Midbrain Reticular Formation as a Subcortical Substrate for Impaired Consciousness in Focal Limbic Seizures
Abstract number :
3.075
Submission category :
1. Basic Mechanisms / 1E. Models
Year :
2024
Submission ID :
123
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: Yang Zheng, MD, PhD – Departments of Neurology, Yale University School of Medicine
Jiayang Liu, PhD – Yale University School of Medicine
Samiksha Copra, MD, PhD – Departments of Neurology, Yale University School of Medicine
Sarah McGill, PhD – Departments of Neurology, Yale University School of Medicine
Lim-anna Sieu, PhD – Yale University School of Medicine
Stefan sumsky, PhD – Departments of Neurology, Yale University School of Medicine
Hal Blumenfeld, MD, PhD – Yale University School of Medicine
Rationale: Impaired consciousness is one major reasons for morbidity and mortality of seizures. Maintenance of consciousness, on the other hand, requires coordination of brainstem and forebrain activity. Previous work suggested reduced blood-oxygen-level-dependent signals in the midbrain, a region crucial for normal arousal, during focal limbic (hippocampal) seizures. However, how the midbrain participates in ictal impairment of consciousness remains unknown.
Methods: We used an awake-behaving mouse model, where focal limbic seizures were induced by hippocampal stimulation. Local field potentials were recorded from the hippocampus and the orbitofrontal cortex. Licking responses to auditory stimuli and speed of wheel running were used to test consciousness during seizures. Simultaneously, we conducted multiunit recordings from the reticular formation in the midbrain. Correlation between midbrain neuronal firing and behavioral tests was analyzed.
Results: The awake mouse model showed focal hippocampal seizures either with or without impaired consciousness, similar to the findings in patients with temporal lobe epilepsy. Ictal impairment in consciousness was accompanied by slow waves and significantly increased delta power in the orbitofrontal cortex, reduced wheel speed, and decreased licking responses to auditory stimuli (n = 15). During focal limbic seizures, we also observed variable changes in firing rate in the midbrain reticular formation (MRF), with some seizures showing decreased firing and others no change (n = 9).
Conclusions: These preliminary results support the important role of the MRF in the modulation of consciousness during focal limbic seizures. Future investigations will include relating the firing of midbrain neurons to behavior and cortical physiological changes during and after seizures. In addition, this model will enable the detection of cell-specific signal changes with calcium imaging and neurotransmitter measurements with biosensors. Our study provides further evidence on the crucial role of subcortical arousal systems in seizures, which may serve as a novel therapeutic target for this disorder.
Funding: This work was supported by NIH R01 NS066974.
Basic Mechanisms