Astrocytes modulate brainstem respiratory rhythm-generating circuits and determine exercise capacity

Shahriar Sheikhbahaei, Egor A. Turovsky, Patrick S. Hosford, Anna Hadjihambi, Shefeeq M. Theparambil, Beihui Liu, Nephtali Marina, Anja G. Teschemacher, Sergey Kasparov, Jeffrey C. Smith () and Alexander V. Gourine ()
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Shahriar Sheikhbahaei: University College London
Egor A. Turovsky: University College London
Patrick S. Hosford: University College London
Anna Hadjihambi: University College London
Shefeeq M. Theparambil: University College London
Beihui Liu: University of Bristol
Nephtali Marina: University College London
Anja G. Teschemacher: University of Bristol
Sergey Kasparov: University of Bristol
Jeffrey C. Smith: National Institutes of Health (NIH)
Alexander V. Gourine: University College London

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Astrocytes are implicated in modulation of neuronal excitability and synaptic function, but it remains unknown if these glial cells can directly control activities of motor circuits to influence complex behaviors in vivo. This study focused on the vital respiratory rhythm-generating circuits of the preBötzinger complex (preBötC) and determined how compromised function of local astrocytes affects breathing in conscious experimental animals (rats). Vesicular release mechanisms in astrocytes were disrupted by virally driven expression of either the dominant-negative SNARE protein or light chain of tetanus toxin. We show that blockade of vesicular release in preBötC astrocytes reduces the resting breathing rate and frequency of periodic sighs, decreases rhythm variability, impairs respiratory responses to hypoxia and hypercapnia, and dramatically reduces the exercise capacity. These findings indicate that astrocytes modulate the activity of CNS circuits generating the respiratory rhythm, critically contribute to adaptive respiratory responses in conditions of increased metabolic demand and determine the exercise capacity.

Date: 2018
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DOI: 10.1038/s41467-017-02723-6

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