Open AccessInteraction between neuronal calcium sensor protein 1 and lithium in pedunculopontine neurons
Author(s) -
D'Onofrio Stasia,
Hyde James,
GarciaRill Edgar
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13246
Subject(s) - pedunculopontine nucleus , lithium (medication) , bipolar disorder , endocrinology , reticular activating system , chemistry , medicine , neuroscience , oscillation (cell signaling) , reticular connective tissue , midbrain reticular formation , biophysics , reticular formation , psychology , biology , biochemistry , central nervous system , anatomy , disease , parkinson's disease , deep brain stimulation
Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system ( RAS ). Postmortem studies showed increased expression of neuronal calcium sensor protein 1 ( NCS ‐1) in the brains of some bipolar disorder patients, and reduced or aberrant gamma band activity is present in the same disorder. Lithium (Li + ) has been shown to effectively treat the mood disturbances in bipolar disorder patients. We previously showed that NCS ‐1 at low levels increased, and at high levels decreased, gamma oscillations in RAS pedunculopontine neurons ( PPN ), and that Li + decreased these oscillations. We previously described the effects of each agent on oscillations, G‐protein mechanisms, and Ca 2+ currents. However, we designed the present experiments to determine the nature of the interaction of NCS ‐1 and Li + at physiological concentrations that would have an effect within minutes of application. As expected, Li + decreased gamma oscillation amplitude, while NCS ‐1 increased the amplitude of gamma oscillations. We identified NCS ‐1 at 2 μmol/L as a concentration that increased gamma oscillations within 5–10 min, and Li + at 10 μmol/L as a concentration that decreased gamma oscillations within 5 min. The combined application of NCS ‐1 and Li + at these concentrations showed that Li + reduced the effects of NCS ‐1 on oscillation amplitude within 5–10 min. These results demonstrate that at physiological levels, Li + acts to reduce the effects of NCS ‐1 so that, given over expression of NCS ‐1, Li + would have salutary effects.