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

Neuron. 2004 Jan 22;41(2):257-68. doi: 10.1016/s0896-6273(03)00847-x.


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 Ca(2+) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / physiology
  • Calcium Signaling / physiology
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiology
  • Cyclic AMP-Dependent Protein Kinases / physiology
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / physiology
  • In Vitro Techniques
  • Long-Term Potentiation / physiology
  • Membrane Potentials / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Patch-Clamp Techniques
  • Potassium Channels / physiology
  • Protein Kinase C / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Presynaptic / physiology*
  • Somatosensory Cortex / cytology
  • Somatosensory Cortex / physiology
  • Synapses / physiology*


  • Potassium Channels
  • Receptors, Presynaptic
  • Cyclic AMP-Dependent Protein Kinases
  • Protein Kinase C
  • Calcium