c-Fos expression in the midbrain periaqueductal gray after chemoreceptor and baroreceptor activation

Abstract

The pattern of Fos-like immunoreactivity (FLI) in the periaqueductal gray (PAG) associated with activation of arterial chemoreceptors versus baroreceptor afferents was examined in urethane-anesthetized rats. Chemoreflex responses elicited by repeat intravenous injections of potassium cyanide (KCN; 90 microg/kg) significantly increased FLI in all columns of the PAG relative to saline-injected animals. Pressor responses elicited by intravenous phenylephrine (PE) produced a similar pattern of increased FLI throughout the PAG except in the dorsomedial and lateral columns of the caudal PAG, where FLI was minimal. Chemoreflex responses were unaltered by blockade of excitatory amino acid receptors in the dorsomedial PAG, and < 10% of the neurons of the caudal PAG that expressed FLI after KCN stimulation were retrogradely labeled from the A5 region of the caudal ventrolateral pons. These results indicate that integration of chemoreceptor inputs occurs primarily in the dorsal and lateral columns of the caudal PAG, but these neurons have little direct descending influence over lower brain stem regions integral to the central arterial chemoreflex arc.

Translational approach to studying panic disorder in rats: Hits and misses

“…Chemoreceptor stimulations with KCN induced c-Fos expression chiefly in the caudal sectors of the DPAG (Hayward and Von Reitzentstein, 2002). Hayward and Von Reitzentstein (2002) showed that less than 10% of the neurons of the caudal PAG that expressed c-Fos after KCN injections were retrogradely labelled from the A5 region of the pons that is believed to mediate the pressor component of the chemoreceptor reflex (Guyenet and Koshiya, 1995). Moreover, Haibara et al (2002) showed that the microinjection of lidocaine in the LPBA attenuated the cardiovascular reflex responses to KCN injections, whereas those in DLPAG and LPAG were ineffective.…”

“…Exceptions included jumping, which was elicited in one rat only, and defecation and micturition, for which the effective doses were unusually low, compared with the high thresholds of these responses in electrical and chemical stimulations of the DPAG. Because KCN-induced defensive behaviours are suppressed by both sinoaortic denervation and glomus artery ligation (Franchini and Krieger, 1993;Franchini et al, 1997), these behaviours are mediated by the NTS efferents to the DPAG (Bandler and Tork, 1987;Hayward and Von Reitzentstein, 2002;Loewy and Burton, 1978). The chemoreceptor-mediation of the KCN-evoked defensive behaviours is further supported by the rather short latencies (1-3 s) of these responses.…”

“…Reciprocally, the electrical stimulation of the PAG and the hypothalamus defence areas was shown to facilitate chemoreceptor-mediated hyperventilation to both KCN and dinitrophenol (Hilton and Joels, 1965). Chemoreceptor stimulations with KCN induced c-Fos expression chiefly in the caudal sectors of the DPAG (Hayward and Von Reitzentstein, 2002). Hayward and Von Reitzentstein (2002) showed that less than 10% of the neurons of the caudal PAG that expressed c-Fos after KCN injections were retrogradely labelled from the A5 region of the pons that is believed to mediate the pressor component of the chemoreceptor reflex (Guyenet and Koshiya, 1995).…”

“…In addition, they suggest that the LPBA, but not the DPAG, mediates the cardiovascular reflex to the KCN excitation of chemoreceptors. Although the experiments of Hayward and Von Reitzentstein (2002) were performed in urethane-anesthetised rats, these authors suggested that the most important role of the chemoreceptor-sensitive neurons of the caudal DPAG is in conveying information to the forebrain and/or coordinating the escape behaviour associated with the chemoreceptor reflex. Lastly, these results suggest that respiratory-like panic attacks are largely mediated by the DPAG projections to the LPBA, a component of the pontine 'pneumotaxic centre'.…”

Towards a translational model of panic attack.

“…Overall, these results support the chemoreceptor facilitation of DPAG-evoked defensive behaviors and, reciprocally, the DPAG facilitation of chemoreceptor ventilatory reflex. More important, however, because Hayward and von Reitzentstein (2002) carried out their experiments in urethane anesthetized rats, KCN activation of DPAG was not secondary to emotional responses. Rather, they suggest the DPAG intrinsic sensitivity to hypoxic states.…”