Intracellular mechanisms modulating gamma band activity in the pedunculopontine nucleus

LUSTER BR; URBANO FJ; GARCIA-RILL E

Chicago, USA

Congreso; 2015 SOCIETY FOR NEUROSCIENCE MEETING, Chicago, Oct. 17-21.; 2015

Society for Neuroscience

The pedunculopontine nucleus (PPN) is a component of the reticular activating system, and is most active during both waking and REM (rapid eye movement) sleep. During waking, our cognitive function is driven by high frequency beta/gamma band activity. However, REM sleep manifests similar high frequency on the cortical EEG. We are interested in determining the differences between gamma activity in waking vs REM sleep. We showed that every cell in the PPN plateaus at beta/gamma band frequencies when depolarized. Moreover, this high frequency activity is mediated by high threshold, voltage-dependent N- and P/Q-type calcium channels. We discovered that the PPN contains cell populations which can manifest gamma band frequencies through only N-type, only P/Q-type, or both N- and P/Q-type calcium channels. Other studies suggest that N-type calcium channels are modulated by the cAMP/PK pathway, which also modulates REM sleep. This study was designed to determine the intracellular mechanisms subserving cells with N-type calcium channels in the PPN. Electrical responses were recorded using whole cell patch clamp electrodes on 11-17 day old sagittal rat brain slices. Intrinsic membrane properties of cells were recorded at 37°C perfused with oxygenated aCSF in an immersion chamber containing the synaptic blockers (SB) gabazine (GABAA antagonist), strychnine (glycine antagonist), CNQX (AMPA/Kainate receptor antagonist), and APV (NMDA receptor antagonist), and also tetrodotoxin (TTX) to block sodium channels. We found that all rat PPN cells (n=13) showed beta/gamma oscillations in the presence of SB+TTX when the membrane potential was depolarized using current ramps. PPN neurons showed beta/gamma oscillations when depolarized above -30 mV, suggesting that their origin may be spatially located beyond voltage-clamp control. In a group of cells tested (n=7), the cAMP/PK inhibitor H-89 along with the P/Q-type calcium channel blocker ω-Agatoxin-IVA combined to inhibit the presence of gamma oscillations (assumed to be N+P/Q cells) (df=13, F=7.04, p0.05). In a final set of cells (n=2), H-89 completely blocked the presence of gamma oscillations while ω-Agatoxin-IVA had no effect on them (assumed to be N-only cells). These results suggest that cells in the PPN that manifest gamma band activity through N-type calcium channels are modulated by the cAMP/PK pathway. We hypothesize that N-only cells are equivalent to ?REM-on? cells in vivo.