WEAK EXCITATION AND SIMULTANEOUS INHIBITION INDUCE LONG-TERM DEPRESSION IN HIPPOCAMPAL CA1 NEURONS

Weak excitation to rat hippocampal CA1 neurons via Schaffer collateral s at a frequency of 0.1 or 0.2 Hz accompanied by repeated brief exposu res to the inhibitory transmitter gamma-amino-butyric acid (GABA) caus es a long-term depression (LTD, up to 90% of the control) of the stimu lated pathway. This depression can be reversed by high-frequency stimu lation. Although inhibition is necessary for the induction of this LTD , the depression can be produced with either the GABA, or the GABA(B) receptor agonists. This conjunctive LTD could not be blocked by the N- methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric aci d. It was, however, blocked by the metabotropic glutamate receptor ant agonist L-2-amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-ca rboxyphenylglycine indicating that activation of a metabotropic glutam ate receptor is necessary for the LTD. Induction also appeared to requ ire an intracellular Ca2+ increase.Because GABAergic inhibition often modulates glutamatergic transmission in the brain, we propose that thi s form of synaptic modification is of potential importance for neural plasticity.