478.06/JJJ20. Effect of Modafinil on P/Q-type calcium channel-dependent oscillations in the PPN.

DONOFRIO SM; KEZUNOVIC N; URBANO FJ; GARCIA-RILL E

San Diego, CA, USA.

Congreso; 2013 Society for Neuroscience Meeting.; 2013

Society for Neuroscience

The pedunculopontine nucleus (PPN) is a component of the reticular activating system, and is involved in the activated states of waking and paradoxical sleep. Gamma oscillations (~20-80 Hz) are evident in all PPN neurons and are mediated by high threshold voltage-dependent N- and P/Q-type calcium channels. We tested the hypothesis that the stimulant Modafinil (MOD) would modulate either the amplitude or the frequency of ramp-induced gamma band oscillations in PPN neurons activated by the nonspecific cholinergic agonist Carbachol (CAR). Whole-cell patch-clamp responses were recorded on 9-13 day old 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), and mecamylamine (nicotinic receptor blocker), and also Tetrodotoxin to block sodium channels. CAR and MOD were used to study changes in P/Q-type calcium channel-dependent oscillatory behavior of PPN neurons. Intrinsic membrane properties were measured using 1 sec long current ramp protocols. We found that persistent application of MOD, when applied alone, did not change the frequency or the amplitude of ramp-induced oscillations (n=13; p=0.31). However, when CAR was added to the extracellular solution together with MOD, both the frequency (n=10; p=0.01) and the amplitude (n=14; p