SheikhBahaei, Shahriar and Turovsky, EA and Hosford, Patrick and Hadjihambi, Anna and Theparambil, SM and Liu, B and Marina, N and Teschemacher, AG and Kasparov, S and Smith, JC and Gourine, Alexander (2018) Astrocytes modulate brainstem respiratory rhythm-generating circuits and determine exercise capacity. Nature Communications, 9: 370. ISSN 2041-1723
Full text not available from this repository.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.