IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Novel treatment for schizophrenia
Autor/es:
DONOFRIO S; KEZUNOVIC N; HYDE J; LUSTER BR; URBANO FJ; MESSIAS E; GARCIA-RILL E
Lugar:
Little Rock, Arkansas, USA.
Reunión:
Congreso; SE Regional IDeA Meeting 2013.; 2013
Institución organizadora:
University of Arkansas for Medical Sciences
Resumen:
Neuronal calcium sensor protein (NCS-1) has been found to be overexpressed in the brains of schizophrenic and bipolar patients but not depressed patients or controls. We discovered that almost all cells in the reticular activating system (RAS), especially the pedunculopontine nucleus (PPN), fire maximally at gamma band frequencies and that such activity is subserved by subthreshold membrane oscillations due to high threshold, voltage-dependent N- and P/Q-type calcium channels. Using patch clamp recordings in 9-13 day rat brainstem slices, we found that NCS-1 (in the recording pipette) at low levels (1 uM) increased the frequency and amplitude of membrane oscillations induced by current ramps or by the nonspecific cholinergic agonist carbachol (CAR). In contrast, high levels (10 uM) of NCS-1 were found to block gamma band oscillations in PPN neurons, but exposure to the stimulant modafinil (MOD, 300 mM) were found to restore oscillations in the presence of high levels of NCS-1. These findings suggest that, a) NCS-1 at low levels potentiates gamma band activity in the PPN, b) NCS-1 at high levels blocks gamma band oscillations in the PPN, c) NCS-1 overexpression may be responsible for the decrease in gamma band activity in schizophrenia, and d) MOD restored gamma band activity under high levels of NCS-1, suggesting a novel treatment for schizophrenia. Supported by NIH awards R01 NS020246 and P20 GM103425 (EGR), and by ANPCyT-FONCyT-BID 1728 OC.AR. PICT 2007-1009, PICT 2008-2019 and PIDRI-PRH 2007 (FJU).