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

Nature. 2010 Jun 24;465(7301):1075-8. doi: 10.1038/nature09087. Epub 2010 Jun 13.

Abstract

Deprivation of afferent inputs in neural circuits leads to diverse plastic changes in both pre- and postsynaptic elements that restore neural activity. The axon initial segment (AIS) is the site at which neural signals arise, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Action Potentials / physiology*
  • Animals
  • Axons / physiology*
  • Birds / physiology
  • Brain Stem / cytology*
  • Cochlea / injuries
  • Cochlea / physiology
  • Hearing Loss / physiopathology
  • Homeostasis
  • Models, Neurological
  • Neuronal Plasticity / physiology*
  • Neurons, Afferent / physiology*
  • Presynaptic Terminals / physiology*
  • Sodium Channels / metabolism*
  • Synaptic Transmission / physiology
  • Time Factors
  • Tympanic Membrane / injuries
  • Vesicular Glutamate Transport Protein 2 / metabolism

Substances

  • Sodium Channels
  • Vesicular Glutamate Transport Protein 2