The carotid body and arousal in the fetus and neonate

Bayliss

2015

Neuron

391

332

Summary Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state-dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, “central command” and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation.

Section: Serotonergic Neurons and Sudden Infant Death Syndrome (Sids)mentioning

confidence: 99%

Neural Control of Breathing and CO2 Homeostasis

Bayliss

2015

Neuron

391

332

“…A defect in asphyxia-induced arousal probably contributes to a fraction of SIDS cases [for recent reviews, see (71)] although other causes of death are also being considered (see above-mentioned reviews). The failure to arouse may prevent a life-saving shift in body position during sleep that would free obstructed airways.…”

Section: Sids Central Oxygen Sensing Gasping and Autoresuscitationmentioning

confidence: 99%

Regulation of Breathing and Autonomic Outflows by Chemoreceptors

Comprehensive Physiology

2014

276

293

Lung ventilation fluctuates widely with behavior but arterial PCO2 remains stable. Under normal conditions, the chemoreflexes contribute to PaCO2 stability by producing small corrective cardiorespiratory adjustments mediated by lower brainstem circuits. Carotid body (CB) information reaches the respiratory pattern generator (RPG) via nucleus solitarius (NTS) glutamatergic neurons which also target rostral ventrolateral medulla (RVLM) presympathetic neurons thereby raising sympathetic nerve activity (SNA). Chemoreceptors also regulate presympathetic neurons and cardiovagal preganglionic neurons indirectly via inputs from the RPG. Secondary effects of chemoreceptors on the autonomic outflows result from changes in lung stretch afferent and baroreceptor activity. Central respiratory chemosensitivity is caused by direct effects of acid on neurons and indirect effects of CO2 via astrocytes. Central respiratory chemoreceptors are not definitively identified but the retrotrapezoid nucleus (RTN) is a particularly strong candidate. The absence of RTN likely causes severe central apneas in congenital central hypoventilation syndrome. Like other stressors, intense chemosensory stimuli produce arousal and activate circuits that are wake- or attention-promoting. Such pathways (e.g., locus coeruleus, raphe, and orexin system) modulate the chemoreflexes in a state-dependent manner and their activation by strong chemosensory stimuli intensifies these reflexes. In essential hypertension, obstructive sleep apnea and congestive heart failure, chronically elevated CB afferent activity contributes to raising SNA but breathing is unchanged or becomes periodic (severe CHF). Extreme CNS hypoxia produces a stereotyped cardiorespiratory response (gasping, increased SNA). The effects of these various pathologies on brainstem cardiorespiratory networks are discussed, special consideration being given to the interactions between central and peripheral chemoreflexes.

“…A defect in asphyxia-induced arousal possibly contributes to a fraction of SIDS cases (for recent reviews:(Kinney and Thach, 2009; Duncan et al, 2010; Darnall, 2013; Porzionato et al, 2013)) although many other causes of death are also being considered (see above mentioned reviews). The failure to arouse may be partly related to a dysfunction of peripheral and /or central chemoreceptors.…”

Section: Sudden Infant Death Syndrome Chemoreceptors and Arousalmentioning

confidence: 99%

Chemoreception and asphyxia-induced arousal

Respiratory Physiology & Neurobiology

Abbott

2013

Arousal protects against the adverse and potentially fatal effects of asphyxia during sleep. Asphyxia stimulates the carotid bodies and central chemoreceptors but the sequence of events leading to arousal is uncertain. In this review, the theoretical mechanisms leading to arousal from sleep are briefly summarized and the issue of whether central respiratory chemoreceptors (CRCs) or other types of CO2-responsive CNS neurons contribute to asphyxia-induced arousal is discussed. We focus on the role of the retrotrapezoid nucleus, the raphe and the locus coeruleus and emphasize the anatomical and neurophysiological evidence which suggests that these putative central chemoreceptors could contribute to arousal independently of their effects on breathing. Finally, we describe recent attempts to test the contribution of specific brainstem pathways to asphyxia-induced arousal using optogenetic and other tools and the possible contribution of a group of hypoxia-sensitive brainstem neurons (the C1 cells) to breathing and arousal.