D'Onofrio Stasia, Kezunovic Nebojsa, Hyde James R, Luster Brennon, Messias Erick, Urbano Francisco J, Garcia-Rill Edgar
Center for Translational Neuroscience, Departments of Neurobiology and Developmental Sciences and Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas; and.
Instituto de Fisiología, Biología Molecular y Neurociencias, Consejo Nacional de Investigaciones Científicas y Técnicas, University of Buenos Aires, Buenos Aires, Argentina.
J Neurophysiol. 2015 Feb 1;113(3):709-19. doi: 10.1152/jn.00828.2014. Epub 2014 Nov 5.
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.
精神分裂症和双相情感障碍患者的γ波段活动水平降低。在一系列尸检研究中报告了这些疾病中神经元钙传感器蛋白-1（NCS-1）表达增加。这些疾病还具有睡眠失调的特征，提示网状激活系统（RAS）发挥了作用。在RAS的胆碱能分支脚桥核（PPN）中发现γ波段活动，揭示了这种活动是由受NCS-1调节的高阈值钙通道介导的。我们假设NCS-1通常通过这些钙通道调节γ波段振荡，并且NCS-1的过量水平（如过表达时预期的那样）会降低γ波段活动。我们发现大鼠脑片中的PPN神经元表现出γ波段振荡，低水平的NCS-1会增强这种振荡，而高水平的NCS-1则会抑制它。我们的结果表明，NCS-1过表达可能是至少部分精神分裂症和双相情感障碍患者γ波段活动降低的原因。
