Homeostatic plasticity induced by brief activity deprivation enhances long-term potentiation in the mature rat hippocampus.

Different forms of plasticity occur concomitantly in the nervous system. Whereas homeostatic plasticity monitors and maintains neuronal activity within a functional range, Hebbian changes such as long-term potentiation (LTP) modify the relative strength of specific synapses after discrete changes in activity and are thought to provide the cellular basis for learning and memory. Here, we assessed whether homeostatic plasticity could influence subsequent LTP in acute hippocampal slices that had been briefly deprived of activity by blocking action potential generation and N-methyl-D-aspartate (NMDA) receptor activation for 3 h. Activity deprivation enhanced the frequency and the amplitude of spontaneous miniature excitatory postsynaptic currents and enhanced basal synaptic transmission in the absence of significant changes in intrinsic excitability. Changes in the threshold for Hebbian plasticity were evaluated by inducing LTP with stimulation protocols of increasing strength. We found that activity-deprived slices consistently showed higher LTP magnitude compared with control conditions even when using subthreshold theta-burst stimulation. Enhanced LTP in activity-deprived slices was also observed when picrotoxin was used to prevent the modulation of GABAergic transmission. Finally, we observed that consecutive LTP inductions attained a higher magnitude of facilitation in activity-deprived slices, suggesting that the homeostatic plasticity mechanisms triggered by a brief period of neuronal silencing can both lower the threshold and raise the ceiling for Hebbian modifications. We conclude that even brief periods of altered activity are able to shape subsequent synaptic transmission and Hebbian plasticity in fully developed hippocampal circuits.