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

J Neurophysiol. 2015 Feb 1;113(3):709-19. doi: 10.1152/jn.00828.2014. Epub 2014 Nov 5.

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 gamma-band 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.

Keywords: P/Q-type calcium channels; REM sleep; arousal; bipolar disorder; schizophrenia; waking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bipolar Disorder / metabolism
  • Calcium Channels / metabolism
  • Gamma Rhythm*
  • Neuronal Calcium-Sensor Proteins / genetics
  • Neuronal Calcium-Sensor Proteins / metabolism*
  • Neurons / metabolism
  • Neurons / physiology
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Pedunculopontine Tegmental Nucleus / cytology
  • Pedunculopontine Tegmental Nucleus / metabolism
  • Pedunculopontine Tegmental Nucleus / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Schizophrenia / metabolism

Substances

  • Calcium Channels
  • Neuronal Calcium-Sensor Proteins
  • Neuropeptides
  • frequenin calcium sensor proteins