Slow and fast cortical cholinergic arousal is reduced in a mouse model of focal seizures with impaired consciousness

Patients with focal temporal lobe seizures often experience loss of
consciousness associated with cortical slow waves, like those in deep
sleep. Previous work in rat models suggests that decreased subcortical
arousal causes depressed cortical function during focal seizures. However,
these studies were performed under light anesthesia, making it impossible
to correlate conscious behavior with physiology. We show in an awake mouse
model that electrically induced focal seizures in the hippocampus cause
impaired behavioral responses to auditory stimuli, cortical slow waves,
and reduced mean cortical high-frequency activity. Behavioral responses
are related to cortical cholinergic release at two different timescales.
Slow state-related decreases in acetylcholine correlate with overall
impaired behavior during seizures. Fast phasic acetylcholine release is
related to variable spared or impaired behavioral responses with each
auditory stimulus. These findings establish a strong relationship between
decreased cortical arousal and impaired consciousness in focal seizures
which may help guide future treatment.