Long-Term Synaptic Transformation of Hippocampal CA1 γ-Aminobutyric Acid Synapses and the Effect of Anandamide

Evidence is presented for a distinctive type of hippocampal synaptic modification [previously described for a molluscan γ-aminobutyric acid (GABA) synapse after paired pre- and postsynaptic excitation]: transformation of GABA-mediated synaptic inhibition into synaptic excitation. This transformation persists with no further paired stimulation for 60 min or longer and is termed long-term transformation. Long-term transformation is shown to contribute to pairing-induced long-term potentiation but not to long-term potentiation induced by presynaptic stimulation alone. Further support for such mechanistic divergence is provided by pharmacologic effects on long-term transformation as well as these two forms of long-term potentiation by Cl-channel blockers, glutamate and GABA antagonists, as well as the endogenous cannabinoid ligand anandamide.