Loss of CLOCK results in dysfunction of brain circuits that under | 50150

Journal of Neurology & Neurophysiology

ISSN - 2155-9562

Loss of CLOCK results in dysfunction of brain circuits that underlies pediatric focal epilepsy

Joint Event on International Conference on Neuroimmunology, Neurological disorders and Neurogenetics & 28th World Summit on Neurology, Neuroscience and Neuropharmacology

September 26-27, 2018 | Montreal, Canada

Peijun Li

The Second Affiliated Hospital of Wenzhou Medical University, China

Scientific Tracks Abstracts: J Neurol Neurophysiol

Abstract :

Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on the human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK we generated and tested the Emx- Cre; Clockflox/flox and PV-Cre; Clockflox/flox mouse lines with targeted deletions of the Clock gene in excitatory and parvalbumin (PV)-expressing inhibitory neurons, respectively. The Emx-Cre; Clockflox/flox mouse line alone has decreased seizure thresholds, but no laminar or dendritic defects in the cortex. However, excitatory neurons from the Emx-Cre; Clockflox/flox mouse have spontaneous epileptiform discharges. Both neurons from Emx-Cre; Clockflox/flox mouse and human epileptogenic tissue exhibit decreased spontaneous inhibitory post-synaptic currents. Finally, video-EEG of Emx-Cre; Clockflox/flox mice reveals epileptiform discharges during sleep and also seizures arising from sleep. Altogether, these data show disruption of CLOCK alters cortical circuits and may lead to the generation of focal epilepsy, which suggests that the circadian pathway may be a promising target for therapeutic intervention.

Biography :

Peijun Li received his PhD from the Department of Physiology and Biophysics, Georgetown University Medical Center. His research during his PhD study has been focusing on the inhibitory interneurons in mouse somatosensory cortex. During his postdoctoral work at Children’s National Medical Center at DC, he studied how hypoxia could affect the brain development using mouse model, and also how disruption in circadian gene expression could result in epilepsy in both human and mouse model. He is now a principal investigator at Second Affiliated Hospital, Wenzhou Medical University, China. As a scientist with expertise in electrophysiology, his work will be directed towards understanding the functional roles of specialized GABAergic inhibitory circuits in the pathophysiological process of epilepsy and circuit formation. In his free time, He likes running and listening to music. He has finished four half marathons and three full marathons which include the Marine Corps Marathon 2016 and the Rock and Roll DC 2016, His personal best is 3:53:25.