Long-term potentiation of high-frequency oscillation and synaptic transmission characterize in vitro NMDA receptor-dependent epileptogenesis in the hippocampus.
The implication of high-frequency network oscillations (HFOs) in brain pathology resides in as yet unclear mechanisms. Employing field recordings from ventral hippocampal slices and two models of epileptogenesis (i.e. establishment of interictal-like persistent bursts), we found that HFOs associated with epileptiform bursts and excitatory synaptic transmission were co-modulated during epileptogenesis. NMDA receptor-dependent epileptogenesis in CA3 was consistently accompanied by long-lasting strengthening in synaptic transmission (by 94+/-17%, n=5) and HFOs (frequency, power and duration increased by 24+/-8%, 57+/-18% and 33+/-10%, respectively). Co-modulation of synaptic transmission and HFOs was also observed in NMDA receptor-independent epileptogenesis, although in individual experiments either enhancement or depression of both phenomena was observed. Pathological HFOs >200 Hz were unequivocally present in persistent bursts induced by NMDA receptor-dependent but not NMDA receptor-independent mechanisms. The duration of pathological HFOs associated with persistent bursts but not of HFOs associated with bursts before the establishment of epileptogenesis was linearly and strongly correlated with the duration of bursts (r=0.58, P<0.0001). We propose that interplay between spontaneous synchronous bursting and long-lasting synaptic potentiation accompanying certain forms of epileptogenesis may underlie long-lasting potentiation of HFOs, whose quantitative aspects may reliably signal the degree of network changes involved in epileptogenesis.
Department of Physiology, Medical School, University of Patras, Rion, 26504, Greece.
Christos
C
Moschovos
George
G
Kostopoulos
Costas
C
Papatheodoropoulos
D000818:Animals; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000473:pathology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D018683:Excitatory Amino Acid Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D008274:Magnesium