaired consciousness during temporal lobe epilepsy. Using these, inhibition of brainstem and basal forebrain cholinergic neurons has been identified as one of these drivers. However, there are still many unknowns surrounding the subcortical pathway affecting seizure-related depression in cortical function. Recording multi-unit activity in the locus coeruleus (LC) in an awake mouse model of temporal lobe seizures will help describe the role of a separate neurotransmitter pathway by investigating subcortical noradrenergic modulation during ictal unconsciousness.

Methods: Mice were head-fixed on a running wheel. Local field potentials were measured with chronically implanted bipolar electrodes in the right orbitofrontal cortex and bilateral hippocampi. Induction of focal limbic seizures was accomplished by the application of current pulses (2 s, 60 Hz) into the hippocampus. Neurons in the locus coeruleus were recorded using a high-impedance, tungsten microelectrode (2-4 MΩ resistance; FHC). Electrode placements were confirmed histologically. The electrode location was verified using DiI, and the LC was visualized using anti-tyrosine hydroxylase fluorescent staining.

Results: Induction of focal limbic seizures in the mouse model led to slow wave activity in the orbital frontal cortex resembling human temporal lobe seizures, accompanied by behavioral arrest. Recordings from the locus coeruleus demonstrated a statistically significant (p< 0.05) decrease in multiunit activity (quantified as Vrms) during focal limbic seizures with a simultaneous significant increase in 1-4 Hz power in the lateral orbitofrontal cortex (n=8). Noradrenergic neurons in the locus coeruleus and electrode traces were successfully identified by histology.