Modulation of gamma oscillations in the pedunculopontine nucleus by neuronal calcium sensor protein-1: relevance to schizophrenia and bipolar disorder.
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.
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
Stasia
S
D'Onofrio
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
Nebojsa
N
Kezunovic
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
James R
JR
Hyde
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
Brennon
B
Luster
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
Erick
E
Messias
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, University of Buenos Aires, Buenos Aires, Argentina.
Francisco J
FJ
Urbano
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and GarciaRillEdgar@uams.edu.
Edgar
E
Garcia-Rill
D000818:Animals; D001714:Bipolar Disorder / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D065818:Gamma Rhythm; D051580:Neuronal Calcium-Sensor Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000378:metabolism
D015220:Calcium Channels; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins
P/Q-type calcium channels; REM sleep; arousal; bipolar disorder; schizophrenia; waking