Potentiation of inhibition with perforant path kindling: an NMDA-receptor dependent process. 1991

M E Gilbert
Mantech Environmental Technology Incorporated, Research Triangle Park, NC 27709.

Kindling produces a long-lasting enhancement of excitatory and inhibitory neurotransmission. Both long-term potentiation and kindling-induced potentiation of hippocampal excitatory neurotransmission are suppressed by N-methyl-D-aspartate (NMDA) receptor antagonists. These antagonists also greatly retard the development of electrical kindling. We have previously reported prolonged afterdischarges (AD) in animals stimulated in the perforant path and treated with the NMDA antagonist, dizocilpine maleate (MK-801), despite a retardation in the development of kindling. In the present study the potentiation of excitation and inhibition was assessed during perforant path kindling when NMDA channels were blocked with MK-801. Paired pulse inhibition at 8 interpulse intervals (IPI 20-1000 ms) was monitored before and during kindling development. MK-801 (1 mg/kg, i.p.) delivered 30 min prior to perforant path stimulation increased AD thresholds and delayed kindling development. Potentiation of the excitatory postsynaptic potential (EPSP) and of paired pulse inhibition measured 20-24 h after each drug administration/stimulation were suppressed in MK-801-treated animals. Paradoxically, AD durations were prolonged by MK-801. Longer AD durations could be accounted for by a higher incidence of secondary AD bouts in MK-801 relative to control animals. Development of potentiation of the early phase of paired pulse inhibition (IPI 20-30 ms) was delayed and the potentiation of the late phase of inhibition (IPIs of 200-1000 ms) was completely blocked by MK-801. Thus, some of the enhancement of inhibition seen with kindling is dependent upon NMDA neurotransmission. Suppression of this potentiated inhibition may account for prolonged focal ADs in the perforant path and dentate gyrus.

UI MeSH Term Description Entries
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D008297 Male Males
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D005071 Evoked Potentials Electrical responses recorded from nerve, muscle, SENSORY RECEPTOR, or area of the CENTRAL NERVOUS SYSTEM following stimulation. They range from less than a microvolt to several microvolts. The evoked potential can be auditory (EVOKED POTENTIALS, AUDITORY), somatosensory (EVOKED POTENTIALS, SOMATOSENSORY), visual (EVOKED POTENTIALS, VISUAL), or motor (EVOKED POTENTIALS, MOTOR), or other modalities that have been reported. Event Related Potential,Event-Related Potentials,Evoked Potential,N100 Evoked Potential,P50 Evoked Potential,N1 Wave,N100 Evoked Potentials,N2 Wave,N200 Evoked Potentials,N3 Wave,N300 Evoked Potentials,N4 Wave,N400 Evoked Potentials,P2 Wave,P200 Evoked Potentials,P50 Evoked Potentials,P50 Wave,P600 Evoked Potentials,Potentials, Event-Related,Event Related Potentials,Event-Related Potential,Evoked Potential, N100,Evoked Potential, N200,Evoked Potential, N300,Evoked Potential, N400,Evoked Potential, P200,Evoked Potential, P50,Evoked Potential, P600,Evoked Potentials, N100,Evoked Potentials, N200,Evoked Potentials, N300,Evoked Potentials, N400,Evoked Potentials, P200,Evoked Potentials, P50,Evoked Potentials, P600,N1 Waves,N2 Waves,N200 Evoked Potential,N3 Waves,N300 Evoked Potential,N4 Waves,N400 Evoked Potential,P2 Waves,P200 Evoked Potential,P50 Waves,P600 Evoked Potential,Potential, Event Related,Potential, Event-Related,Potential, Evoked,Potentials, Event Related,Potentials, Evoked,Potentials, N400 Evoked,Related Potential, Event,Related Potentials, Event,Wave, N1,Wave, N2,Wave, N3,Wave, N4,Wave, P2,Wave, P50,Waves, N1,Waves, N2,Waves, N3,Waves, N4,Waves, P2,Waves, P50
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013569 Synapses Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions. Synapse
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D016291 Dizocilpine Maleate A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects. Dizocilpine,MK-801,MK 801,MK801
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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