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.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Stuart, G., Spruston, N., Sakmann, B. & Hausser, M. Action potential initiation and backpropagation in neurons of the mammalian CNS. Trends Neurosci. 20, 125–131 (1997)
Clark, B. A., Monsivais, P., Branco, T., London, M. & Hausser, M. The site of action potential initiation in cerebellar Purkinje neurons. Nature Neurosci. 8, 137–139 (2005)
Palmer, L. M. & Stuart, G. J. Site of action potential initiation in layer 5 pyramidal neurons. J. Neurosci. 26, 1854–1863 (2006)
Khaliq, Z. M. & Raman, I. M. Relative contribution of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons. J. Neurosci. 26, 1935–1944 (2006)
Knudsen, E. I. & Konishi, M. Mechanisms of sound localization in the barn owl (Tyto alba). J. Comp. Physiol. [A] 133, 13–21 (1979)
Moiseff, A. & Konishi, M. Neuronal and behavioral sensitivity to binaural time differences in the owl. J. Neurosci. 1, 40–48 (1981)
Carr, C. E. & Konishi, M. A circuit for detection of interaural time differences in the brain stem of the barn owl. J. Neurosci. 10, 3227–3246 (1990)
Reyes, A. D., Rubel, E. W. & Spain, W. J. In vitro analysis of optimal stimuli for phase-locking and time-delayed modulation of firing in avian nucleus laminaris neurons. J. Neurosci. 16, 993–1007 (1996)
Kuba, H., Yamada, R. & Ohmori, H. Evaluation of the limiting acuity of coincidence detection in nucleus laminaris of the chicken. J. Physiol. (Lond.) 552, 611–620 (2003)
Pena, J. L., Viete, S., Albeck, Y. & Konishi, M. Tolerance to sound intensity of binaural coincidence detection in the nucleus laminaris of the owl. J. Neurosci. 16, 7046–7054 (1996)
Funabiki, K., Koyano, K. & Ohmori, H. The role of GABAergic inputs for coincidence detection in the neurones of nucleus laminaris of the chick. J. Physiol. (Lond.) 508, 851–869 (1998)
Agmon-Snir, H., Carr, C. E. & Rinzel, J. The role of dendrites in auditory coincidence detection. Nature 393, 268–272 (1998)
Kuba, H., Koyano, K. & Ohmori, H. Synaptic depression improves coincidence detection in the nucleus laminaris in brainstem slices of the chick embryo. Eur. J. Neurosci. 15, 984–990 (2002)
Cook, D. L., Schwindt, P. C., Grande, L. A. & Spain, W. J. Synaptic depression in the localization of sound. Nature 421, 66–70 (2003)
Rubel, E. W. & Parks, T. N. Organization and development of the brain stem auditory nuclei of the chicken: tonotopic organization of N. magnocellularis and N. laminaris. J. Comp. Neurol. 164, 411–434 (1975)
Smith, D. J. & Rubel, E. W. Organization and development of brain stem auditory nuclei of the chicken: dendritic gradients in nucleus laminaris. J. Comp. Neurol. 186, 213–240 (1979)
Kuba, H., Yamada, R., Fukui, I. & Ohmori, H. Tonotopic specialization of auditory coincidence detection in nucleus laminaris of the chick. J. Neurosci. 25, 1924–1934 (2005)
Carr, C. E. & Boudreau, R. E. An axon with a myelinated initial segment in the bird auditory system. Brain Res. 628, 330–334 (1993)
Caldwell, J. H., Schaller, K. L., Lasher, R. S., Peles, E. & Levinson, S. R. Sodium channel Nav1.6 is localized at nodes of Ranvier, dendrites, and synapses. Proc. Natl Acad. Sci. USA 97, 5616–5620 (2000)
Rasband, M. N. & Shrager, P. Ion channel sequestration in central nervous system axon. J. Physiol. (Lond.) 525, 63–73 (2000)
Scott, L. L., Mathews, P. J. & Golding, N. L. Posthearing developmental refinement of temporal processing in principal neurons of the medial superior olive. J. Neurosci. 25, 7887–7895 (2005)
Colbert, C. M. & Johnston, D. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons. J. Neurosci. 16, 6676–6686 (1996)
Kuba, H., Koyano, K. & Ohmori, H. Development of membrane conductance improves coincidence detection in the nucleus laminaris of the chicken. J. Physiol. (Lond.) 540, 529–542 (2002)
Yamada, R., Kuba, H., Ishii, T. M. & Ohmori, H. Hyperpolarization-activated cyclic nucleotide-gated cation channels regulate auditory coincidence detection in nucleus laminaris of the chick. J. Neurosci. 25, 8867–8877 (2005)
Rathouz, M. & Trussell, L. Characterization of outward currents in neurons of the avian nucleus magnocellularis. J. Neurophysiol. 80, 2824–2835 (1998)
Simon, J. Z., Carr, C. E. & Shamma, S. A. A dendritic model of coincidence detection in the avian brainstem. Neurocomputing 26–27, 263–269 (1999)
Rothman, J. S. & Manis, P. B. The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3097–3113 (2003)
Hines, M. L., Morse, T., Migliore, M., Carnevale, N. T. & Shepherd, G. M. Model DB: a database to support computational neuroscience. J. Comput. Neurosci. 17, 7–11 (2004)
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.
Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.
About this article
Cite this article
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
Chronic α1-Na/K-ATPase inhibition reverses the elongation of the axon initial segment of the hippocampal CA1 pyramidal neurons in Angelman syndrome model mice
Nature Communications (2021)
Intramuscular Botulinum toxin A injections induce central changes to axon initial segments and cholinergic boutons on spinal motoneurones in rats
Scientific Reports (2020)
Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons
Scientific Reports (2017)
Nature Neuroscience (2016)