Authors :
Presenting Author: Francisco Javier Guevara Pantoja, PhD – University of California Riverside
Erfan Nozari, PhD – University of California, Riverside
Natalie Zlebnik, PhD – University of California, Riverside
Viji Santhakumar, PhD – University of California, Riverside
Rationale:
Temporal Lobe Epilepsy (TLE) is the most common seizure disorder, affecting about fifty million people worldwide. The dentate gyrus (DG), a crucial brain region in the hippocampus related to learning and memory, is strongly regulated by GABAergic inhibition from various interneuron (IN) subtypes, including soma-targeting parvalbumin- (PV+) INs and dendrite-targeting somatostatin (SST+) INs. Reorganization of DG circuitry, including IN loss, disrupts inhibitory control, which may influence seizure onset and termination. However, data on the specific roles of major IN subtypes in seizure onset and termination is limited. In this study, we investigated the specific roles of PV+ and SST+ IN in seizure onset and termination of acute and chronic epileptic mice.
Methods:
To investigate the roles of PV+ and SST+ INs, we induced AAV-driven Cre-dependent GCaMP expression in the DG of adult PV+ or SOM+ Cre mice. Three weeks after AAV injection, mice were implanted with an Optrode in the DG. Following a 5-7 day recovery period, mice were subjected to a Repeat Low Dose kainic acid (KA) protocol (5mg/kg every 20 min) to induce status epilepticus (SE). Photometry/EEG and video monitoring were conducted during acute seizure induction. Four weeks later, the chronic epileptic mice underwent photometry/EEG and video monitoring during KA-induced seizures. Recordings were performed using a custom-configured EEG, photometry, and video data recording system, enabling the correlation of local IN-specific calcium activity with EEG activity. A custom Python script compared calcium and Hilbert Burst Index (HBI) EEG signals.
Results:
During acute KA-induced seizures, PV+ INs exhibited a calcium peak signal 1.8 seconds (SD=27.9, n =5) after the HBI peak of EEG activity. In contrast, SST+ INs peaked 15 seconds (SD 27.8, n=5) after the EEG peak signal. However, this did not reach statistical significance (P >0.05, KSTest, N=5). In chronic epileptic mice, calcium peaks in PV-INs occurred 0.2 seconds (SD=29.4) before the HBI EEG peak. In comparison, calcium peaks in SST-INs occurred 4.5 seconds (SD=30.5) after the HBI peak (P >0.05, KSTest, N=5 ). Additionally, the calcium peak intensity in SST+ INs decreased significantly from 6.66 (SD=3.1) a.u (first induction) to 4.2 (SD=1.3) a.u in epileptic mice at 4 weeks (p< 0.05, KSTest, n=5, ), suggesting a loss of SST+ IN. In contrast, the calcium signal in PV+ INs during KA-induced seizures was not different between the two time points.