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Role of Astrocytes in Central Respiratory Chemoreception

  • Jaime Eugenín LeónEmail author
  • María José Olivares
  • Sebastián Beltrán-Castillo
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 949)

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 CO2/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 CO2/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.

Keywords

Respiratory rhythm Central chemoreception Raphe nuclei Locus coeruleus nuclei Retrotrapezoid nuclei Brainstem Glia Gliotransmitters Astrocytes 

Abbreviations

5-HT

5-hydroxytryptamine (Serotonin)

ACh

Acetylcholine

aCSF

Artificial cerebrospinal fluid

AMPAR

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

ANP

Atrial natriuretic peptide

ATP

Adenosine triphosphate

CA

Carbonic anhydrase enzyme

CCHS

Central congenital hypoventilation syndrome

CNS

Central nervous system

CNO

Clozapine-N-oxide

CO2

Carbon dioxide

CNQX

6-cyano-7-nitroquinoxaline-2,3-dione—competitive AMPA/kainate receptor antagonist

cNTS

Caudal nucleus tractus solitarius

CSF

Cerebrospinal fluid

cVLM

Caudal ventrolateral medulla

cVRG

Caudal ventral respiratory group

Cx

Connexins

DRC

Dorsal respiratory columns

EPSP

Excitatory postsynaptic potentials

GABA

γ-aminobutyric acid

GFAP

Glial fibrillary acidic protein

KF

Pontine Kölliker-Fuse nucleus

KO

Knock out

LC

Locus coeruleus

LDT

Laterodorsal tegmental nucleus

LPBR

Lateral parabrachial nucleus

LTP

Long-term potentiation

mRVLM

Medial portion of the rostral ventrolateral medulla

MS

Methionine sulfoximine

NK1R

Neurokinin 1 receptor

NMDA

N-methyl-D-aspartate

NMDAR

N-methyl-D-aspartate receptor

NO

Nitric oxide

NTS

Nucleus tractus solitarius

PaCO2

Partial arterial pressure of carbon dioxide

PCO2

Partial pressure of carbon dioxide

PaO2

Partial arterial pressure of oxygen

PF-LHA

Perifornical-lateral hypothalamic area

PNS

Peripheral nervous system

PPADS

Pyridoxal-phosphate-6-azophenyl-2=,4=-disulfonate

PPT

Pedunculopontine tegmental nucleus

preBötC

PreBötzinger Complex

ORX

Orexin

ORX-KO

Prepro-orexin knockout mice

RN

Medullary raphe nucleus

RPG

Respiratory pattern generator

RTN/pFRG

Retrotrapezoid/parafacial respiratory group

RVL

Nucleus reticularis rostroventrolateralis

RVLM

Rostral ventrolateral medulla

rVRG

Rostral ventral respiratory group

SERT

Serotonin transporter

SIDS

Sudden infant death syndrome

SP

Substance P

SSP-SAP

Saporin–substance P conjugate

TH

Tyrosine hydroxylase

TIRF

Total internal reflection fluorescence

TRH

Thyrotropin releasing hormone

TRP

Channels Transient receptor potential channels

TS-eEPSCs

Tractus solitaries-evoked excitatory postsynaptic currents

VLM

Ventrolateral medullary surface

VMS

Ventral medullary surface

VRC

Ventral respiratory columns

VRG

Ventral respiratory group

Notes

Acknowledgments

Support from Grants Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) #1130874 (JE), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21140669 (MJ Olivares), Comisión Nacional de Ciencia y Tecnología (CONICYT) #21120594 (S Beltrán-Castillo). DICYT-USACH (JE).

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jaime Eugenín León
    • 1
    Email author
  • María José Olivares
    • 1
  • Sebastián Beltrán-Castillo
    • 1
  1. 1.Departamento de BiologíaUniversidad de Santiago de Chile (USACH)SantiagoChile

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