Increase in [3H]glutamate release from slices of dentate gyrus and hippocampus following classical conditioning in the rat.

The release of amino acids was examined in three hippocampal areas following classical conditioning. Paired or unpaired tone(CS)-shock(US) presentations were given to animals engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever-pressing was the behavioural measure of conditioning. The dentate gyrus and areas CA1 and CA3 of the hippocampus were removed bilaterally from conditioned and pseudoconditioned animals, and slices cut and stored in liquid nitrogen for subsequent in vitro analysis of the release of radiolabelled glutamate and aspartate. K+-stimulated release of radiolabelled amino acids was analysed in the presence and absence of extracellular Ca2+. Potassium-stimulated, Ca2+-dependent release of [3H]glutamate was significantly greater in slices of dentate gyrus and area CA1 prepared from conditioned animals than from pseudoconditioned animals. This finding identifies a neurochemical change associated with classical conditioning which is similar to the increase in transmitter release seen in hippocampal long-term potentiation (LTP), and which is consistent with the hypothesis that an LTP-like mechanism is involved in mnemonic processes.