Mechanism behind gamma band activity in the pedunculopontine nucleus

Abstract

The pedunculopontine nucleus (PPN), part of the reticular activating system, modulates waking and paradoxical sleep. During waking and paradoxical sleep, EEG responses are characterized by low-amplitude, high-frequency oscillatory activity in the beta–gamma band range (20–80 Hz). We have previously reported that gamma band activity may be intrinsically generated by the membrane electroresponsiveness of PPN neurons, and that the neuronal ensemble generates different patterns of gamma activity in response to specific transmitters. This study attempted to identify the voltage-gated calcium and potassium channels involved in the rising and falling phases of gamma oscillations in PPN neurons. We found that all rat (8–14 day) PPN cell types showed gamma oscillations in the presence of TTX and synaptic blockers when membrane potential was depolarized using current ramps. PPN neurons showed gamma oscillations when voltage-clamped at holding potentials above )30 mV, suggesting that their origin may be spatially located beyond voltage-clamp control. The average frequency for all PPN cell types was 23 ± 1 Hz and this increased under carbachol (47 ± 2 Hz; anova df = 64, t = 12.5, P < 0.001). The N-type calcium channel blocker x-conotoxin-GVIA partially reduced gamma oscillations, while the P ⁄ Q-type blocker x-agatoxin-IVA abolished them. Both x-CgTX and x-Aga blocked voltage-dependent calcium currents, by 56 and 52% respectively. The delayed rectifier-like potassium channel blocker a-dendrotoxin also abolished gamma oscillations. In carbachol-induced PPN population responses, x-agatoxin-IVA reduced higher, and x-CgTx mostly lower, frequencies. These results suggest that voltage-dependent P ⁄ Q- and, to a lesser extent, N-type calcium channels mediate gamma oscillations in PPN.