Interaction between neuronal calcium sensor protein 1 and lithium in pedunculopontine neurons.

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 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.