The Locus coeruleus (LC) has been suggested as a CO(2) chemoreceptor site in mammals. In the present study, we assessed the role of LC noradrenergic neurons in the cardiorespiratory and thermal responses to hypercapnia. To selectively destroy LC noradrenergic neurons, we administered 6-hydroxydopamine (6-OHDA) bilaterally into the LC of male Wistar rats. Control animals had vehicle (ascorbic acid) injected (sham group) into the LC. Pulmonary ventilation (plethysmograph), mean arterial pressure (MAP), heart rate (HR), and body core temperature (T (c), data loggers) were measured followed by 60 min of hypercapnic exposure (7% CO(2) in air). To verify the correct placement and effectiveness of the chemical lesions, tyrosine hydroxylase immunoreactivity was performed. Hypercapnia caused an increase in pulmonary ventilation in all groups, which resulted from increases in respiratory frequency and tidal volume (V (T)) in sham-operated and 6-OHDA-lesioned groups. The hypercapnic ventilatory response was significantly decreased in 6-OHDA-lesioned rats compared with sham group. This difference was due to a decreased V (T) in 6-OHDA rats. LC chemical lesion or hypercapnia did not affect MAP, HR, and T (c). Thus, we conclude that LC noradrenergic neurons modulate hypercapnic ventilatory response but play no role in cardiovascular and thermal regulation under resting conditions.

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Our results suggest, for the first time, that TRPV4 channel is involved in the recruitment of behavioural and autonomic warmth-defence responses to regulate core body temperature.

We assessed the role of NK-1 receptors (NK1R) expressing neurons in the locus coeruleus (LC) on cardiorespiratory responses to hypercapnia. To this end, we injected substance P-saporin conjugate (SP-SAP) to kill NK-1 immunoreactive (NK1R-ir) neurons or SAP alone as a control. Immunohistochemistry for NK1R, tyrosine hydroxylase (TH-ir) and Glutamic Acid Decarboxylase (GAD-ir) were performed to verify if NK1R-expressing neurons, catecholaminergic and/or GABAergic neurons were eliminated. A reduced NK1R-ir in the LC (72%) showed the effectiveness of the lesion. SP-SAP lesion also caused a reduction of TH-ir (66%) and GABAergic neurons (70%). LC SP-SAP lesion decreased by 30% the ventilatory response to 7% CO(2) and increased the heart rate (fH) during hypercapnia but did not affect MAP. The present data suggest that different populations of neurons (noradrenergic, GABAergic, and possibly others) in the LC express NK1R modulating differentially the hypercapnic ventilatory response, since catecholaminergic neurons are excitatory and GABAergic ones are inhibitory. Additionally, NK1R-ir neurons in the LC, probably GABAergic ones, seem to modulate fH during CO(2) exposure, once our previous data demonstrated that catecholaminergic lesion does not affect this variable.

The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. This nucleus is a mesencephalic structure of the amphibian brain and is probably homologous to the LC in mammals. There are no data available for the role of LC in the central chemoreception of amphibians. Thus the present study was designed to investigate whether LC of toads (Bufo schneideri) is a CO 2/H ϩ chemoreceptor site. Fos immunoreactivity was used to verify whether the nucleus is activated by hypercarbia (5% CO2 in air). In addition, we assessed the role of noradrenergic LC neurons on respiratory and cardiovascular responses to hypercarbia by using 6-hydroxydopamine lesion. To further explore the role of LC in central chemosensitivity, we examined the effects of microinjection of solutions with different pH values (7.2, 7.4, 7.6, 7.8, and 8.0) into the nucleus. Our main findings were that 1) a marked increase in c-fos-positive cells in the LC was induced after 3 h of breathing a hypercarbic gas mixture; 2) chemical lesions in the LC attenuated the increase of the ventilatory response to hypercarbia but did not affect ventilation under resting conditions; and 3) microinjection with acid solutions (pH ϭ 7.2, 7.4, and 7.6) into the LC elicited an increased ventilation, indicating that the LC of toads participates in the central chemoreception.ventilation; midbrain; brain stem; amphibian; isthmus; bufo; hypercarbia IT IS WELL ESTABLISHED THAT vertebrates display respiratory responses to changes in the arterial blood gases, and the underlying control mechanisms are very similar among different taxa. The transition of amphibians to air breathing was accompanied by an increase in the sensitivity to CO 2 /H ϩ (45). Interestingly, the ontogenetic changes of anuran amphibians involve modifications of the control system from being almost entirely oxygen driven to a combination of acid-base and oxygen driven (11).Central respiratory CO 2 chemoreceptors have been clearly established in adult anuran amphibians (8,46), and these receptors are probably distributed throughout the rostral medulla, surrounding the fourth ventricle (50). In mammals, these receptors were once thought to be located only close to the surface of the ventral medulla, but it is now clear that they are widespread within the brainstem (12). Recently, sites have been identified in the ventrolateral medulla, nucleus of the solitary tract, ventral respiratory group, locus coeruleus (LC), caudal medullary raphe, and fastigial nucleus of the cerebellum (for a review, see Ref. 35). However, it remains unclear whether chemoreceptors are also widely distributed in amphibians. An evaluation of specific contributions of these chemosensitive sites can be achieved by CO 2 challenge, focal stimulation, or focal disruption. Focal acidification of a single central chemosensitive site increases ventilation, whereas disruption decreases ventilation (3,28,37,47). According to Nattie (35), the presence of widespread central chemoreceptors may be related to the increased demands of a...