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Pontine A5 region modulation of the cardiorespiratory response evoked from the midbrain dorsolateral periaqueductal grey

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Abstract

Connections between the midbrain dorsolateral periaqueductal grey (dlPAG) and the pontine A5 region have been shown. The stimulation of both regions evokes similar cardiovascular responses: tachycardia and hypertension. Accordingly, we have studied the interactions between dlPAG and A5 region in spontaneously breathing anesthetized rats. dlPAG was electrically stimulated (20–30 μA 1-ms pulses were given for 5 s at 100 Hz). Changes in the evoked cardiorespiratoy response were analysed before and after ipsilateral microinjections of muscimol (GABAergic agonist, 50 nl, 0.25 nmol, 5 s) within the A5 region. Electrical stimulation of the dlPAG produces, in the rat, a response characterized by tachypnoea (p < 0.001), hypertension (p < 0.001) and tachycardia (p < 0.001). The increase in respiratory rate was due to a decrease in expiratory time (p < 0.01). Pharmacological inhibition of the A5 region with muscimol produced a marked reduction of the tachycardia (p < 0.001) and the tachypnoea (p < 0.01) evoked from the dlPAG. Finally, to assess functional interactions between A5 and dlPAG, extracellular activity of putative A5 neurones were recorded during dlPAG electrical stimulation. Forty A5 cells were recorded, 16 of which were affected by dlPAG stimulation (40%). 4 cells showed activation, 5 cells excitation and 7 cells decreased spontaneous activity to dlPAG stimulation (p < 0.001). These results confirm a link between the A5 region and dlPAG. The potential role of these connections in the modulation of dlPAG evoked cardiorespiratory responses and their possible clinical implications are discussed.

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Funding

The study was supported by a program grant Junta de Andalucía, Group no. CTS-156, Spain. Part of the final study was supported with a grant, PPit 2017/14, from the Own Funds Program of the University of Málaga.

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Author notes

  1. López-González and González-García both contributed equally to this study and must be considered first authors.

Authors and Affiliations

  1. Departamento de Fisiología Humana, Histología Humana, Anatomía Patológica y Educación Física y Deportiva, Facultad de Medicina, Universidad de Málaga, Málaga, Spain

    Manuel Víctor López-González, Marta González-García, Carlos Antonio Peinado-Aragonés, Miguel Ángel Barbancho, Amelia Díaz-Casares & Marc Stefan Dawid-Milner

  2. Unidad de Neurofisiología del Sistema Nervioso Autónomo (CIMES), Universidad de Málaga, Málaga, Spain

    Manuel Víctor López-González, Marta González-García, Amelia Díaz-Casares & Marc Stefan Dawid-Milner

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  1. Manuel Víctor López-González
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  2. Marta González-García
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  3. Carlos Antonio Peinado-Aragonés
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  4. Miguel Ángel Barbancho
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  5. Amelia Díaz-Casares
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  6. Marc Stefan Dawid-Milner
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Correspondence to Manuel Víctor López-González.

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Ethical approval

All experimental protocols were performed in accordance with the recommendations of the European Union directive (2010/63/EU) for animal care and experimental procedures. The experiments were approved by the Ethical Committee for Animal Research of the University of Malaga and the Junta de Andalucía. Every attempt was made to reduce animal suffering, discomfort and the number of animals needed to obtain reliable results.

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Key points

- A5 region inhibition reduces dlPAG evoked tachycardic and tachypnoeic responses.

- Some A5 cells recorded were affected by dlPAG stimulation.

- A5 region and dlPAG are shown to be functionally related.

Díaz-Casares and Dawid-Milner both had equally responsibility and must be considered last authors.

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López-González, M.V., González-García, M., Peinado-Aragonés, C.A. et al. Pontine A5 region modulation of the cardiorespiratory response evoked from the midbrain dorsolateral periaqueductal grey. J Physiol Biochem 76, 561–572 (2020). https://doi.org/10.1007/s13105-020-00761-1

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