Coincident spiking activity induces long-term changes in inhibition of neocortical pyramidal cells

In pyramidal cells, induction of long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission by coincidence of presynaptic and postsynaptic activity is considered relevant to learning processes in vivo. Here we show that temporally correlated spiking activity of a pyramidal cell and an inhibiting interneuron may cause LTD or LTP of unitary IPSPs. Polarity of change in synaptic efficacy depends on timing between Ca2+ influx induced by a backpropagating train of action potentials (APs) in pyramidal cell dendrites (10 APs, 50 Hz) and subsequent activation of inhibitory synapses. LTD of IPSPs was induced by synaptic activation in the vicinity of the AP train (<300 msec relative to the beginning of the train), whereas LTP of IPSPs was initiated with more remote synaptic activation (>400 msec relative to the beginning of the AP train). Solely AP trains induced neither LTP nor LTD. Both LTP and LTD were prevented by 5 mM BAPTA loaded into pyramidal cells. LTD was prevented by 5 mM EGTA, whereas EGTA failed to affect LTP. Synaptic plasticity was not dependent on activation of GABA(B) receptors. It was also not affected by the antagonists of vesicular exocytosis, botulinum toxin D, and GDP-beta -S.