Eugene Nattie

..Orexin-mediated processes may operate at two levels: (1) in sleep-wake and circadian states and (2) in stress, for example, the defense or "fight-or-flight" response and panic-anxiety syndrome...

..They affect physiological control systems in many ways, perhaps not all measurable, via the study of the steady-state CO2 response...

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..NK1R-ir neurons in the ventral medulla are essential for normal central chemoreception, provide a drive to breathe, and modulate the peripheral chemoreceptor responses. These effects are not state dependent...

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..We comment on the organization of this distributed central chemoreceptor system and suggest that interactions among sites are synergistic and not additive, which is an important aspect of its normal function...

..Emphasis is placed on the importance of data derived from studies performed in the absence of anesthesia...

..001; two-way ANOVA; P < 0.05, Tukey's post hoc test). We conclude that separate populations of serotonergic and adjacent NK1R-expressing neurones in the medulla are both involved in central chemoreception in vivo...

..The lack of effect on the response to systemic hypercapnia suggests that the RTN provides an ongoing endogenous drive to respiration by a process that is independent of its role in chemoreception...

..Central chemoreceptors in the NTS affect breathing in both sleep and wakefulness. The threshold for arousal in caudal NTS is greater than that for the stimulation of breathing...

..In the awake rat, the RTN region provides a portion of the tonic drive to breathe, as well as a portion of the response to hypercapnia...

..For example, some sites are more important in wakefulness; others in sleep. Proof for these hypotheses depends critically on obtaining accurate measures of stimulus intensity at each chemoreceptor site in vivo...

..1978. Science 201, 16-22). The presence of a number of chemosensitive sites with varying thresholds, sensitivity, and arousal dependence provides finely tuned control and stability for breathing...

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..Regional differences in pHi regulation between cortex and ventral medulla may be due to both chemosensitive and non-chemosensitive neurons...

..We conclude that neurons with NK1R-ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal...

..We conclude that OX(1)R in the rostral medullary raphe contribute to the hypercapnic chemoreflex in wakefulness, during the dark period in rats...

..Inhibition of serotonergic medullary raphé and extra-raphé neurons decreases ventilatory CO2 sensitivity and alters cardiovascular variables and sleep cycling, which may contribute to the sudden infant death syndrome...

..In the Cool condition the ventilatory response to hypoxia is inhibited but appropriately so for the lower VO2 ...

..We conclude that CA neurones (1) promote wakefulness, (2) participate in central respiratory chemoreception, (3) stimulate breathing frequency, and (4) minimize breathing variability in REM sleep...

..007). Within the first two postnatal weeks, the medullary 5-HT system plays an important role in cardiorespiratory control, mitigating spontaneous bradycardia, stabilizing the breathing pattern, and dampening the hypercapnic Ve response...

..These effects of caudal MR serotonergic neurons could be at a chemoreceptor site, e.g. the RTN, or at 'downstream' sites involved in rhythm and pattern generation...

..Conclusions: Central CA neurons have a net excitatory effect on breathing and chemoreception but a net inhibitory effect on blood pressure...

..9 (0.7) Torr (N=5), which may inhibit other chemoreceptor sites. Multiple chemoreceptor sites may interact to provide high sensitivity in systemic hypercapnia and stability during heterogeneous stimulation and inhibition...

..This genetic model allows examination of the role of excess 5-HT in ECF in the development of the control of breathing and central chemoreception, which may be pertinent to SIDS...

..Other sources of input include the Kölliker-fuse nucleus, subceruleus, A5 region, and the paralemniscal zone...

..Physiol. 586.9, 2321-2329, 2008) appears to have origins in early postnatal life (P15) when ventilation in both air and 5% CO(2) is reduced...

..In addition, this approach should be useful to study unrestrained neonatal mice under conditions where body temperature approaches environmental temperature and barometric plethysmography cannot be used...

..Disturbances of medullary raphé function can alter central chemoreception and normal sleep architecture, which may contribute to the pathogenesis of SIDS...

..Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons...

..We conclude that serotonergic activity in the MRR plays a role in the ventilatory response to hypercapnia, but not to hypoxia, and that MRR 5-HT1A receptors are also involved in thermoregulation and arousal...

..The results support our hypothesis that the orexin system participates importantly in central chemoreception in a vigilance-state- and diurnal-cycle-dependent manner and indicate a role for orexin in the important process of sighing...

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..We conclude that projections of orexin-containing neurons to the RTN contribute, via OX(1)Rs in the region, to the hypercapnic chemoreflex control during wakefulness and to a lesser extent, non-rapid eye movement sleep...

..Nevertheless, the description of an animal model with serotonin defects that has autonomic dysfunction and spontaneous mortality at a young age is an exciting finding of possible importance for understanding SIDS...

..These results suggest that PF-LHA functions as a central chemoreceptor site in the central nervous system in a vigilant state dependent manner with predominant effects in wakefulness...

..Neurons with appropriate chemosensitivity are spread throughout the brainstem; their individual properties and collective role are just beginning to be understood...

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..Abnormal central chemoreception is a key defect in the congenital central hypoventilation syndrome and is hypothesized to play a role in the Sudden Infant Death Syndrome. ..