Decreased locus coeruleus multiunit activity in a mouse model of temporal lobe seizures with impaired consciousness

Exp Neurol. 2025 Apr 4:115233. doi: 10.1016/j.expneurol.2025.115233. Online ahead of print.

ABSTRACT

People with temporal lobe epilepsy often suffer debilitating loss of consciousness during seizures. Rodent models have previously implicated the inhibition of brainstem and basal forebrain cholinergic neurons in the cortical impairment during these periods of impaired consciousness. However, there are still other subcortical pathways that remain largely unexplored. Our goal was to record multiunit activity in the locus coeruleus (LC) in an awake mouse model to help elucidate its potential role in this pathophysiology. Recordings were performed using head-fixed mice running on a wheel with chronically implanted bipolar electrodes in the right orbitofrontal cortex and bilateral dorsal hippocampi. Focal limbic seizures were induced via the application of current pulses into the HC and multiunit recordings were simultaneously obtained from the LC. We observed a significant decrease in firing of LC neurons during ictal impairment of running wheel behavior. There was also a concurrent, significant increase in power in the 1-4 Hz band in the OFC. This provides evidence of a LC noradrenergic pathway contributing to depressed arousal in focal limbic seizures. Further elucidation of these, and other pathways, will contribute better mechanistic understanding of ictal unconsciousness and may lead to novel, improved treatments for people with epilepsy.

PMID:40189126 | DOI:10.1016/j.expneurol.2025.115233