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Synaptic activity modulates presynaptic excitability

Abstract

Synaptic activity modulates synaptic efficacy and is important in learning and development. Here we show that development of excitability in presynaptic motor neurons required synaptic activation of postsynaptic muscle cells. Synaptic blockade broadened action potentials and decreased repetitive firing of presynaptic neurons. Consistent with these findings, synaptic blockade also decreased potassium-current density in the presynaptic cell. Application of neurotrophin-3, but not related neurotrophins, prevented these changes. Recordings from patches of somatic membrane indicated that modifications of presynaptic potassium and sodium currents occurred in a remote, nonsynaptic compartment. Thus, activity-dependent postsynaptic signals modulated presynaptic excitability, potentially regulating transmission at all synapses of the presynaptic cell.

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Figure 1: Neurons with NMJs had shorter-duration action potentials than other neurons.
Figure 2: Neurons with NMJs showed enhanced ability to fire repetitively.
Figure 3: Chronic synaptic blockade with α-BgTx induced broadening of action potentials that was prevented with neurotrophin-3.
Figure 4: Synaptic blockade reduced the ability to fire repetitively, whereas co-application of NT-3 increased repetitive-firing capacity to control levels.
Figure 5: Decreases in delayed-rectifier IK density induced by synaptic blockade were prevented by co-application of NT-3, but not other neurotrophins.
Figure 6: α-BgTx and NT-3 shifted the voltage dependence of activation of IK.
Figure 7: G–V relation of IK shifted in response to α-BgTx in macropatches pulled from the somata of neurons as in whole-cell recordings.
Figure 8: The G–V relation of INa in macropatches pulled from the neuronal soma showed an α-BgTx-induced shift.

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Acknowledgements

We thank W. J. Betz, J. W. Karpen, J. L. Lubischer, T. C. Rich, K. R. Svoboda and B. G. Wallace for reading the manuscript; and B. Lu, T. J. Carew, L. K. Kaczmarek and M.-M. Poo for comments and suggestions. This work was supported by NIH grants to T.A.N. and A.B.R.

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Correspondence to Teresa A. Nick.

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Nick, T., Ribera, A. Synaptic activity modulates presynaptic excitability. Nat Neurosci 3, 142–149 (2000). https://doi.org/10.1038/72082

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