257.19/NN32 - Modulation of gamma oscillations in the pedunculopontine nucleus (PPN)?

DONOFRIO S; KEZUNOVIC N; HYDE J; LUSTER BR; MAHAFFEY S; URBANO FJ; GARCIA-RILL E

Washington, DC

Congreso; 2014 SOCIETY FOR NEUROSCIENCE MEETING, Washington D.C., Nov. 15-19.; 2014

Society for Neuroscience

Reduced gamma band activity has been reported in schizophrenic 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). Our 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. Here, we tested the hypothesis that a) NCS-1 normally regulates gamma band oscillations subserved by these calcium channels, and b) excessive level of NCS-1, such as would be expected with over expression, would decrease gamma band activity. Whole-cell patch-clamp responses were recorded on 9-13 day old adult timed-pregnant Sprague-Dawley rat brainstem slices. Slices were recorded at 370C perfused with oxygenated aCSF in an immersion chamber containing the synaptic blockers gabazine (GABAA antagonist), strychnine (glycine antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (AMPA/kainate receptor antagonist), APV (NMDA receptor antagonist), mecamylamine (nicotinic receptor blocker), and tetrodotoxin (sodium channels blocker). We found, using depolarizing 2 sec current ramps, that after 20-30 min of recording, NCS-1 at 1 uM significantly increased the frequency (percent increase 641%, ANOVA, p