Role of the axonal initial segment in psychiatric disorders: Function, dysfunction, and intervention

Wei Chun Jim Hsu, Carol Lynn Nilsson, Fernanda Laezza

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


The progress of developing effective interventions against psychiatric disorders has been limited due to a lack of understanding of the underlying cellular and functional mechanisms. Recent research findings focused on exploring novel causes of psychiatric disorders have highlighted the importance of the axonal initial segment (AIS), a highly specialized neuronal structure critical for spike initiation of the action potential. In particular, the role of voltage-gated sodium channels, and their interactions with other protein partners in a tightly regulated macromolecular complex has been emphasized as a key component in the regulation of neuronal excitability. Deficits and excesses of excitability have been linked to the pathogenesis of brain disorders. Identification of the factors and regulatory pathways involved in proper AIS function, or its disruption, can lead to the development of novel interventions that target these mechanistic interactions, increasing treatment efficacy while reducing deleterious off-target effects for psychiatric disorders.

Original languageEnglish (US)
Article numberArticle 109
JournalFrontiers in Psychiatry
Issue numberAUG
StatePublished - 2014


  • Axonal initial segment
  • Neuronal excitability
  • Neuroplasticity
  • Psychiatric disorder
  • RDoC
  • Signaling pathways

ASJC Scopus subject areas

  • Psychiatry and Mental health


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