A novel mouse model of focal limbic seizures with impaired behavior and cortical slow waves
Abstract number :
462
Submission category :
2. Translational Research / 2D. Models
Year :
2020
Submission ID :
2422804
Source :
www.aesnet.org
Presentation date :
12/6/2020 5:16:48 PM
Published date :
Nov 21, 2020, 02:24 AM
Authors :
Lim-Anna Sieu, Yale University; Shobhit Singla - Yale University; Ganesh Chandrasekaran - Yale University; Abdo Sharaf - Yale University; Abhijeet Gummadavelli - Yale University; Reese Martin - Yale University; Cian McCafferty - University College Cork; M
Rationale:
Patients with focal temporal lobe seizures associated with loss of consciousness are positively correlated with EEG neocortical slow waves, similar to the non-REM sleep state. Previous work in a rat model of focal limbic seizures suggests that decreased activity of subcortical arousal systems, including brainstem and basal forebrain cholinergic neurons, cause depressed cortical function during seizure. However, a mouse model provides more genetics tools available for investigation of specific cellular and network mechanisms.
Method:
Water-restricted mice were head-fixed on a running wheel and trained to lick a spout in response to a sound (0-50kHz noise, 12ms) every 10-15s. Local field potential activity was recorded in the right orbitofrontal cortex (OFC) and in the hippocampus (HC) via implanted bipolar electrodes. Focal limbic seizures were induced through the HC electrode with a 2s, 60 Hz current injection. Multiunit activity (MUA) was recorded in left OFC via an additional tungsten electrode.
Results:
Induced focal seizures were of 5-30s duration, repeatable for several weeks (n=20 animals).
Behavioral responses showed a decrease of lick rate to sound, as well as running speed, during seizure (p< 0.01, n=20 animals). Licking response to sound could vary from being impaired to normal during seizure. By examining licking response and cortical activity, we found that behavioral impairment is correlated with large amplitude cortical slow-wave activity, as seen in patients with temporal lobe seizures. Moreover, the cortical slow waves showed a pattern of MUA similar to Up and Down states observed during the slow wave sleep state (n=6 animals).
Conclusion:
These results suggest that induced focal limbic seizures in the mouse can impair consciousness associated with depressed cortical function resembling slow wave sleep. Thus, this novel mouse model has similar characteristics with the rat model and human temporal lobe seizure and may be used to uncover the fundamental mechanisms for loss of consciousness in focal seizures. Future work with this model may lead to innovative treatment approaches for this common disorder.
Funding:
:NIH R01 NS066974 and R01 NS096088
Translational Research