( 16) more than 30 years ago, have received relatively little attention ( 9– 11, 46, 53) despite evidence from other brain regions that glial cells can function as important modulators of both neural network activity and vascular tone ( 25). Surprisingly, pH-sensitive RTN glial cells, first described by Fukuda et al. In this review, we will summarize the properties of chemosensitive RTN neurons further details on this topic can be found in several recent reviews ( 23, 24, 41). Although the relative contributions of these putative chemoreceptor regions remains controversial ( 24, 42), there is compelling evidence that the RTN is an important site of chemoreception ( 1, 6, 26, 38, 43). ![]() Several brain regions are thought to participate in chemoreception including the nucleus tractus solitarius, locus coeruleus, medullary raphe, prebotzinger complex, fastigial nucleus of the cerebellum, hypothalamus, and retrotrapezoid nucleus (RTN) ( 14, 22). ![]() In this review, we will summarize the defining characteristics of pH-sensitive neurons and discuss potential contributions of pH-sensitive glial cells as both a source of purinergic drive to pH-sensitive neurons and a modulator of vasculature tone.Ĭentral chemoreception is the mechanism by which the brain regulates breathing in response to changes in tissue pH, wherein CO 2/H + chemoreceptors sense pH changes to regulate the depth and frequency of breathing. It is well established in vivo that changes in cerebral blood flow can profoundly affect the chemoreflex ( 2) e.g., limiting blood flow by vasoconstriction acidifies tissue pH and increases the ventilatory response to CO 2, whereas vasodilation can wash out metabolically produced CO 2 from tissue to increase tissue pH and decrease the stimulus at chemoreceptors. A third, potentially important, aspect of RTN chemoreception is the regulation of blood flow, which is an important determinate of tissue pH and consequently chemoreceptor activity. A region of the brain stem called the retrotrapezoid nucleus (RTN) is thought to be an important site of chemoreception ( 23), and recent evidence suggests that RTN chemoreception involves two interrelated mechanisms: H +-mediated activation of pH-sensitive neurons ( 38) and purinergic signaling ( 19), possibly from pH-sensitive glial cells. ![]() Central chemoreception is the mechanism by which CO 2/pH-sensitive neurons (i.e., chemoreceptors) regulate breathing in response to changes in tissue pH.
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