The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control

Martelli, Davide; Stanić, Davor; Dutschmann, Mathias

doi:10.1016/j.resp.2013.06.019

Cited by 36 publications

(23 citation statements)

References 98 publications

(111 reference statements)

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“…In SIDS there is a reduction of serotonin content in the hypothalamus [94] which could be indicative of reduced feedback from the DR (one of the main site of serotonin production) which has been found to have altered serotonergic expression in SIDS [27,53,64]. Finally, we also noted reduced orexinergic fibres in the MPB, part of the parabrachial complex, which also contributes to REM/non-REM sleep [70].…”

Section: Dysfunctional Sleepsupporting

confidence: 54%

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

et al. 2015

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Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.

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Section: Dysfunctional Sleepsupporting

confidence: 54%

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

et al. 2015

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“…The pontine respiratory regions include the Kölliker–Fuse nucleus (KF) and the parabrachial complex (PB) in the dorsolateral pons, which are assumed to be the most important regions in the regulation of respiratory activity and respiratory phase transition [104–107], as well as several areas in the ventrolateral pons. These pontine structures interact with multiple medullary respiratory centers and regulate respiratory activity [104]. For instance, the A5 noradrenergic neurons are presumed to send inhibitory synaptic inputs to the respiratory rhythm generators in the medulla [108, 109].…”

Section: Section 6: the Functional Involvement Of The Pons In The Resmentioning

confidence: 99%

The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology

et al. 2016

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Respiratory activities are produced by medullary respiratory rhythm generators and are modulated from various sites in the lower brainstem, and which are then output as motor activities through premotor efferent networks in the brainstem and spinal cord. Over the past few decades, new knowledge has been accumulated on the anatomical and physiological mechanisms underlying the generation and regulation of respiratory rhythm. In this review, we focus on the recent findings and attempt to elucidate the anatomical and functional mechanisms underlying respiratory control in the lower brainstem and spinal cord.Electronic supplementary materialThe online version of this article (doi:10.1007/s12576-016-0475-y) contains supplementary material, which is available to authorized users.

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“…In support of this proposal, much evidence, both anatomical and functional, can be mustered: (i) The MnPO sends projections to the perifornical region of the lateral hypothalamic area, the dorsal raphé nuclei, the locus coeruleus and the parabrachial nucleus, key components of the neuronal regulatory arousal system (Martelli et al . ), and also to the ventrolateral preoptic nucleus (VLPO), an important area for the regulation of sleep occurrence (Sherin et al . , Saper et al .…”

Section: Sleepmentioning

confidence: 99%

“…The model arising from this scenario is of the MnPO becoming active after a prolonged period of wakefulness to regulate the inactivation of the brain areas responsible for the maintenance of wakefulness. In support of this proposal, much evidence, both anatomical and functional, can be mustered: (i) The MnPO sends projections to the perifornical region of the lateral hypothalamic area, the dorsal raph e nuclei, the locus coeruleus and the parabrachial nucleus, key components of the neuronal regulatory arousal system (Martelli et al 2013), and also to the ventrolateral preoptic nucleus (VLPO), an important area for the regulation of sleep occurrence (Sherin et al 1996, Saper et al 2005, Uschakov et al 2007). (ii) The inhibition of the MnPO, by means of microinjections of muscimol (GABAa agonist), induces Fos expression in hypocretin-(orexin) and serotonin-containing neurones, in the perifornical lateral hypothalamic area and in the dorsal raph e, respectively, in the anaesthetized rat (Kumar et al 2008).…”

Section: Sleepmentioning

confidence: 99%

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis

et al. 2015

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Located in the midline anterior wall of the third cerebral ventricle (i.e. the lamina terminalis), the median preoptic nucleus (MnPO) receives a unique set of afferent neural inputs from fore-, mid- and hindbrain. These afferent connections enable it to receive neural signals related to several important aspects of homeostasis. Included in these afferent projections are (i) neural inputs from two adjacent circumventricular organs, the subfornical organ and organum vasculosum laminae terminalis, that respond to hypertonicity, circulating angiotensin II or other humoural factors, (ii) signals from cutaneous warm and cold receptors that are relayed to MnPO, respectively, via different subnuclei in the lateral parabrachial nucleus and (iii) input from the medulla associated with baroreceptor and vagal afferents. These afferent signals reach appropriate neurones within the MnPO that enable relevant neural outputs, both excitatory and inhibitory, to be activated or inhibited. The efferent neural pathways that proceed from the MnPO terminate on (i) neuroendocrine cells in the hypothalamic supraoptic and paraventricular nuclei to regulate vasopressin release, while polysynaptic pathways from MnPO to cortical sites may drive thirst and water intake, (ii) thermoregulatory pathways to the dorsomedial hypothalamic nucleus and medullary raphé to regulate shivering, brown adipose tissue and skin vasoconstriction, (iii) parvocellular neurones in the hypothalamic paraventricular nucleus that drive autonomic pathways influencing cardiovascular function. As well, (iv) other efferent pathways from the MnPO to sites in the ventrolateral pre-optic nucleus, perifornical region of the lateral hypothalamic area and midbrain influence sleep mechanisms.

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The emerging role of the parabrachial complex in the generation of wakefulness drive and its implication for respiratory control

Cited by 36 publications

References 98 publications

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

The respiratory control mechanisms in the brainstem and spinal cord: integrative views of the neuroanatomy and neurophysiology

The median preoptic nucleus: front and centre for the regulation of body fluid, sodium, temperature, sleep and cardiovascular homeostasis

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