Helen A. Baghdoyan

A neuroanatomical gradient in the pontine tegmentum for the cholinoceptive induction of desynchronized sleep signs

Microinjection of cholinergic agonists into the pontine tegmentum was used to evoke a state which was polygraphically and behaviorally similar to desynchronized (D) sleep. This study was designed to test the hypothesis that the production of this pharmacologically induced D sleep-like state (D-ACh) was dependent upon the anatomical locus of drug administration within the pontine tegmentum. Four dependent variables of D sleep were measured: D latency, D percentage, D duration and D frequency. Multiple regression analysis and analysis of variance were performed to evaluate the relationship between the three-dimensional coordinates of the injection site (posterior, vertical and lateral) and these 4 dependent measures. The intrapontine site of drug administration accounted for a statistically significant amount of the variance in D latency, D percentage and D duration. There was no significant relationship between the anatomical site of saline injection and the dependent measures of D sleep. A significant increase in D frequency following microinjection of cholinergic agonists was found to be independent of injection site. Pontine injection sites which yielded the shortest D latencies were found to be the same sites from which the highest D percentages were evoked. Rostrodorsal pontine tegmental injection sites were most effective in producing the highest percentages of D-ACh with the shortest latencies to onset. Injections made more caudally and ventrally within the pontine tegmentum produced lower percentages of D-ACh with longer latencies to onset. These data suggest the existence of an anatomical gradient within the pontine tegmentum for the cholinoceptive evocation of a D sleep-like state, and further support the concept that D sleep is generated, in part, by pontine cholinergic mechanisms.

Pontogeniculooccipital waves: spontaneous visual system activity during rapid eye movement sleep

Summary1.Pontogeniculooccipital (PGO) waves are recorded during rapid eye movement (REM) sleep from the pontine reticular formation, lateral geniculate bodies, and occipital cortex of many species.2.PGO waves are associated with increased visual system excitability but arise spontaneously and not via stimulation of the primary visual afferents. Both auditory and somatosensory stimuli influence PGO wave activity.3.Studies using a variety of techniques suggest that the pontine brain stem is the site of PGO wave generation. Immediately prior to the appearance of PGO waves, neurons located in the region of the brachium conjunctivum exhibit bursts of increased firing, while neurons in the dorsal raphe nuclei show a cessation of firing.4.The administration of pharmacological agents antagonizing noradrenergic or serotonergic neurotransmission increases the occurrence of PGO waves independent of REM sleep. Cholinomimetic administration increases the occurrence of both PGO waves and other components of REM sleep.5.Regarding function, the PGO wave-generating network has been postulated to inform the visual system about eye movements, to promote brain development, and to facilitate the response to novel environmental stimuli.

Relevance of sleep neurobiology for cognitive neuroscience and anesthesiology

Although general anesthetics are used for approximately 21 million patients per year in the United States,1 the molecular and cellular mechanisms by which anesthetics produce loss of waking consciousness are poorly understood. The complexity of consciousness and relatively imprecise clinical signs that are used to evaluate the depth of anesthesia are significant limitations for the study of consciousness. Recent advances in sleep neurobiology continue to enhance the understanding of different physiological traits that define altered states of consciousness. The original hypothesis2 that neural networks that evolved to generate sleep are preferentially modulated by anesthetic drugs has been supported by multiple lines of evidence.3–9 These data demonstrate that sleep neurobiology can contribute to understanding the mechanisms by which anesthetics cause loss of consciousness. The goal of this chapter is to selectively review the neurobiology of sleep and wakefulness in relation to anesthesia-induced loss of consciousness.

Increased ponto-geniculo-occipital (PGO) wave frequency following central administration of neostigmine

In all mammals so far investigated the occurrence of ponto-geniculo-occipital (PGO) waves precedes the onset and maintenance of desynchronized (D) sleep. As unitary electrographic events, PGO waves provide an index for quantitative evaluation of physiological D sleep or the D sleep-like state evoked by centrally administered acetylcholinesterase inhibitors. The present study characterized PGO wave frequency and time course following central administration of neostigmine bromide (Neo). The results show that Neo produced a dose-dependent increase in PGO wave frequency and time course when injected into brainstem regions other than areas containing putative PGO wave generating neurons. These results support the concept that PGO waves and D sleep are generated by an anatomically distributed network of cholinoceptive neurons.

Opioids, Sedation, and Sleep

Sedation is an area of active research motivated by the clinical need for safe and reliable techniques. An understanding of the cellular and molecular physi-ology of sedation will contribute to the rational development of sedating drugs. These important goals are hampered, however, by the complexity of sedation as an altered State of arousal and by the diversity of sedating drugs. The purpose of this chapter is to selectively review data in support of a working hypothesis that conceptually unifies efforts to understand the neurochemical basis of sedation.