HFS-induced long-term potentiation and LFS-induced depotentiation in area CA1 of the hippocampus are not good models for learning.

Spatial learning in rats has been shown to be dependent on the intact hippocampus and lesioning this region impairs learning performance. Long-term potentiation (LTP) and depotentiation (DP) of synaptic transmission have been suggested to model memory formation at the neuronal level. Recently it was shown that LTP in the dentate gyrus or area CA3 of the hippocampus is not essential for the ability to learn a spatial water maze task. Here we show that the metabotropic glutamate receptor agonist (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3S-ACPD), which acts predominantly at presynaptic sites, only marginally impaired spatial learning in a water maze or radial arm maze (three out of eight arms baited) when injected ICV (5 microliters of a 20 mM solution). There also were small impairments in non-spatial and visual discrimination tasks, indicating that the small learning impairments were due to nonselective effects of the drug. The same dose depressed field EPSPs and completely blocked LTP induced by high-frequency stimulation (HFS, 200 Hz) in the CA1 region of the rat hippocampus in vivo. A lower (5 microliters of a 10 mM solution) dose did not depress baseline but still blocked LTP. Injecting the same dose after induction of LTP blocked DP induced by low-frequency stimulation (LFS, 10 Hz). These results indicate that neither HFS-induced LTP nor LFS-induced DP in area CA1 are good models for the induction of synaptic changes that might underlie spatial learning in the rat.