High-threshold Ca²⁺channels behind gamma band activity in the pedunculopontine nucleus (PPN)

Abstract

The pedunculopontine nucleus (PPN) is part of the Reticular Activating System, and active during waking and REM sleep. Previous results showed that all PPN cells plateau at gamma frequencies and intrinsic membrane oscillations in PPN neurons are mediated by high-threshold N- and P/Q-type Ca2+ channels. The present study was designed to determine whether some PPN cells have only N-, only P/Q-, or both N- and P/Q-type Ca2+ channels. We used patch-clamp recordings in PPN cells in slices from anesthetized rat pups in the presence of synaptic receptor blockers (SB) and Tetrodotoxin (TTX), and applied ramps to induce intrinsic membrane oscillations. We found that all PPN cell types showed gamma oscillations in the presence of SB+TTX when using current ramps. In 50% of cells, the N-type Ca2+ channel blocker ω-Conotoxin-GVIA (ω-CgTx) reduced gamma oscillation amplitude, while subsequent addition of the P/Q-type blocker ω-Agatoxin-IVA (ω-Aga) blocked the remaining oscillations. Another 20% manifested gamma oscillations that were not significantly affected by the addition of ω-CgTx, however, ω-Aga blocked the remaining oscillations. In 30% of cells, ω-Aga had no effect on gamma oscillations, while ω-CgTx blocked them. These novel results confirm the segregation of populations of PPN cells as a function of the calcium channels expressed, that is, the presence of cells in the PPN that manifest gamma band oscillations through only N-type, only P/Q-type, and both N-type and P/Q-type Ca2+ channels.

Role of Calcium Channels in Bipolar Disorder

“…Similar results were found during recordings of voltage-dependent calcium currents. These results confirm the presence of cells in the PPN that manifest gamma band oscillations through only N-type (30%), only P/Q-type (20%), and both N- and P/Q-type (50%) calcium channels [121,122]. …”

“…This new cell type classification proposes that some PPN neurons fire only during REM sleep (“REM-on”, N-type only), only during waking (“Wake-on”, P/Q-type only), or during both waking and REM sleep (“Wake/REM-on”, N-type + P/Q-type) [121,122]. Armed with this information, we could now address the role of NCS-1 and lithium in the function of gamma band activity mediated by PPN neurons.…”

The Critical Role of Intrinsic Membrane Oscillations

“…We discovered that every PPN neuron exhibited gamma band activity via high threshold, voltage-dependent calcium channels [48]. Later, we found that ~50% of the cells have both P/Q-and N-type calcium channels, while ~25% have only one of the two channels [49]. Early studies (reviewed in [50]), had shown that PPN neurons fire in relation to states of arousal such as "Wake-REM on" cells firing during both waking and REM sleep, while others fire only during waking called "Wake on" cells, and "REM on" cells fire only during REM sleep.…”

Participation of the pedunculopontine tegmental nucleus in arousal-demanding functions

“…Thus, the PPTg, through each of its neuronal populations, has distinct roles in promoting waking and non-REM sleep and in modulating cortical activation and muscle tone in waking and non-REM sleep [75]. The presence of different types of high threshold calcium channels in some PPTg neurons have been proposed to modulate waking (P/Qtype), while the presence of other channels (N-type) are thought to maintain REM sleep [83,84].…”