The locus coeruleus and central chemosensitivity

Abstract

The locus coeruleus (LC) lies in the dorsal pons and supplies noradrenergic (NA) input to many regions of the brain, including respiratory control areas. The LC may provide tonic input for basal respiratory drive and is involved in central chemosensitivity since focal acidosis of the region stimulates ventilation and ablation reduces CO 2 -induced increased ventilation. The output of LC is modulated by both serotonergic and glutamatergic inputs. A large percentage of LC neurons are intrinsically activated by hypercapnia. This percentage and the magnitude of their response are highest in young neonates and decrease dramatically after postnatal day P10. The cellular bases for intrinsic chemosensitivity of LC neurons are comprised of multiple factors, primary among them being reduced extracellular and intracellular pH, which inhibit inwardly rectifying and voltage-gated K + channels, and activate L-type Ca 2+ channels. Activation of K Ca channels in LC neurons may limit their ultimate response to hypercapnia. Finally, the LC mediates central chemosensitivity and contains pH-sensitive neurons in amphibians, suggesting that the LC has a long-standing phylogenetic role in respiratory control.

Temperature influences neuronal activity and CO2/pH sensitivity of locus coeruleus neurons in the bullfrog,Lithobates catesbeianus

“…The locus coeruleus (LC) is a chemosensitive area within the brain stem that is used for ventilatory control in amphibians (19). Focal acidification of the LC increases minute ventilation in vivo, while ablation attenuates the hypercapnic ventilatory response by abolishing increases in tidal volume (41).…”

Effect of temperature on chemosensitive locus coeruleus neurons of Savannah monitor lizardsVaranus exanthematicus

“…In mammals, LC neurons are of particular interest for CO 2 challenges as >80% of these neurons respond to HA by increasing their firing rate (Filosa et al, 2002;Oyamada et al, 1998;Pineda and Aghajanian, 1997). A CO 2 -chemosensitive LC region may be conserved across vertebrates as it has been described in bullfrogs, toads and rats (Gargaglioni et al, 2010; and . As in mammals, more than 80% of LC neurons in bullfrogs are CO 2 activated , reinforcing its importance as a site for central chemoreception in anurans (Noronha-de-Souza et al, 2006).…”

“…Nevertheless, at least one chemosensitive region, the locus coeruleus (LC), has been described in amphibians (toads and bullfrogs: Noronha-de-Souza et al, 2006; and mammals (reviewed in Gargaglioni et al, 2010), suggesting that CO 2 /pH chemosensitivity of the LC may be conserved across air-breathing vertebrates. Anatomical studies have identified noradrenergic cells of the LC in a variety of reptiles (Kiehn et al, 1992;Lopez et al, 1992;Smeets and González, 2000;Wolters et al, 1984), including savannah monitor lizard brainstems (Wolters et al, 1984), showing tyrosine hydroxylase-containing cell bodies in the LC neurons as observed in anurans and rats (Biancardi et al, 2008;Noronha-de-Souza et al, 2006).…”

Measurement of purine release with microelectrode biosensors

“…In the brain, it is clear that the ventral surface of the medulla oblongata (VMS) contains at least some of the central chemoreceptors; however, other nuclei such as the locus coeruleus have also been proposed [41,42]. At the VMS, Loeschcke and Mitchell proposed rostral, intermediate and caudal chemosensitive areas [43,44].…”