Medullary serotonin neurons and central CO2 chemoreception

Abstract

Serotonergic (5-HT) neurons are putative central respiratory chemoreceptors, aiding in the brain's ability to detect arterial changes in P CO 2 and implement appropriate ventilatory responses to maintain blood homeostasis. These neurons are in close proximity to large medullary arteries and are intrinsically chemosensitive in vitro, characteristics expected for chemoreceptors. 5-HT neurons of the medullary raphé are stimulated by hypercapnia in vivo, and their disruption results in a blunted hypercapnic ventilatory response. More recently, data collected from transgenic and knock-out mice have provided further insight into the role of 5-HT in chemosensitivity. This review summarizes current evidence in support of the hypothesis that 5-HT neurons are central chemoreceptors, and addresses arguments made against this role. We also briefly explore the relationship between the medullary raphé and another chemoreceptive site, the retrotrapezoid nucleus, and discuss how they may interact during hypercapnia to produce a robust ventilatory response.

Central serotonin neurons are required for arousal to CO 2

“…It has previously been shown that 5-HT neurons are required for a normal ventilatory response to hypercapnia (9,13,29,30). The results presented here indicate that 5-HT neurons are also required for a normal arousal response to hypercapnia.…”

“…In vitro studies have shown that a subset of 5-HT neurons in both the medullary and midbrain raphé increases firing rate in response to a rise in CO 2 or decrease in pH (9). When studied in unanesthetized behaving mammals, similar results have been obtained in vivo by multiple groups (9).…”

“…However, in contrast to the data described above for 5-HT neurons in the raphé nuclei in behaving unanesthetized animals, these nonresponsive 5-HT neurons were located in the ventrolateral medulla and were recorded under anesthesia, which has major effects on breathing. The bulk of the existing data is in favor of the hypothesis that 5-HT neurons are central chemoreceptors, as discussed in a recent review (9).…”

Breathing without CO2Chemosensitivity in ConditionalPhox2bMutants

“…Another possibility is that the RTN is an obligatory intermediate for funneling input from other central chemoreceptors to the RRG early but not later in life, although experimental evidence for this is still lacking. Candidate chemoreceptor sites are serotonergic neurons that have been reported to be virtually pH-insensitive at birth and to become fully operational only beyond the newborn period (Wang and Richerson, 1999;Corcoran et al, 2009) but also glial cells (Gourine et al, 2010;Wenker et al, 2010). The latter respond to low pH already in young postnatal rats and may act mainly via RTN neurons, but additional pathways may come into play in adulthood.…”

Apnea of prematurity: pathogenesis and management strategies

“…Serotonergic (5-HT) neurons, located in the rostral ventrolateral medulla, are putative central chemoreceptors. There is compelling evidence now that there are multiple additional sites of central chemoreception 5 (see for a review). Ventilatory response to CO 2 is significantly reduced in preterm infants but increases with advancing postnatal age.…”