Role of Astrocytes in Central Respiratory Chemoreception

Abstract

Astrocytes perform various homeostatic functions in the nervous system beyond that of a supportive or metabolic role for neurons. A growing body of evidence indicates that astrocytes are crucial for central respiratory chemoreception. This review presents a classical overview of respiratory central chemoreception and the new evidence for astrocytes as brainstem sensors in the respiratory response to hypercapnia. We review properties of astrocytes for chemosensory function and for modulation of the respiratory network. We propose that astrocytes not only mediate between CO/H levels and motor responses, but they also allow for two emergent functions: (1) Amplifying the responses of intrinsic chemosensitive neurons through feedforward signaling via gliotransmitters and; (2) Recruiting non-intrinsically chemosensitive cells thanks to volume spreading of signals (calcium waves and gliotransmitters) to regions distant from the CO/H sensitive domains. Thus, astrocytes may both increase the intensity of the neuron responses at the chemosensitive sites and recruit of a greater number of respiratory neurons to participate in the response to hypercapnia.

Characterisation of medullary astrocytic populations in respiratory nuclei and alterations in sudden unexpected death in epilepsy

“…Also, dysfunction of serotonergic systems is implicated in SUDEP (Murugesan et al, 2018;Richerson, 2013) and in experimental models, decreased responses of serotonergic neurons of medullary raphe has been shown following seizures (Zhan et al, 2016). We previously found a reduction in tryptophan hydroxylase-expressing neurones in the raphe in SUDEP (Patodia et al, 2018) ; as specialised glia have the functional capacity to amplify intrinsic chemosensitive neuronal responses through gliotransmitters (Eugenin Leon et al, 2016), a paucity in raphe glia could further impair these responses during seizures.…”

Morphometric analysis of astrocytes in brainstem respiratory regions

“…While it has been proposed that astrocytes can modulate the activities of CNS circuits and modulate complex behaviors (Amiri, Bahrami, & Janahmadi, ; Angulo, Kozlov, Charpak, & Audinat, ; Burkeen, Womac, Earnest, & Zoran, ; Fellin et al, ; Haydon, ), evidence for such modulation has only recently emerged (Gourine et al, ; Sheikhbahaei et al, ; Yang, Qi, & Yang, ). In the rodent brainstem, astrocytes have been shown to play a role in chemosensing and modulation of respiratory circuit activity (Angelova et al, ; Ballanyi, Panaitescu, & Ruangkittisakul, ; Eugenín León, Olivares, & Beltrán‐Castillo, ; Funk et al, ; Gomeza et al, ; Gourine et al, ; Grass et al, ; Huckstepp et al, ; Hülsmann, Oku, Zhang, & Richter, ; Kasymov et al, ; Marina et al, ; Mulkey & Wenker, ; Okada et al, ; Rajani, Zhang, Revill, & Funk, ; Sheikhbahaei et al, ; Turovsky et al, ; Turovsky, Karagiannis, Abdala, & Gourine, ), including the rhythm‐generating circuits of the preBötzinger complex (preBötC) located within the ventrolateral medullary reticular formation (Feldman, Del Negro, & Gray, ; Smith, Ellenberger, Ballanyi, Richter, & Feldman, ). Astrocytes are critically important for glutamate re‐cycling.…”

“…emerged (Gourine et al, 2010;Sheikhbahaei et al, 2018;Yang, Qi, & Yang, 2015). In the rodent brainstem, astrocytes have been shown to play a role in chemosensing and modulation of respiratory circuit activity (Angelova et al, 2015;Ballanyi, Panaitescu, & Ruangkittisakul, 2010;Eugenín León, Olivares, & Beltrán-Castillo, 2016;Funk et al, 2015;Gomeza et al, 2003;Gourine et al, 2010;Grass et al, 2004;Huckstepp et al, 2010;Hülsmann, Oku, Zhang, & Richter, 2000;Kasymov et al, 2013;Marina et al, 2018;Mulkey & Wenker, 2011;Okada et al, 2012;Rajani, Zhang, Revill, & Funk, 2016;Sheikhbahaei et al, 2018;Turovsky et al, 2016;Turovsky, Karagiannis, Abdala, & Gourine, 2015), including the rhythm-generating circuits of the preBötzinger complex (preBötC) located within the ventrolateral medullary reticular formation (Feldman, Del Negro, & Gray, 2013;Smith, Ellenberger, Ballanyi, Richter, & Feldman, 1991).…”

Activity-induced Ca2+ signaling in perisynaptic Schwann cells of the early postnatal mouse is mediated by P2Y1 receptors and regulates muscle fatigue

“…The interpretation of these effects is complicated by the observation that the mechanisms contributing to activity-induced Ca 2+ signaling in the fine processes of astrocytes are distinct from those underlying this signal in the cell body ( Bazargani and Attwell, 2016 ). Additionally, the diversity of astrocyte subtypes in the brain ( Eugenín León et al, 2016 ) and of neuronal subtypes associated with individual astrocytes ( Perea and Araque, 2005 ) further challenge the precise identification of activity-induced Ca 2+ responses in these cells. Finally, the extent to which IP 3 R-mediated Ca 2+ signaling reflects all of the effects of activity-induced Gq GPCR activation remain unclear ( Agulhon et al, 2013 ).…”