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*, Alexander V. Gourine

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

91 Citations (Scopus)
430 Downloads (Pure)

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.
Original languageEnglish
Article number370
Number of pages10
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 25 Jan 2018

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