University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Medicine and Radiology
  • Medicine and Radiology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Ca(V)3.2 drives sustained burst-firing, which is critical for absence seizure propagation in reticular thalamic neurons

    Thumbnail
    Download
    Published version (1.867Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    12
    12
    Author
    Cain, SM; Tyson, JR; Choi, H-B; Ko, R; Lin, PJC; LeDue, JM; Powell, KL; Bernier, L-P; Rungta, RL; Yang, Y; ...
    Date
    2018-04-01
    Source Title
    Epilepsia
    Publisher
    WILEY
    University of Melbourne Author/s
    O'Brien, Terence; Powell, Kim
    Affiliation
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Cain, S. M., Tyson, J. R., Choi, H. -B., Ko, R., Lin, P. J. C., LeDue, J. M., Powell, K. L., Bernier, L. -P., Rungta, R. L., Yang, Y., Cullis, P. R., O'Brien, T. J., MacVicar, B. A. & Snutch, T. P. (2018). Ca(V)3.2 drives sustained burst-firing, which is critical for absence seizure propagation in reticular thalamic neurons. EPILEPSIA, 59 (4), pp.778-791. https://doi.org/10.1111/epi.14018.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255836
    DOI
    10.1111/epi.14018
    Abstract
    OBJECTIVE: Genetic alterations have been identified in the CACNA1H gene, encoding the CaV 3.2 T-type calcium channel in patients with absence epilepsy, yet the precise mechanisms relating to seizure propagation and spike-wave-discharge (SWD) pacemaking remain unknown. Neurons of the thalamic reticular nucleus (TRN) express high levels of CaV 3.2 calcium channels, and we investigated whether a gain-of-function mutation in the Cacna1h gene in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) contributes to seizure propagation and pacemaking in the TRN. METHODS: Pathophysiological contributions of CaV 3.2 calcium channels to burst firing and absence seizures were assessed in vitro using acute brain slice electrophysiology and quantitative real-time polymerase chain reaction (PCR) and in vivo using free-moving electrocorticography recordings. RESULTS: TRN neurons from GAERS display sustained oscillatory burst-firing that is both age- and frequency-dependent, occurring only in the frequencies overlapping with GAERS SWDs and correlating with the expression of a CaV 3.2 mutation-sensitive splice variant. In vivo knock-down of CaV 3.2 using direct thalamic injection of lipid nanoparticles containing CaV 3.2 dicer small interfering (Dsi) RNA normalized TRN burst-firing, and in free-moving GAERS significantly shortened seizures. SIGNIFICANCE: This supports a role for TRN CaV 3.2 T-type channels in propagating thalamocortical network seizures and setting the pacemaking frequency of SWDs.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45770]
    • Medicine and Radiology - Research Publications [2347]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors