title: Lithium decreases the effects of neuronal calcium sensor protein 1 in pedunculopontine neurons.
abstract: Human postmortem studies reported 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. Bipolar disorder is characterized by sleep dysregulation, suggesting a role for the reticular activating system (RAS). Lithium (Li(+)) has been shown to effectively treat the mood disturbances in bipolar disorder patients and was proposed to act by inhibiting the interaction betweenNCS-1 and inositol 1,4,5-triphosphate receptor protein (InsP3R).NCS-1 is known to enhance the activity of InsP3R, and of Ca(2+)-mediated gamma oscillatory activity in the pedunculopontine nucleus (PPN), part of theRAS This study aimed to determine the nature of some of the intracellular mechanisms of Li(+)on ratPPNcells and to identify the interaction between Li(+)andNCS-1. Since Li(+)has been shown to act by inhibiting the enhancing effects ofNCS-1, we tested the hypothesis that Li(+)would reduced the effects of overexpression ofNCS-1 and prevent the downregulation of gamma band activity. Li(+)decreased gamma oscillation frequency and amplitude by downregulating Ca(2+)channel activity, whereasNCS-1 reduced the effect of Li(+)on Ca(2+)currents. These effects were mediated by a G-protein overinhibition of Ca(2+)currents. These results suggest that Li(+)affected intracellular pathways involving the activation of voltage-gated Ca(2+)channels mediated by an intracellular mechanism involving voltage-dependent activation of G proteins, thereby normalizing gamma band oscillations mediated by P/Q-type calcium channels modulated byNCS-1.
authors.affiliation: Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Stasia
authors.initials: S
authors.lastname: D'Onofrio
authors.affiliation: IFIBYNE-CONICET-UBA, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Urbano
authors.affiliation: Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas Department of Psychiatry, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Erick
authors.initials: E
authors.lastname: Messias
authors.affiliation: Center for Translational Neuroscience, Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas GarciaRillEdgar@uams.edu.
authors.forename: Edgar
authors.initials: E
authors.lastname: Garcia-Rill
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D065818:Gamma Rhythm / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007700:Kinetics; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D051580:Neuronal Calcium-Sensor Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009479:Neuropeptides / Q000494:pharmacology*; D045042:Pedunculopontine Tegmental Nucleus / Q000187:drug effects* / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D020864:Calcium Channels, N-Type; D018020:Lithium Compounds; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D011994:Recombinant Proteins; C101464:frequenin calcium sensor proteins
keywords: Bipolar disorder; Gamma band activity; sleep/wake