Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: Relevance to schizophrenia and bipolar disorder

Stasia D’Onofrio, Nebojsa Kezunovic, James R. Hyde, Brennon Luster, Erick Messias, Francisco J. Urbano, Edgar Garcia-Rill

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Reduced levels of gamma-band activity are present in schizophrenia and bipolar disorder patients. In the same disorders, increased neuronal calcium sensor protein-1 (NCS-1) expression was reported in a series of postmortem studies. These disorders are also characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). The discovery of gamma-band activity in the pedunculopontine nucleus (PPN), the cholinergic arm of the RAS, revealed that such activity was mediated by high-threshold calcium channels that are regulated by NCS-1.We hypothesized that NCS-1 normally regulates gamma-band oscillations through these calcium channels and that excessive levels of NCS-1, such as would be expected with overexpression, decrease gammaband activity. We found that PPN neurons in rat brain slices manifested gamma-band oscillations that were increased by low levels of NCS-1 but suppressed by high levels of NCS-1.Our results suggest that NCS-1 overexpression may be responsible for the decrease in gamma-band activity present in at least some schizophrenia and bipolar disorder patients.

Original languageEnglish
Pages (from-to)709-719
Number of pages11
JournalJournal of Neurophysiology
Volume113
Issue number3
DOIs
StatePublished - 2015
Externally publishedYes

Keywords

  • Arousal
  • Bipolar disorder
  • P/Q-type calcium channels
  • REM sleep
  • Schizophrenia
  • Waking

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