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Review
. 2010 Oct 31;173(3):256-63.
doi: 10.1016/j.resp.2010.03.006. Epub 2010 Mar 10.

Medullary serotonin neurons and their roles in central respiratory chemoreception

Matthew R Hodges  1 , George B Richerson
Affiliations
Review

Medullary serotonin neurons and their roles in central respiratory chemoreception

Matthew R Hodges et al. Respir Physiol Neurobiol. .

Abstract

Much progress has been made in our understanding of central chemoreception since the seminal experiments of Fencl, Loeschcke, Mitchell and others, including identification of new brainstem regions and specific neuron types that may serve as central "sensors" of CO(2)/pH. In this review, we discuss key attributes, or minimal requirements a neuron/cell must possess to be defined as a central respiratory chemoreceptor, and summarize how well each of the various candidates fulfill these minimal criteria-especially the presence of intrinsic chemosensitivity. We then discuss some of the in vitro and in vivo evidence in support of the conclusion that medullary serotonin (5-HT) neurons are central chemoreceptors. We also provide an additional hypothesis that chemosensitive medullary 5-HT neurons are poised to integrate multiple synaptic inputs from various other sources thought to influence ventilation. Finally, we discuss open questions and future studies that may aid in continuing our advances in understanding central chemoreception.

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Figures

Figure 1
Figure 1
(A) A sketch representing the estimated location(s) of the rostral (blue) and caudal (tan) chemosensitive zones originally described by Mitchell and Löeschcke, respectively. (B) Confocal images of blood vessels on the surface of the brainstem superimposed onto the midline and ventrolateral distribution of 5-HT neurons. Note that in addition to those on the midline, there are also ventrolateral areas with a high density of 5-HT neurons, underlying the classically-described chemosensitive regions. (C) There are c-fos positive neurons in the midline and on the ventral medullary surface of animals exposed to progressive hypercapnic acidosis (5, 7, and 9% CO2) that are in the same regions as 5-HT neurons. (D) A sketch of the ventral medullary surface indicating areas probed that displayed (solid circles) or did not display (open circles) hypercapnia-induced ATP release. These also correspond to the location of 5-HT neurons in both the midline and VLM. (A) Adapted from the Handbook of Physiology (Feldman, 1986). (B) Adapted from Bradley et al., Nat. Neurosci., 5(5): 401–2, 2002. (C) Adapted from Okada et al., J. Appl. Physiol. 93(2): 427–39, 2002. (D) Adapted from Spyer at al., Nature 436(7047): 108–11, 2005.
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