The role of chloride-dependent inhibition and the activity of fast-spiking neurons during cortical spike-wave electrographic seizures.
The conventional view is that the cortical paroxysmal depolarizing shift is a giant excitatory postsynaptic potential enhanced by various intrinsic neuronal currents. Other results point out, however, that synaptic inhibition remains functional in many forms of paroxysmal activities and that intense activation of GABAergic interneurons may accentuate the excitation of target pyramidal cells. To determine the role played by cortical inhibitory neurons in paroxysmal discharges, we used single and dual intracellular recordings from electrophysiologically identified neocortical neurons during spontaneously occurring and electrically induced spike-wave electrographic seizures in vivo. Conventional fast-spiking neurons (presumably local inhibitory interneurons) fired at a very high frequency during paroxysmal depolarizing shifts, which corresponded to the electroencephalogram 'spike' components of spike-wave complexes. The firing of fast-spiking neurons preceded the discharges of neighboring regular-spiking neurons. During electrographic seizures, the reversal potential of the GABA (type A)-mediated potentials in regular-spiking neurons was shifted to positive values by 20-30 mV. Data also show that the prolonged hyperpolarizations during the electroencephalogram 'wave' components of spike-wave electrographic seizures do not contain Cl(-)-dependent inhibitory potentials. Moreover, Cl(-)-dependent mechanisms were reduced or absent during the fast runs that are associated with spike-wave complexes in some paroxysms. We conclude that the strong activity of cortical inhibitory neurons during paroxysmal depolarizing shifts induces Cl(-)-dependent depolarizing postsynaptic potentials in target pyramidal neurons, which facilitate the development of electrographic seizures.
Timofeev
I
I
Laboratoire de Neurophysiologie, Faculté de Médecine, Université Laval, Québec, QC, Canada G1K 7P4. igor.timofeev@phs.ulaval.ca
Grenier
F
F
Steriade
M
M
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000503:physiopathology*; D002712:Chlorides / Q000502:physiology*; D017097:Electric Impedance; D004827:Epilepsy / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002712:Chlorides; D005680:gamma-Aminobutyric Acid