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. Lo ng-term potentiation (LTP) and depotentiation (DP) of synaptic transmi ssion have been suggested to model memory formation at the neuronal le vel. Recently it was shown that LTP in the dentate gyrus or area CA3 o f 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 impa ired spatial learning in a water maze or radial arm maze (three out of eight arms baited) when injected ICV (5 mu l of a 20 mM solution). Th ere also were small impairments in non-spatial and visual discriminati on tasks, indicating that the small learning impairments were due to n onselective effects of the drug. The same dose depressed field EPSPs a nd completely blocked LTP induced by high-frequency stimulation (HFS, 200 Hz) in the CA1 region of the rat hippocampus in vivo. A lower (5 m u l of a 10 mM solution) dose did not depress baseline but still block ed LTP. Injecting the same dose after induction of LTP blocked DP indu ced by low-frequency stimulation (LFS, 10 Hz). These results indicate that neither HFS-induced LTP nor LFS-induced DP in area CA1 are good m odels for the induction of synaptic changes that might underlie spatia l learning in the rat.