Bi-Directional Modification Of Presynaptic Neuronal Excitability Accompanying Spike Timing-Dependent Synaptic Plasticity

Synaptic plasticity is thought to be important for learning and memory, and activity-dependent circuit rewiring. However, neuronal properties other than synaptic strength can be modulated by neuronal activity. 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. The question is whether there is correlation between synaptic depression and modification of global excitability. Using paired patch-recording, 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 via L-type Ca2+ channel and Ca2+ released from intracellular stores, and presynaptic PKA- and PKC-dependent modification of slow-inactivating K+ channels. The bi-directional 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. Such activity-dependent bi-directional modification of global excitability may play important roles in information processing in neural circuits.