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Axonal site of spike initiation enhances auditory coincidence detection

Abstract

Neurons initiate spikes in the axon initial segment or at the first node in the axon1,2,3,4. However, it is not yet understood how the site of spike initiation affects neuronal activity and function. In nucleus laminaris of birds, neurons behave as coincidence detectors for sound source localization and encode interaural time differences (ITDs) separately at each characteristic frequency (CF)5,6,7. Here we show, in nucleus laminaris of the chick, that the site of spike initiation in the axon is arranged at a distance from the soma, so as to achieve the highest ITD sensitivity at each CF. Na+ channels were not found in the soma of high-CF (2.5–3.3 kHz) and middle-CF (1.0–2.5 kHz) neurons but were clustered within a short segment of the axon separated by 20–50 μm from the soma; in low-CF (0.4–1.0 kHz) neurons they were clustered in a longer stretch of the axon closer to the soma. Thus, neurons initiate spikes at a more remote site as the CF of neurons increases. Consequently, the somatic amplitudes of both orthodromic and antidromic spikes were small in high-CF and middle-CF neurons and were large in low-CF neurons. Computer simulation showed that the geometry of the initiation site was optimized to reduce the threshold of spike generation and to increase the ITD sensitivity at each CF. Especially in high-CF neurons, a distant localization of the spike initiation site improved the ITD sensitivity because of electrical isolation of the initiation site from the soma and dendrites, and because of reduction of Na+-channel inactivation by attenuating the temporal summation of synaptic potentials through the low-pass filtering along the axon.

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Figure 1: The site of action potential generation is remote from the cell soma in high-CF and middle-CF neurons.
Figure 2: Nav channels cluster in the axon at some distance from the soma in high-CF and middle-CF neurons.
Figure 3: Nav channel distribution is optimized for ITD detection.
Figure 4: Cable properties of axon enhance ITD sensitivity during high-frequency inputs.

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Acknowledgements

We thank L. O. Trussell for reading the manuscript, T. Kaneko for advice on preparing antibodies, and M. Dezawa for instruction on immunostaining. This work was supported by a Grant-in-aid from MEXT to H.K. and H.O. Author Contributions H.K. performed all experiments and simulations. T.M.I. contributed to preparing antibodies. H.K. and H.O. wrote the paper together.

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Correspondence to Harunori Ohmori.

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This file contains the Supplementary Methods, Supplementary Tables 1–11, Supplementary Figures 1–9, and additional references.

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Kuba, H., Ishii, T. & Ohmori, H. Axonal site of spike initiation enhances auditory coincidence detection. Nature 444, 1069–1072 (2006). https://doi.org/10.1038/nature05347

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