Activation of inhibitory pathways suppresses the induction of long-term potentiation in neurons of the rat lateral septal nucleus.
Long-term potentiation of the hippocampal-septal pathway was examined by intracellular recording techniques. High frequency stimulation (two 100-Hz 1-s trains with a 20-s interval between them) of the hippocampal CA3 area resulted in a transient depolarization in rat lateral septal nucleus neurons. High frequency stimulation was followed by a facilitation of fast and slow inhibitory postsynaptic potentials, lasting for more than 2 h, but not by a long-lasting increase in the excitatory postsynaptic potential in the normal solution. Long-term potentiation (>2 h) of the excitatory postsynaptic potential did not appear in 74% of neurons tested, even when the fast inhibitory postsynaptic potential was blocked by bicuculline (30 microM), a GABA(A) receptor antagonist. High frequency stimulation produced long-term potentiation of the excitatory postsynaptic potential in the Mg(2+)-free solution containing bicuculline. When the fast and slow inhibitory postsynaptic potentials were blocked by GABA(A) and GABA(B) receptor antagonists (bicuculline and CGP 55845A respectively), high frequency stimulation produced a large and sustained depolarization followed by long-term potentiation of the excitatory postsynaptic potential. However, the excitatory postsynaptic potential was not enhanced by administration of these drugs after termination of high frequency stimulation. Pretreatment with 2-amino-5-phosphonopentanoate, a NMDA receptor antagonist, resulted in loss of long-term potentiation in both sets of experiments. Paired-pulse stimulation of the hippocampal CA3 region with interstimulus intervals between 200 and 800 ms depressed the second excitatory postsynaptic potential in the presence of bicuculline. CGP 35348, a GABA(B) receptor antagonist, reversed the depression of excitatory postsynaptic potentials to facilitation. These data suggest that high frequency stimulation of hippocampal CA3 neurons enhances the efficacy of GABAergic inhibitory circuits which, in turn, depress the ability of lateral septal nucleus neurons to express long-term potentiation.
Hasuo
H
H
Department of Physiology, Kurume University School of Medicine, 67 Asahi-machi, 830-0011, Kurume, Japan.
Akasu
T
T
D000818:Animals; D002586:Cesium / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D020712:Fornix, Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008275:Magnesium Deficiency / Q000378:metabolism; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism; D012686:Septal Nuclei / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D018080:Receptors, GABA-B; D002586:Cesium; D005680:gamma-Aminobutyric Acid