title: Role of the axonal initial segment in psychiatric disorders: function, dysfunction, and intervention.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; Graduate Program in Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; M.D.-Ph.D. Combined Degree Program, The University of Texas Medical Branch at Galveston , Galveston, TX , USA.
authors.forename: Wei-Chun Jim
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; Sealy Center for Molecular Medicine, The University of Texas Medical Branch at Galveston , Galveston, TX , USA.
authors.forename: Carol Lynn
authors.initials: CL
authors.lastname: Nilsson
authors.affiliation: Department of Pharmacology and Toxicology, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; Center for Addiction Research, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; Center for Biomedical Engineering, The University of Texas Medical Branch at Galveston , Galveston, TX , USA ; Mitchell Center for Neurodegenerative Diseases, The University of Texas Medical Branch at Galveston , Galveston, TX , USA.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Laezza
keywords: RDoC; axonal initial segment; neuronal excitability; neuroplasticity; psychiatric disorder; signaling pathways