Single-Neuron Discharges Correlating High-Frequency Oscillations Dynamics in Epileptogenesis and Epilepsy Development

The mechanism of epilepsy is still unclear. We aim to explore the relationship between high-frequency oscillations (HFOs) dynamics and epilepsy, with a focus on deciphering underlying mechanisms at the single-neuron level. Using a rat model of chronic focal cortical epilepsy induced by cobalt-wire implantation, we monitored the seizures and HFO dynamics, as well as the cross-frequency coupling trends between HFOs and theta activities. Additionally, excitatory and inhibitory neurons' discharges were recorded by 16-channel tetrode electrode, with comparisons made between the discharge rates and changes from baselines during different bands of HFOs (ripple:80-200 Hz; fast ripple, FRs:200-500 Hz). All rats (8/8) with cobalt-wire implantation developed spontaneous seizures within 4 to 8 days post-surgery, in contrast to the control group (3/3) with steel-wire insertion remaining seizure-free. HFOs exhibited a progressive increase over time post-surgery in the epilepsy model, while minimal HFOs was observed in the control group. HFOs recorded during the peak-seizure periods showed a propensity to synchronize with the trough of theta activity, coinciding with heightened seizure frequency. A substantial augmentation showed in the discharge rates of both putative excitatory and inhibitory neurons during HFO occurrences. The change ratios between putative excitatory and inhibitory neurons during ripples were smaller than those during FRs. In conclusion, we found that HFO dynamics reflect epileptogenic network formation, with implications for early seizure prediction and therapeutic interventions. Our data provide novel insights at cellular and cross-frequency level into the mechanistic underpinnings of HFO emergence and network reorganization offering potential strategies for targeting pathological network activity in epilepsy.