Authors :
Presenting Author: Jayne Miner, BS – Vanderbilt University Medical Center
Gabi Barrocas, BS – Vanderbilt University Medical Center
Eunyoung Hong, BS – Vanderbilt University Medical Center
Yana Van den Abbeele, BS – Vanderbilt University Medical Center
William Nobis, MD, PhD – Vanderbilt University Medical Center
Rationale:
Odors have been used as epilepsy treatment for millennia, but the mechanisms by which olfactory pathways alter epilepsy remain unclear. While the olfactory cortex receives the majority of olfactory output, the amygdala also receives direct olfactory outputs. Our group has shown that spontaneous seizures activate extended amygdala (ExtA) neurons in a Dravet Syndrome (DS) mouse model (Scn1a+/-), and targeting this region can improve seizure-induced respiratory dysfunction and death in the audiogenic seizure (AGS) mouse DBA1.
Our goal was to determine if exposure to odors - 2-phenylethanol (2-PE) or lemon oil - can alter seizure frequency, severity, and mortality in DS and DBA1 models and begin to explore the effect on ExtA circuits. Our preliminary data suggest a bidirectional relationship between odorants on seizure severity and mortality, potentially based on their effect on ExtA neurons. We further explore the ability of these odorants to alter respiratory parameters and activity of the bed nucleus of the stria terminalis (BNST) neurons
Methods:
DS mice were exposed to 2-PE, lemon oil, or vehicle (water) odorant 8 hours a day for 15 days starting postnatal day 20/21. Respiratory parameters were measured before and after odor exposure using whole-body plethysmography. Mortality and seizure frequency were determined via continuous video monitoring. Seizure severity was determined using a modified Racine scale. Surviving 2-PE exposed mice had an extended washout period to determine the long-term effect of odorant exposure on mortality.
To examine circuit-level effects in the ExtA, DBA1 mice were primed to have repeated seizures and then were stereotaxically injected with AAV9-hSynGCamp6s into the BNST. After 15 days of odorant exposure, the mice were assessed for seizure type, latency, and severity. BNST slices were then imaged 24 hours later using single-photon calcium imaging
Results:
2-PE exposed DS mice showed decreased mortality (19.51%,n=41) compared to controls (35%, n=40; p=0.08). Lemon exposure increased mortality (62%, n=13, p< 0.05) and decreased survival when compared to vehicle (p< 0.05). DS mice exposed to 2-PE had more low-severity seizures (racine 1:p< 0.01; 3:p< 0.0001) and fewer high severity seizures (racine 6:p=0.03) than mice exposed to the vehicle. Analysis of seizure frequency and severity in lemon-oil exposed mice is ongoing.