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Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics

Abstract

The output of a neural circuit results from an interaction between the intrinsic properties of neurons in the circuit and the features of the synaptic connections between them. The plasticity of intrinsic properties has been primarily attributed to modification of ion channel function and/or number. We have found a mechanism for intrinsic plasticity in rhythmically active Drosophila neurons that was not based on changes in ion conductance. Larval motor neurons had a long-lasting, sodium-dependent afterhyperpolarization (AHP) following bursts of action potentials that was mediated by the electrogenic activity of Na+/K+ ATPase. This AHP persisted for multiple seconds following volleys of action potentials and was able to function as a pattern-insensitive integrator of spike number that was independent of external calcium. This current also interacted with endogenous Shal K+ conductances to modulate spike timing for multiple seconds following rhythmic activity, providing a cellular memory of network activity on a behaviorally relevant timescale.

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Figure 1: Dorsal motor neurons in third instar larvae have a long-lasting, Na+-dependent AHP following volleys of action potentials.
Figure 2: The larval AHP has electrophysiological and pharmacological features of a Na+/K+ pump current.
Figure 3: Expression of dominant-negative Na+/K+ ATPase decreases AHP amplitude in motor neurons.
Figure 4: Expressing dnATPase in motor neurons decreases the cycle period of network output.
Figure 5: AHP amplitude is proportional to spike number regardless of activity pattern.
Figure 6: AHPs release Shal-type IA channels from inactivation and modify motor neuron intrinsic properties during behaviorally relevant rhythmic depolarization.
Figure 7: AHPs are able to hold intrinsic properties in states approximating those seen during rhythmic activity even in the absence of rhythmic inputs.

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Acknowledgements

We would like to thank E. Marder, B. Trimmer and P. Miller for helpful discussions and critical reading of the manuscript. This work was supported by US National Institutes of Health grant R01 MH067284 to L.C.G.

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S.R.P. and L.C.G. designed the experiments. S.R.P. performed the experiments and analyzed the data. S.R.P. and L.C.G. wrote the paper.

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Correspondence to Leslie C Griffith.

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Pulver, S., Griffith, L. Spike integration and cellular memory in a rhythmic network from Na+/K+ pump current dynamics. Nat Neurosci 13, 53–59 (2010). https://doi.org/10.1038/nn.2444

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