Parabrachial neurons mediate dorsal periaqueductal gray evoked respiratory responses in the rat

Abstract

The neural substrates mediating autonomic components of the behavioral defense response reside in the periaqueductal gray (PAG). The cardiovascular components of the defense response evoked from the dorsal PAG (DPAG) have been well described and are dependent, in part, on the integrity of neurons in the region of the parabrachial nucleus as well as the rostral ventrolateral medulla. Descending pathways mediating the ventilatory response associated with activation of DPAG neurons are unknown. The present study was undertaken to test the hypothesis that parabrachial area neurons are also involved in mediating the respiratory response to DPAG stimulation. In urethane-anesthetized, spontaneously breathing rats, electrical stimulation of the DPAG significantly increased respiratory rate, arterial pressure, and heart rate. Changes in respiratory frequency were associated with significant decreases in inspiratory and expiratory durations. After bilateral inhibition of neurons in the lateral parabrachial nucleus (LPBN) region with 5 mM muscimol (n = 6), DPAG-evoked increases in respiration and heart rate were attenuated by 90 +/- 6 and 72 +/- 13%, respectively. The pressor response evoked by DPAG stimulation, however, was attenuated by only 57 +/- 6%. Bilateral blockade of glutamate receptors with 20 mM kynurenic acid (n = 6) in the LPBN also markedly attenuated DPAG-evoked increases in respiration and heart rate (65 +/- 15 and 53 +/- 9% reduction, respectively) but only modestly changed the DPAG-evoked pressor response (34 +/- 16% reduction). These results demonstrate that LPBN neurons play a significant role in the DPAG-mediated respiratory component of behavioral defense responses. This finding supports previous work demonstrating that the dorsolateral pons plays a significant role in mediating most physiological adjustments associated with activation of the DPAG.

Midbrain modulation of the cardiac baroreflex involves excitation of lateral parabrachial neurons in the rat

“…Furthermore, the effect of LPBN blockade occurred in the absence of any noticeable change in baseline baroreflex function or resting MAP and HR. Our results support previous findings demonstrating a critical role for LPBN area neurons in mediating cardiovascular responses originating from the dorsal PAG (16,32). However, because the effects of dorsal PAG stimulation on cardiac baroreflex function were only partially reversed by LPBN blockade, our results also support evidence from other investigators demonstrating that other brainstem regions outside the LPBN may be recruited during dorsal PAG stimulation for the purpose of baroreflex modulation (7,38).…”

“…Interestingly blockade of these receptor subtypes in the NTS does not evoke a parallel change in baseline baroreflex function or dorsal PAG evoked increases in baseline MAP or HR (38). In contrast, the results of the present study and a previous work (16,32) demonstrate that LPBN neurons play an important role in mediating dorsal PAG evoked increases in baseline MAP and HR, also independent of any changes in baseline baroreflex function. This suggests that changes in autonomic regulation evoked by activation of the dorsal PAG are mediated through excitation (or inhibition) of multiple descending pathways, allowing for independent control of both tonic and reflex regulation of sympathetic and parasympathetic drive.…”

“…In 1993 Nosaka and colleagues first demonstrated that large electrolytic or chemical lesions of the dorsal pons, localized to the region of the parabrachial nucleus (PBN), markedly reduced dorsal PAG evoked increases in mean arterial pressure (MAP) (32). In a more recent study from our lab, utilizing smaller microinjection volumes, we confirmed that activation of lateral PBN (LPBN) neurons was essential for dorsal PAG evoked increases in MAP and heart rate (HR), as well as changes in breath timing (16). This observation corroborated neuroanatomical data showing that dorsal PAG neurons primarily project to the LPBN and not the medial PBN (23).…”

“…In a previous study we demonstrated that chemical blockade of the LPBN markedly altered baseline respiratory timing, including increasing the time of the times of inspiration and expiration and reducing baseline respiratory frequency (16). This change in respiratory control may have independently altered baroreflex function.…”

“…In trials combining dorsal PAG stimulation with ADN stimulation, the onset of PAG stimulation preceded ADN stimulation by a minimum of 10 s. This 10 s interval was based on previous work identifying that this was the minimum amount of time needed for cardiovascular response to dorsal PAG stimulation to stabilize (16). The inter-trial interval was two minutes for the majority of the experiments and the order of ADN and PAG stimulation frequency was randomly presented between trials.…”