Producción CyT
2013 Society for Neuroscience Meeting Abstracts - 478.04/JJJ18. Muscarinic modulation of gamma band activity in the pedunculopontine nucleus (PPN).
Congreso
Autoría:
Kezunovic N ; Hyde JR ; Goitia B ; Bisagno V ; Urbano FJ ; Garcia-Rill EFecha:
2013Editorial y Lugar de Edición:
Society for Neuroscience, 1121 14th Street, NW, Suite 1010Resumen *
The pedunculopontine nucleus (PPN) is part of the reticular activating system, and receives cholinergic input from the contralateral PPN and laterodorsal tegmental nuclei. We reported that persistent application of the nonspecific cholinergic agonist carbachol (CAR) increased the frequency of oscillatory activity in PPN neurons, which we identified as dependent on voltage-gated, high threshold P/Q-type calcium channels. Here, we tested the hypothesis that M2 muscarinic receptors and G-proteins associated with M2 receptors mediate the increase in CAR-induced oscillatory frequency in PPN cells. Whole-cell patch-clamp responses were recorded on 9-13 day old rat brainstem slices at 37oC 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. Using 30 sec depolarizing ramps, PPN neurons (n=185) began oscillating around -40 mV and reached their peak around -20 mV membrane potential. Acute (short duration) application of CAR blocked the oscillatory activity through M2 muscarinic receptors (blocked by the M2 antagonist pirenzepine, but not the M1 antagonist methoctramine), an effect reversed with atropine. However, persistent (long duration) application of CAR significantly increased the frequency of ramp-induced oscillatory activity in PPN neurons through M2 receptors [40±1Hz (CAR) vs 23±1Hz (without CAR); p<0.001]. We then tested the effects of the G-protein antagonist guanosine 5 -[beta-thio] diphosphate trilithium salt (GDP-beta-S), and the G-protein agonist 5-[gamma-thio] triphosphate trilithium salt (GTP-gamma-S). We found, using a three-step protocol in voltage clamp mode, that the increase in the frequency of oscillations induced by M2 cholinergic receptors was dependent on a voltage-independent G-protein mechanism. These results suggest that short-lasting cholinergic input to the PPN results in inhibition of high frequency activity. However, long duration or persistent cholinergic input is mediated by G-proteins that otherwise would inactivate high threshold, voltage-dependent calcium channels. That is, tonic cholinergic inhibition creates a permissive mechanism that allows P/Q-type calcium channel-mediated oscillations to occur. Therefore, continuous sensory input onto PPN dendrites would induce high frequency activity mainly through P/Q-type calcium channels, but only during continuous, not acute, cholinergic input. GRANTS: NIH award NS020246; NIH award RR020146; ANPCyT-FONCyT-BID 1728 OC.AR. PICT 2007-1009; ANPCyT-FONCyT-BID 1728 OC.AR. PICT 2008-2019. Información suministrada por el agente en SIGEVAPalabras Clave
MUSCARINIC RECEPTORSAROUSALG-PROTEINSCALCIUM CHANNELSGAMMA OSCILLATIONS