Juxtacellular Recording of Noradrenergic Activity in the Locus Coeruleus in an Awake Mouse Temporal Lobe Seizure Model
Abstract number :
1.037
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2021
Submission ID :
1825660
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:44 AM
Authors :
Marcus Valcarce-Aspegren, BA - Yale School of Medicine; Qian Wu, MD, PhD - Yale School of Medicine; Lim-Anna Sieu, PhD - Yale School of Medicine; Patrick Paszkowski, - - Yale School of Medicine; Abdelrahman Sharafeldin, BS - Yale School of Medicine; Alvaro Duque, PhD - Yale School of Medicine; Hal Blumenfeld, MD, PhD - Yale School of Medicine
Rationale: Previous studies in rat models have identified the inhibition of brainstem and basal forebrain cholinergic neurons as potential drivers of depressed arousal during temporal lobe epilepsy (TLE). However, much of the subcortical pathway affecting seizure-related depressions in cortical function remains unknown. Using an awake mouse model to record single-cell activity in the locus coeruleus in a temporal lobe seizure model may clarify the role of subcortical noradrenergic modulation during the ictal period. Additionally, showing that the juxtacellular recording-method is viable for investigating individual neurons deep in the brainstems of awake, moving mice can open the door to the targeted study of other subcortical regions of interest.
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 (2s, 60 Hz) into the hippocampus. We used 1.5mm glass capillaries filled with 4% Neurobiotin to record and identify noradrenergic neurons in the locus coeruleus by double staining with cy3-streptavidin and anti-tyrosine hydroxylase antibodies.
Results: Recordings from the locus coeruleus demonstrated that it was possible to find and maintain a stable single-cell signal deep in the brainstem of moving animals (n=9). Additionally, preliminary data showed a decrease in firing frequency and changes to firing patterns of individual locus coeruleus neurons during periods of focal hippocampal seizures (n=2 animals). Neurons in the locus coeruleus were successfully identified by histology.
Conclusions: These early results suggest that stable juxtacellular recording of individual neurons in the deep brainstem is possible in awake, moving mice during seizures. Additionally, the modulation of neurons in the locus coeruleus appears to play a potential role in the modulation of arousal during focal limbic seizures. Further investigation of specific subcortical neurons and neurotransmitters affected during seizures is critical in uncovering the mechanisms underlying ictal unconsciousness and may lead to novel, improved treatments for people with epilepsy.
Funding: Please list any funding that was received in support of this abstract.: NIH R01 NS066974
James G. Hirsch, M.D. Endowed Medical Student Research Fellowship.
Basic Mechanisms