Abstracts

Rationale: Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Optogenetics is a powerful tool to enables precise control of neural activity with high spatial and temporal resolutions. We investigated optogenetic neuromodulations targeting the hippocampal network to generate seizure-like events (SLEs) and verify the effects on neural activities in a TLE rat model.

Methods: TLE rat model was induced by intrahippocampal microinjection of kainic acid. For optogenetic induction of SLEs, CAMKII neurons were targeted for ChR2 expression in hippocampus. 1.5µl AAV5-CaMKIIa-hChR2-EYFP injected into the right hippocampus (ML: +3.2 mm, AP: -4.56 mm, DV: -3.8 mm from bregma). After 6 weeks, optical fiber and local field potential (LFP) microelectrodes were implanted and a 473 nm blue-light was delivered with 200 pulse trains at 40 Hz for 5s duration, starting at 80 mW/mm² intensity. To find appropriate parameter thresholds for SLE generation, light intensity was gradually increased in steps every 2 minutes. We assessed dynamic alterations of neural activities between baseline and SLE after light stimulation in different frequency bands including delta (2-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), gamma (30-80 Hz), ripple (80-250 Hz), fast ripple (250-500 Hz), and ultra-fast ripple (500-1000 Hz) by calculating the power spectral density (PSD) value that reflects the power of the LFP signals.

Results:

To induce SLEs, CaMKII-positive excitatory neurons in the hippocampus were optogenetically stimulated. A mean light power of 353 mW/mm² was required for induction of SLEs and epileptiform activity. We observed two different types of SLE pattern such as fast activity and repetitive spike with slow waves(figure). Compared to baseline recording, we analyzed the changes of neural dynamics of SLE that increased PSD value of beta and gamma and decreased PSD value of fast ripple and ultra-fast ripple (PSD values: beta_baseline = 20.257dB vs. beta_stimulation = 47.516dB (p<