Astrocytes release prostaglandin E2 to modify respiratory network activity

Elife. 2017 Oct 6:6:e29566. doi: 10.7554/eLife.29566.

Abstract

Previously (Forsberg et al., 2016), we revealed that prostaglandin E2 (PGE2), released during hypercapnic challenge, increases calcium oscillations in the chemosensitive parafacial respiratory group (pFRG/RTN). Here, we demonstrate that pFRG/RTN astrocytes are the PGE2 source. Two distinct astrocyte subtypes were found using transgenic mice expressing GFP and MrgA1 receptors in astrocytes. Although most astrocytes appeared dormant during time-lapse calcium imaging, a subgroup displayed persistent, rhythmic oscillating calcium activity. These active astrocytes formed a subnetwork within the respiratory network distinct from the neuronal network. Activation of exogenous MrgA1Rs expressed in astrocytes tripled astrocytic calcium oscillation frequency in both the preBötzinger complex and pFRG/RTN. However, neurons in the preBötC were unaffected, whereas neuronal calcium oscillatory frequency in pFRG/RTN doubled. Notably, astrocyte activation in pFRG/RTN triggered local PGE2 release and blunted the hypercapnic response. Thus, astrocytes play an active role in respiratory rhythm modulation, modifying respiratory-related behavior through PGE2 release in the pFRG/RTN.

Keywords: astrocytes; brainstem; chemosensitivity; mouse; neural network; neuroscience; prostaglandins; respiration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Calcium Signaling*
  • Dinoprostone / metabolism*
  • Mice, Transgenic
  • Optical Imaging
  • Respiratory Center / drug effects*
  • Respiratory Center / physiology*

Substances

  • Dinoprostone

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.