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.
At a glance
- Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004) &
- Relative contributions of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons. J. Neurosci. 26, 1935–1944 (2006) &
- Site of action potential initiation in layer 5 pyramidal neurons. J. Neurosci. 26, 1854–1863 (2006) &
- Synaptic activity and the construction of cortical circuits. Science 274, 1133–1138 (1996) &
- Strength through diversity. Neuron 60, 477–482 (2008) &
- Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nature Neurosci. 2, 515–520 (1999) , &
- Activity-dependent long term potentiation of intrinsic excitability in hippocampal CA1 pyramidal neurons. J. Neurosci. 25, 1750–1760 (2005) , , , &
- Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits. Science 311, 233–235 (2006) et al.
- Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron 55, 633–647 (2007) , &
- Selective control of cortical axonal spikes by a slowly inactivating K+ current. Proc. Natl Acad. Sci. USA 104, 11453–11458 (2007) , , &
- Axon initial segment Ca2+ channels influence action potential generation and timing. Neuron 61, 259–271 (2009) &
- Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation. Nature Neurosci. 12, 996–1002 (2009) et al.
- Axonal site of spike initiation enhances auditory coincidence detection. Nature 444, 1069–1072 (2006) , &
- Roles of axonal sodium channels in precise auditory time coding at nucleus magnocellularis of the chick. J. Physiol. (Lond.) 587, 87–100 (2009) &
- Afferent influences on brain stem auditory nuclei of the chicken: neuron number and size following cochlea removal. J. Comp. Neurol. 231, 435–445 (1985) &
- Auditory system development: primary auditory neurons and their targets. Annu. Rev. Neurosci. 25, 51–101 (2002) &
- Cochlear damage changes the distribution of vesicular glutamate transporters associated with auditory and nonauditory inputs to the cochlear nucleus. J. Neurosci. 29, 4210–4217 (2009) , , , &
- The functional organization and assembly of the axon initial segment. Curr. Opin. Neurobiol. 18, 307–313 (2008) &
- Afferent influences on brain stem auditory nuclei of the chicken: effects of conductive and sensorineural hearing loss on n. magnocellularis. J. Comp. Neurol. 238, 371–381 (1985) &
- Critical periods during sensory development. Curr. Opin. Neurobiol. 10, 138–145 (2000) , &
- Development of the auditory brainstem of birds: comparison between barn owls and chickens. Hear. Res. 147, 1–20 (1998) &
- Neuronal architecture in nucleus magnocellularis of the chicken auditory system with observations on nucleus laminaris: a light and electron microscope study. Neuroscience 7, 809–836 (1982) &
- Activity-dependent regulation of the potassium channel subunits Kv1.1 and Kv3.1. J. Comp. Neurol. 470, 93–106 (2004) , , &
- Evidence that climbing fibers control an intrinsic spike generator in cerebellar Purkinje cells. J. Neurosci. 24, 4510–4517 (2004) &
- Afferent influences on brainstem auditory nuclei of the chick: nucleus magnocellularis neuronal activity following cochlea removal. Brain Res. 557, 37–47 (1991) , &
- A single vesicular glutamate transporter is sufficient to fill a synaptic vesicle. Neuron 49, 11–16 (2006) et al.
- Development of spontaneous miniature EPSCs in mouse AVCN neurons during a critical period of afferent-dependent neuron survival. J. Neurophysiol. 97, 635–646 (2007) , &
- Electrical activity and cytosolic calcium regulate levels of tetrodotoxin-sensitive sodium channels in cultured rat muscle cells. Proc. Natl Acad. Sci. USA 81, 262–266 (1984) &
- Organization and development of brain stem auditory nuclei of the chicken: tonotopic organization of N. magnocellularis and N. laminaris. J. Comp. Neurol. 164, 411–433 (1975) &
- Interaction of the Nav1.2a subunit of the voltage-dependent sodium channel with nodal ankyrinG. In vitro mapping of the interacting domains and association in synaptosomes. J. Biol. Chem. 277, 28996–29004 (2002) et al.
- Supplementary Information (4.1M)
This file contains Supplementary Figures 1-8 with legends and References.