Respiratory calcium fluctuations in low-frequency oscillating astrocytes in the pre-Bötzinger complex.
Astrocytes have been found to modulate neuronal activity through calcium-dependent signaling in various brain regions. However, whether astrocytes of the pre-Bötzinger complex (preBötC) exhibit respiratory rhythmic fluctuations is still controversial. Here we evaluated calcium-imaging experiments within preBötC in rhythmically active medullary slices from TgN(hGFAP-EGFP) mice using advanced analyses. 13.8% of EGFP-negative cells, putative neurons, showed rhythmic fluorescent changes that were highly correlated to the respiratory rhythmic fluctuation (cross-correlation coefficient>0.5 and dF/F>0.2%). In contrast, a considerable number of astrocyte somata exhibited synchronized low-frequency (<0.03Hz) calcium oscillations. After band-pass filtering, signals that irregularly preceded the calcium signal of EGFP-negative cells were observed in 10.2% of astrocytes, indicating a functional coupling between astrocytes and neurons in preBötC. A model simulation confirmed that such preinspiratory astrocytic signals can arise from coupled neuronal and astrocytic oscillators, supporting a concept that slow oscillatory changes of astrocytic functions modulate neighboring neuronal activity to add variability in respiratory rhythm.
Department of Physiology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: yoku@hyo-med.ac.jp.
Yoshitaka
Y
Oku
Clinic for Anesthesiology, Laboratory for Experimental Neuroanesthesiology, University Hospital Göttingen, 37099 Göttingen, Germany.
Jens
J
Fresemann
Department of Statistical Modeling, The Institute of Statistical Mathematics, Tokyo 190-8562, Japan; Department of Statistical Science, School of Multidisciplinary Sciences, The Graduate University for Advanced Studies, Tokyo 190-8562, Japan.
Fumikazu
F
Miwakeichi
Clinic for Anesthesiology, Laboratory for Experimental Neuroanesthesiology, University Hospital Göttingen, 37099 Göttingen, Germany; DFG Research Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany. Electronic address: shuelsm2@uni-goettingen.de.
Swen
S
Hülsmann
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D003198:Computer Simulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008526:Medulla Oblongata / Q000166:cytology / Q000378:metabolism*; D008822:Mice, Transgenic; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D012119:Respiration; D046509:Tissue Culture Techniques
D005904:Glial Fibrillary Acidic Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D002118:Calcium
Calcium imaging; Coupled oscillators; Neuron astrocyte interaction; PreBötzinger complex; Respiratory rhythm generation