Asymptotic hippocampal long-term potentiation in rats does not preclude additional potentiation at later phases

Hippocampal long-term potentiation may serve as an elementary process underlying certain forms of learning and memory in vertebrates. As is the case with behavioural memory, hippocampal long-term potentiation in the CA1 region and in the dentate gyrus exhibits distinct phases. These comprise a short-term early potentiation which lasts one to three hours and is independent of protein synthesis and is characterized in general by the activation of N-methyl-D-aspartate receptors and protein kinases; and a later, longer lasting phase, which can be separated by inhibitors of protein synthesis. Here, we report that the prior induction of long-term potentiation, both in the dentate gyrus in vivo and in the CA1-region in vitro, precludes further long-term but not short-term potentiation by means of a newly delivered conditioning stimulus to a subset of the same activated synapse population during the early stage (approximately 1-3 hours post tetanus). In contrast, a subsequent, long-lasting potentiation can be induced after the establishment of the late phase of potentiation (> 4 h). Thus, the system preserves the capacity for short-term potentiation immediately after potentiation, but the capacity for the induction of longer lasting plastic changes is recovered only after about four hours. Our results demonstrate that, once long-term potentiation has been established, hippocampal neurons do not lose their capacity for functional plasticity during certain phases of the maintenance of long-term potentiation.