Enhancement of presynaptic neuronal excitability by correlated presynapticand postsynaptic spiking

Use-dependent modifications, such as long-term potentiation (LTP) of synapt ic efficacy, are believed to be essential for information storage in the ne rvous system. Repetitive correlated spiking of presynaptic and postsynaptic neurons can induce LTP at excitatory glutamatergic synapses. In cultured h ippocampal neurons, we show that repetitive correlated activity also result s in a rapid and persistent enhancement of presynaptic excitability, decrea sing the threshold for spiking and reducing the variability of interspike i ntervals. Furthermore, we found that correlated activity modified sodium ch annel gating in the presynaptic neuron. This modification of presynaptic ex citability required a temporal order between presynaptic and postsynaptic s piking and activation of postsynaptic NMDA receptors. Presynaptic inhibitio n of protein kinase C abolished the change in excitability without affectin g LTP. Such rapid activity-dependent changes in the efficacy of presynaptic spiking may be involved in the processing and storage of information withi n the nervous system.