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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. [ABSTRACT FROM AUTHOR]

The relationship between arousal, perception, and visual neglect was examined in this case study. Cold pressor stimulation (CPS: immersing the foot in iced water) was used to manipulate arousal and to determine its effects on contralesional neglect, perception of stimulus intensity (magnitude estimation), reaction time, and an electrophysiological correlate of ascending reticular activating system activity (i.e., the P50 potential). Measures that normalized from baseline following CPS included contralesional neglect on a clock drawing test, perception of stimulus magnitude, and P50 amplitude. The P50 amplitude returned to its abnormally low baseline level 20 min after CPS ended, indicating that CPS increased arousal. [ABSTRACT FROM PUBLISHER]

One element of the reticular activating system (RAS) is the pedunculopontine nucleus (PPN), which projects to the thalamus to trigger thalamocortical rhythms and the brainstem to modulate muscle tone and locomotion. The PPN is a posterior midbrain site known to induce locomotion in decerebrate animals when activated at 40-60 Hz, and has become a target for DBS in disorders involving gait deficits. We developed a research program using brainstem slices containing the PPN to study the cellular and molecular organization of this region. We showed that PPN neurons preferentially fire at gamma band frequency (30-60 Hz) when maximally activated, accounting for the effects of electrical stimulation. In addition, we developed the P13 midlatency auditory evoked potential, which is generated by PPN outputs, in freely moving rats. This allows the study of PPN cellular and molecular mechanisms in the whole animal. We also study the P50 midlatency auditory evoked potential, which is the human equivalent of the rodent P13 potential, allowing us to study PPN-related processes detected in vitro, confirmed in the whole animal, and tested in humans. Previous findings on the P50 potential in PD suggest that PPN output in this disorder is overactive. This translational research program led to the discovery of a novel mechanism of sleep-wake control based on electrical coupling, pointing the way to a number of new clinical applications in the development of novel stimulants (e.g., modafinil) and anesthetics. In addition, it provides methods for monitoring therapeutic efficacy of DBS in humans and animal models. [ABSTRACT FROM AUTHOR]

Sopite syndrome, characterized by loss of initiative, sensitivity to normally innocuous sensory stimuli, and impaired concentration amounting to a sensory gating deficit, is commonly associated with Space Motion Sickness (SMS). The amplitude of the P50 potential is a measure of level of arousal, and a paired-stimulus paradigm can be used to measure sensory gating. We used the rotary chair to elicit the sensory mismatch that occurs with SMS by overstimulating the vestibular apparatus. The effects of rotation on the manifestation of the P50 midlatency auditory evoked response were then assessed as a measure of arousal and distractibility. Results showed that rotation-induced motion sickness produced no change in the level of arousal but did produce a significant deficit in sensory gating, indicating that some of the attentional and cognitive deficits observed with SMS may be due to distractibility induced by decreased habituation to repetitive stimuli. [ABSTRACT FROM AUTHOR]

The P13 mid-latency auditory evoked potential in Rat is a sleep state-dependent response thought to be equivalent to the human P50 potential, a measure of the output of the reticular activating system. The amplitude of these potentials can be considered a measure of level of arousal, while, using a paired stimulus paradigm, the degree of habituation of the responses also can be assessed. Different durations of rotation were found to reduce the amplitude of the P13 potential, which recovered in a duration-dependent manner. Different durations of rotation led to decreases in habituation of the P13 potential again in a duration-dependent manner. These results suggest that rotation may affect the level of arousal as well as habituation to repetitive sensory inputs. Such effects could be interpreted to imply the presence, following rotation of sufficient duration, of a deficit in sensory gating, or distractibility, and are relevant for the study of the effects of space motion sickness. [ABSTRACT FROM AUTHOR]

The reticular activating system (RAS) is not an amorphous region but distinct nuclei with specific membrane properties that dictate their firing during waking and sleep. The locus coeruleus and raphe nucleus fire during waking and slow wave sleep, with the pedunculopontine nucleus (PPN) firing during both waking and REM sleep, the states manifesting arousal-related EEG activity. Two important discoveries in the PPN in the last 10 years are, 1) that some PPN cells are electrically coupled, and 2) every PPN cell manifests high threshold calcium channels that allow them to oscillate at beta/gamma band frequencies. The role of arousal in drug abuse is considered here in terms of the effects of drugs of abuse on these two mechanisms. Drug abuse and the perception of withdrawal/relapse are mediated by neurobiological processes that occur only when we are awake, not when we are asleep. These relationships focus on the potential role of arousal, more specifically of RAS electrical coupling and gamma band activity, in the addictive process as well as the relapse to drug use. [ABSTRACT FROM AUTHOR]