The Brain Nucleus Locus Coeruleus: Restricted Afferent Control of a Broad Efferent Network

Aston‐Jones, Gary; Ennis, Matthew; Pieribone, Vincent A.; Nickell, William T.; Shipley, MT

doi:10.1126/science.3775363

Cited by 725 publications

(295 citation statements)

References 58 publications

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“…One possible mechanism to explain the effect of metyrapone on delta sleep is that the increase in PVN CRF release affects other brain areas involved in sleep or arousal. This possibility is supported by studies that have shown that some PVN CRF neurons project to the locus ceruleus (Aston- Jones et al, 1986;Valentino et al, 1992). For example, Valentino et al (1992) showed that retrograde labeling of CRF terminals in the locus ceruleus originated in the PVN.…”

Section: Discussionmentioning

confidence: 80%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combatrelated PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.

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Section: Discussionmentioning

confidence: 80%

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Neylan

Lenoci

Maglione

et al. 2003

Neuropsychopharmacol

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“…Thus, the reduction of inhibitory inputs from the raphe nuclei to the LC after lesion of the SNc causes an increase of activity of LC noradrenergic neurons. The LC also receives excitatory glutamatergic afferents from the paragigantocellularis nucleus [20] .…”

Section: Resultsmentioning

confidence: 99%

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

et al. 2009

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Objective To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD). Methods 2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording. Results The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05). Conclusion LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.

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“…(Foote et al, 1983;Aston-Jones et al, 1986. It is worth noting that A6 neurons may also play a role in respiratory control because they display a respiratory-modulated firing, are sensitive to hypoxia, and may contribute to long-term adaptation to hypoxia (Guyenet et al, 1993;Dobbins and Feldman, 1994;Oyamada et al, 1998;Ballantyne and Scheid, 2000;Roux et al, 2000aRoux et al, , 2000b.…”

Section: Possible Contribution Of A6 Neurons To Rrg Prenatal Maturationmentioning

confidence: 99%

Phox2a Gene, A6 Neurons, and Noradrenaline Are Essential for Development of Normal Respiratory Rhythm in Mice

Viemari¹,

Bévengut²,

Burnet³

et al. 2004

J. Neurosci.

103

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Although respiration is vital to the survival of all mammals from the moment of birth, little is known about the genetic factors controlling the prenatal maturation of this physiological process. Here we investigated the role of the Phox2a gene that encodes for a homeodomain protein involved in the generation of noradrenergic A6 neurons in the maturation of the respiratory network. First, comparisons of the respiratory activity of fetuses delivered surgically from heterozygous Phox2a pregnant mice on gestational day 18 showed that the mutants had impaired in vivo ventilation, in vitro respiratory-like activity, and in vitro respiratory responses to central hypoxia and noradrenaline. Second, pharmacological studies on wild-type neonates showed that endogenous noradrenaline released from pontine A6 neurons potentiates rhythmic respiratory activity via ␣1 medullary adrenoceptors. Third, transynaptic tracing experiments in which rabies virus was injected into the diaphragm confirmed that A6 neurons were connected to the neonatal respiratory network. Fourth, blocking the ␣1 adrenoceptors in wild-type dams during late gestation with daily injections of the ␣1 adrenoceptor antagonist prazosin induced in vivo and in vitro neonatal respiratory deficits similar to those observed in Phox2a mutants. These results suggest that noradrenaline, A6 neurons, and the Phox2a gene, which is crucial for the generation of A6 neurons, are essential for development of normal respiratory rhythm in neonatal mice. Metabolic noradrenaline disorders occurring during gestation therefore may induce neonatal respiratory deficits, in agreement with the catecholamine anomalies reported in victims of sudden infant death syndrome.Key words: prenatal maturation of the respiratory network; Phox2a gene; fetal mice; in vivo ventilation; in vitro respiratory activity of brainstem; spinal cord preparations; noradrenaline; A6 neurons

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The Brain Nucleus Locus Coeruleus: Restricted Afferent Control of a Broad Efferent Network

Cited by 725 publications

References 58 publications

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism

Phox2a Gene, A6 Neurons, and Noradrenaline Are Essential for Development of Normal Respiratory Rhythm in Mice

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