Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid.
1. The action of a short bath application of kainic acid (KA, 200-250 nM, 3-5 min) on the CA3 region of rat hippocampal slices has been studied with intracellular and extracellular recording techniques. 2. KA evoked bursts which persisted for 10-15 min. In addition, after KA, electrical stimulation of various inputs to CA3 which elicited an EPSP-IPSP sequence in control conditions evoked an EPSP followed by a burst. This evoked response persisted for several hours after removal of KA suggesting the occurrence of a long-lasting modification of the synaptic properties of CA3 neurones. 3. Intracellular recordings showed the spontaneous and evoked bursts to consist of five to ten action potentials riding on a depolarizing shift 10-25 mV in amplitude and 40-100 ms in duration. Both spontaneous and evoked bursts were followed by a long-lasting hyperpolarization 15-25 mV in amplitude and 1-1.5 s in duration. 4. We propose that both spontaneous and evoked synchronized bursts are generated by a polysynaptic network since: (a) intracellularly recorded bursts were synchronized with the bursts in extracellular field recording; (b) bursts disappeared when synaptic transmission or Na+ action potential were blocked by cobalt (1 mM) or TTX (1 microM) respectively; (c) bursts were suppressed by elevated divalent cation concentration; (d) burst occurrence was independent of the membrane potential of the cell; (e) the depolarization shift that underlies the bursts was a linear function of the membrane potential and reversed in polarity at 0 mV. In addition, the evoked bursts were all-or-none events with a variable latency. 5. Laminar profile analysis of the spontaneous and evoked bursts suggests that they were generated by synapses located on the distal apical segments of the dendrites of CA3 pyramidal cells. 7. The persistence of the evoked bursts was neither due to a persistent change in cell excitability nor to a long-lasting reduction in GABAergic synaptic inhibition. 8. Bath application of a high concentration of potassium (7 mM) also induced spontaneous and evoked bursts; the latter also persisted several hours after return to control medium. 9. The N-methyl-D-aspartate (NMDA) antagonist, D-APV (D(-)-2-amino-5-phosphonovaleric acid) (30 microM), did not block the spontaneous discharges induced by KA or high potassium, but prevented the long-lasting effects on the synaptic responses.(ABSTRACT TRUNCATED AT 400 WORDS)
Ben-Ari
Y
Y
Unité 29, INSERM, Paris, France.
Gho
M
M
D015763:2-Amino-5-phosphonovalerate; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D014633:Valine; D008274:Magnesium; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium