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J Neurophysiol. 1994 Jul;72(1):72-83.

Long-term changes in neocortical activity after chemical kindling with systemic pentylenetetrazole: an in vitro study.

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Department of Physiology, Ben-Gurion University of the Negev, Beersheva, Israel.


1. Rats were chemically kindled by systemic administration of pentylenetetrazole (PTZ) every 48 h. An initially subthreshold dose that did not elicit a motor response when first applied caused severe epileptiform seizures when the animal was kindled. Once kindled, animals continued to respond to the initially subthreshold dose with a full-blown seizure for > 2 mo, even when regular administration ceased for > or = 1 mo. 2. In neocortical slices taken from kindled rats, low-intensity electrical stimulation evoked generation of prolonged (hundreds of milliseconds) paroxysmal extracellular field potentials and intracellular depolarizing potentials, indicating synchronized activity of large populations of neurons. This hyperexcitability usually appeared as an all-or-none event of variable latency. In a few cases it increased gradually with increasing stimulus intensity. The intensity of the paroxysmal response was greatly enhanced by application of gamma-aminobutyric acid-A (GABAa) receptor blockers to the bath. 3. Intracellular recordings revealed that PTZ-kindled cells differ from normal cells in their higher input resistance (42.4 + 13.6 vs. 26.4 + 9.2 M omega, mean +/- SE). Spikes generated by kindled cells differed significantly from those in normal cells in that they were of longer duration (1.65 + 0.3 vs. 1.40 + 0.15 ms) and had a slower maximal rate of fall (103 + 29.7 vs. 126 + 20.8 volts/s). 4. Injection of the lidocaine derivative QX-314 to the recorded neurons (100 mM) blocked the fast Na+ spikes. Under these conditions slow spikes, probably Ca2+ mediated, were evoked from the soma in neurons from kindled but not from normal cortex. 5. The role of N-methyl-D-aspartate (NMDA) receptors in generating paroxysmal events was evaluated by application of 20 microM 2-amino-5-phosphonovaleric acid, a specific blocker of this glutamate receptor type. Blockage of NMDA receptors cut short the paroxysmal field potentials but did not prevent their generation. Intracellularly recorded paroxysmal responses were also cut short but not abolished by intracellular hyperpolarization. 6. In slices from kindled animals intracellular responses in neurons of deeper layers differed markedly from those of superficial cells. In deep neurons, responses resembled those generated by neocortical neurons exposed to GABAergic blockers. A low-intensity stimulus to the white matter evoked an excitatory postsynaptic potential (EPSP) followed with variable latency by a paroxysmal depolarizing shift that reversed at suprathreshold membrane potentials and on which superimposed repetitive firing was always evident.(ABSTRACT TRUNCATED AT 400 WORDS)

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