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Presynaptic activity regulates Na+ channel distribution at the axon initial segment

Abstract

Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity1. The axon initial segment (AIS) is the site at which neural signals arise2,3, and should be the most efficient site to regulate neural activity. However, none of the plasticity currently known involves the AIS. We report here that deprivation of auditory input in an avian brainstem auditory neuron leads to an increase in AIS length, thus augmenting the excitability of the neuron. The length of the AIS, defined by the distribution of voltage-gated Na+ channels and the AIS anchoring protein, increased by 1.7 times in seven days after auditory input deprivation. This was accompanied by an increase in the whole-cell Na+ current, membrane excitability and spontaneous firing. Our work demonstrates homeostatic regulation of the AIS, which may contribute to the maintenance of the auditory pathway after hearing loss. Furthermore, plasticity at the spike initiation site suggests a powerful pathway for refining neuronal computation in the face of strong sensory deprivation.

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Figure 1: Auditory deprivation increased the length of the AIS.
Figure 2: Elongation of the AIS is activity dependent and develops within several days.
Figure 3: Auditory deprivation increased axonal I Na and excitability of neurons.
Figure 4: Auditory deprivation has little effect on synaptic transmission.

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Acknowledgements

We thank G. Alcaraz for providing ankyrin-G antibody. We also thank L. O. Trussell for advice and for editing the manuscript; M. N. Rasband, T. M. Ishii and R. Yamada for reading the manuscript; and K. Bender for discussions. This work was supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan, to H.K. and H.O.

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H.K. designed and carried out all experiments and wrote the paper. Y.O. carried out preliminary experiments. H.O. helped with acoustic stimulation.

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Correspondence to Hiroshi Kuba.

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The authors declare no competing financial interests.

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Kuba, H., Oichi, Y. & Ohmori, H. Presynaptic activity regulates Na+ channel distribution at the axon initial segment. Nature 465, 1075–1078 (2010). https://doi.org/10.1038/nature09087

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