Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol

In this study, we have investigated the developmental range over which diff erent stimulus protocols induce long-term depression (LTD). Low-frequency s timulation (LFS; 900 stimuli, 1 Hz) produced LTD in hippocampal slices from rats younger than similar to 40 days old, but not in animals aged between similar to 40 days and 16 weeks. We demonstrate, however, that different st imulus protocols can result in LTD in the adult hippocampus. Whilst one pai red-pulse low-frequency stimulus protocol [PP-LFS; 50 ms paired-pulse inter val (PPI), 900 pairs of stimuli] produced N-methyl-D-aspartate (NMDA) recep tor-independent LTD, another PP-LFS protocol (200 ms PPI; 900 pairs) produc ed NMDA receptor-dependent LTD. Furthermore, the saturation of NMDA recepto r-dependent LTD did not prevent the induction of further NMDA receptor-inde pendent LTD. This lack of occlusion suggests that different mechanisms of e xpression may underlie each of the above forms of LTD in the adult hippocam pus. In contrast to the adult hippocampus, NMDA receptor-dependent LTD was induced by both LFS and PP-LFS (50 ms PPI) in slices from young animals (12 -20 days). Although they share a common induction mechanism, LTD induced by PP-LFS may be expressed through other mechanisms in addition to those unde rlying LFS-induced LTD in the young hippocampus, In conclusion, the results in this study demonstrate that mechanisms of long-term synaptic depression within the hippocampus can alter radically with development of the central nervous system and with the use of different induction protocols.