The site of action potential initiation in cerebellar Purkinje neurons

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Abstract

Knowledge of the site of action potential initiation is essential for understanding how synaptic input is converted into neuronal output. Previous studies have shown that the lowest-threshold site for initiation of action potentials is in the axon. Here we use recordings from visualized rat cerebellar Purkinje cell axons to localize the site of initiation to a well-defined anatomical structure: the first node of Ranvier, which normally forms at the first axonal branch point.

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Figure 1: Direct measurement of the initiation site during spontaneous action potential firing.
Figure 2: The action potential initiation site corresponds to the first branch point.
Figure 3: A model of action potential initiation in Purkinje neurons.

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Acknowledgements

We thank J. T. Davie, J.J.B. Jack, C. Racca and A. Roth for helpful comments; V. Bennett for the ankyrin-G antibody; and A. Gidon, L. Ramakrishnan, E. Rancz, and A. Roth for help with reconstructions and videos. This work was supported by grants from the Wellcome Trust, European Commission, and the Gatsby Foundation. M.L. is a Long-Term Fellow of the Human Frontier Science Program, and T.B. was funded by the Wellcome Trust 4-year PhD Programme in Neuroscience.

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Correspondence to Michael Häusser.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Methods (PDF 55 kb)

Supplementary Video 1

Initiation of action potentials in the Purkinje cell model. Movie showing spatial spread of the action potential during spontaneous firing in the Purkinje cell model. The main panel shows the morphology of the reconstructed Purkinje cell, with voltage in each section coded by color. The membrane potential and capacitive current at the first node and at the soma are shown as insets. (MOV 22935 kb)

Supplementary Video 2

Spatial profile of the action potential along the axon. Results from a simulation in the Purkinje cell model (same as in Supplementary Video 1), plotting action potential amplitude in the main axon against distance from the soma, showing the temporal evolution of the spatial spread of voltage during action potential initiation. The model was designed such that the source of the ramp current underlying spontaneous firing originates from the soma (consistent with experimental data showing spontaneous firing in isolated Purkinje cell somata), and the axon is hyperpolarized by its lower resting potential. Nevertheless, the first node 'takes off' first, supplying the current which in turn activates the initial segment, soma, second node, and the rest of the axon; only after initiation at the first node does the action potential spread to encompass multiple nodes as it propagates down the axon. (MOV 9004 kb)

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Clark, B., Monsivais, P., Branco, T. et al. The site of action potential initiation in cerebellar Purkinje neurons. Nat Neurosci 8, 137–139 (2005) doi:10.1038/nn1390

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