Support for a synaptic chain model of neuronal sequence generation

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Abstract

In songbirds, the remarkable temporal precision of song is generated by a sparse sequence of bursts in the premotor nucleus HVC. To distinguish between two possible classes of models of neural sequence generation, we carried out intracellular recordings of HVC neurons in singing zebra finches (Taeniopygia guttata). We found that the subthreshold membrane potential is characterized by a large, rapid depolarization 5–10 ms before burst onset, consistent with a synaptically connected chain of neurons in HVC. We found no evidence for the slow membrane potential modulation predicted by models in which burst timing is controlled by subthreshold dynamics. Furthermore, bursts ride on an underlying depolarization of 10-ms duration, probably the result of a regenerative calcium spike within HVC neurons that could facilitate the propagation of activity through a chain network with high temporal precision. Our results provide insight into the fundamental mechanisms by which neural circuits can generate complex sequential behaviours.

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Figure 1: Two broad classes of models for a sequence-generating circuit.
Figure 2: A microdrive for sharp intracellular recording in the singing bird.
Figure 3: Intracellular membrane potential of identified HVC (RA) neurons during singing.
Figure 4: Evidence that calcium channels contribute to burst events in HVC (RA) neurons.
Figure 5: A simple biophysical model to examine the implications of neuronal bursting on the robustness of HVC network propagation.

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Acknowledgements

We thank M. Wilson, S. Seung, A. Andalman, J. Goldberg and A. Gray for comments on earlier versions of this manuscript. We would also like to thank A. Andalman, D. Aronov and T. Ramee for help with acquisition and analysis software. This work is supported by funding from the National Institutes of Health to M.S.F. (MH067105) and M.A.L. (DC009280), and from the Alfred P. Sloan Research Fellowship and the National Science Foundation to D.Z.J. (IOS-0827731).

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M.S.F. and M.A.L. conceived and designed the experiments and analysed the experimental data. M.A.L. acquired the experimental data. M.S.F., M.A.L. and D.Z.J. designed, and D.Z.J. carried out, the modelling experiments. All authors contributed to writing the manuscript.

Corresponding author

Correspondence to Michale S. Fee.

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The authors declare no competing financial interests.

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Long, M., Jin, D. & Fee, M. Support for a synaptic chain model of neuronal sequence generation. Nature 468, 394–399 (2010). https://doi.org/10.1038/nature09514

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