Enhancement of presynaptic neuronal excitability by correlated presynaptic and postsynaptic spiking

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Use-dependent modifications, such as long-term potentiation (LTP) of synaptic efficacy, are believed to be essential for information storage in the nervous system. Repetitive correlated spiking of presynaptic and postsynaptic neurons can induce LTP at excitatory glutamatergic synapses. In cultured hippocampal neurons, we show that repetitive correlated activity also results in a rapid and persistent enhancement of presynaptic excitability, decreasing the threshold for spiking and reducing the variability of interspike intervals. Furthermore, we found that correlated activity modified sodium channel gating in the presynaptic neuron. This modification of presynaptic excitability required a temporal order between presynaptic and postsynaptic spiking and activation of postsynaptic NMDA receptors. Presynaptic inhibition of protein kinase C abolished the change in excitability without affecting LTP. Such rapid activity-dependent changes in the efficacy of presynaptic spiking may be involved in the processing and storage of information within the nervous system.

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Figure 1: Changes in neuronal firing properties induced by repetitive correlated activity.
Figure 2: Changes in presynaptic firing properties do not require synaptic transmission.
Figure 3: Correlated spiking lowers the spike threshold of the presynaptic neuron.
Figure 4: Changes in Na+ channel gating kinetics in the presynaptic neuron following correlated activity.
Figure 5: NMDA receptor activation and calcium influx into the postsynaptic neuron are required for the modification of presynaptic excitability by correlated spiking.
Figure 6: Dependence on the timing of presynaptic and postsynaptic spiking.
Figure 7: Correlated spiking at excitatory synapses made onto a GABAergic neuron does not modify presynaptic excitability.
Figure 8: Presynaptic PKC is required for induction of changes in presynaptic neuronal excitability, but not for the induction and expression of LTP.


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We thank B. Berninger, A.F. Schinder, G.-q. Bi, F. Engert and S. Andersen for discussion and comments on the manuscript, and X.-y. Wang for the preparation of cell cultures. This work was supported by a grant from NIH.

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Correspondence to Mu-ming Poo.

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