Weak excitation and simultaneous inhibition induce long-term depression in hippocampal CA1 neurons

1. Weak excitation to rat hippocampal CA1 neurons via Schaffer collaterals at a frequency of 0.1 or 0.2 Hz accompanied by repeated brief exposures to the inhibitory transmitter gamma-amino-butyric acid (GABA) causes a long-term depression (LTD, up to 90% of the control) of the stimulated pathway. This depression can be reversed by high-frequency stimulation. 2. Although inhibition is necessary for the induction of this LTD, the depression can be produced with either the GABAA or the GABAB receptor agonists. 3. This conjunctive LTD could not be blocked by the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric acid. 4. It was, however, blocked by the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, indicating that activation of a metabotropic glutamate receptor is necessary for the LTD. Induction also appeared to require an intracellular Ca2+ increase. 5. Because GABAergic inhibition often modulates glutamatergic transmission in the brain, we propose that this form of synaptic modification is of potential importance for neural plasticity.