Bidirectional modification of presynaptic neuronal excitability accompanying spike timing-dependent synaptic plasticity

Correlated pre- and postsynaptic activity that induces long-term potentiation is known to induce a persistent enhancement of the intrinsic excitability of the presynaptic neuron. Here we report that, associated with the induction of long-term depression in hippocampal cultures and in somatosensory cortical slices, there is also a persistent reduction in the excitability of the presynaptic neuron. This reduction requires postsynaptic Ca2+ elevation and presynaptic PKA- and PKC-dependent modification of slow-inactivating K+ channels. The bidirectional changes in neuronal excitability and synaptic efficacy exhibit identical requirements for the temporal order of pre- and postsynaptic activation but reflect two distinct aspects of activity-induced modification of neural circuits.