Multiunit Recording of the Locus Coeruleus and Behavioral Arrest During Focal Limbic Seizures in an Awake Mouse Model
Abstract number :
2.049
Submission category :
3. Neurophysiology / 3F. Animal Studies
Year :
2022
Submission ID :
2204084
Source :
www.aesnet.org
Presentation date :
12/4/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:23 AM
Authors :
Patrick Paszkowski, BS – Yale School of Medicine; Marcus Valcarce-Aspegren, BA – Yale School of Medicine; Shixin Liu, BS – Yale School of Medicine; Qian Wu, MD, PhD – Yale School of Medicine; Lim-Anna Sieu, PhD – Yale School of Medicine; Sarah McGil, BS – Yale School of Medicine; Hal Blumenfeld, MD, PhD – Yale School of Medicine
Rationale: In exploring the mechanisms behind impaired consciousness in temporal lobe epilepsy, rat models have highlighted brainstem and basal forebrain cholinergic neuron inhibition. To further explore other underlying pathways, multi-unit activity recordings in the locus coeruleus (LC) in an awake mouse model of focal limbic seizures can help us understand the role of noradrenergic modulation during ictal unconsciousness and related behavioral arrest.
Methods: We used a head-fixed mouse model with metal plates on a running-wheel apparatus. The animals had chronically implanted bipolar electrodes in the left orbitofrontal cortex (OFC) and bilateral hippocampi. Local field potentials were measured from electrodes in the hippocampi while focal limbic seizures were induced through 2 s 60 Hz pulses sent to the hippocampus. LC neurons were recorded with a high-impedance, tungsten microelectrode (2-4 MΩ resistance; FHC), and placement was later confirmed histologically with DiI. The LC was visualized using anti-tyrosine hydroxylase fluorescent staining. Statistical analysis of LC multiunit activity, wheel rotation to speed conversion, and plotting was performed in MATLAB.
Results: The triggering of focal limbic seizures in the mice led to behavioral arrest with concomitant decreases in LC multiunit activity. More specifically, we compared average normalized LC multiunit activity (quantified as Vrms) using paired t-tests between pre-ictal and ictal epochs and found significant decreases in firing rate (n = 8, p < 0.05). Behaviorally, motor activity quantified as wheel speed (cm/s), similarly showed a significant decrease during seizures, and often complete behavioral arrest, in ictal epochs. Average wheel speed for pre-ictal was 30.1 ± 6.9 cm/s, and for ictal was 3.3 ± 1.4 cm/s (p < 0.01).
Neurophysiology