Implications of cellular models of dopamine neurons for schizophrenia

Na Yu, Kristal R. Tucker, Edwin S. Levitan, Paul D. Shepard, Carmen C. Canavier

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Scopus citations

Abstract

Midbrain dopamine neurons are pacemakers in vitro, but in vivo they fire less regularly and occasionally in bursts that can lead to a temporary cessation in firing produced by depolarization block. The therapeutic efficacy of antipsychotic drugs used to treat the positive symptoms of schizophrenia has been attributed to their ability to induce depolarization block within a subpopulation of dopamine neurons. We summarize the results of experiments characterizing the physiological mechanisms underlying the ability of these neurons to enter depolarization block in vitro, and our computational simulations of those experiments. We suggest that the inactivation of voltage-dependent Na+ channels, and, in particular, the slower component of this inactivation, is critical in controlling entry into depolarization block. In addition, an ether-a-go-related gene (ERG) K + current also appears to be involved by delaying entry into and speeding recovery from depolarization block. Since many antipsychotic drugs share the ability to block this current, ERG channels may contribute to the therapeutic effects of these drugs.

Original languageEnglish (US)
Title of host publicationComputational Neuroscience
PublisherElsevier
Pages53-82
Number of pages30
ISBN (Print)9780123978974
DOIs
StatePublished - Jan 1 2014

Publication series

NameProgress in Molecular Biology and Translational Science
Volume123
ISSN (Print)1877-1173

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

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    Yu, N., Tucker, K. R., Levitan, E. S., Shepard, P. D., & Canavier, C. C. (2014). Implications of cellular models of dopamine neurons for schizophrenia. In Computational Neuroscience (pp. 53-82). (Progress in Molecular Biology and Translational Science; Vol. 123). Elsevier. https://doi.org/10.1016/B978-0-12-397897-400011-5