Enhancement of paired-pulse depression in the dentate gyrus in vivo by the NMDA antagonist, MK-801, and electrical kindling.
We have previously demonstrated that late paired-pulse depression of dentate granule cell field potentials decreases when stimulus intensity is increased from moderate to high levels. Voltage-dependent N-methyl-D-aspartate (NMDA) currents are increasingly activated within this stimulus range, and are enhanced following the development of kindled seizures. The NMDA antagonist, MK-801 (0.25 and 1.0 mg/kg, i.p.), was used in the present experiments to evaluate the contribution of NMDA currents to the loss of late paired-pulse depression at high stimulus intensities in naive and kindled rats. Paired-pulse stimulus intensity functions were obtained from animals prepared with chronic electrodes in the perforant path and dentate gyrus. MK-801 administration had no effect on the stimulus intensity function for early paired-pulse depression (20-30 ms interpulse intervals, IPI) in either preparation. Late paired-pulse depression (150-500 ms IPI) was significantly enhanced in naive rats by MK-801. In contrast, MK-801 had no effect on the potentiation of late paired-pulse depression recorded from kindled animals. These findings suggest that the ability of NMDA currents to reduce the strength of late paired-pulse depression in naive animals is altered following the development of kindled seizures. A decrease in late paired-pulse depression was observed at high stimulus intensities under all experimental conditions. The latter findings indicate that the processes responsible for the reduction in late paired-pulse depression at high stimulus intensities are unaffected by either NMDA or kindling-induced modulation of late paired-pulse depression.
National Research Council, Research Triangle Park, NC 27711, USA. gilbert@herl45.herl.epa.gov
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D000818:Animals; D013181:Cortical Spreading Depression; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007839:Functional Laterality; D007696:Kindling, Neurologic; D008297:Male; D051381:Rats; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate