Theoretical perspectives on central chemosensitivity: CO2/H+-sensitive neurons in the locus coeruleus.

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  • Author(s): Quintero MC;Quintero MC; Putnam RW; Putnam RW; Cordovez JM; Cordovez JM
  • Source:
    PLoS computational biology [PLoS Comput Biol] 2017 Dec 21; Vol. 13 (12), pp. e1005853. Date of Electronic Publication: 2017 Dec 21 (Print Publication: 2017).
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't; Validation Study
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238922 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7358 (Electronic) Linking ISSN: 1553734X NLM ISO Abbreviation: PLoS Comput Biol Subsets: MEDLINE
    • Publication Information:
      Original Publication: San Francisco, CA : Public Library of Science, [2005]-
    • Subject Terms:
      Models, Neurological*; Carbon Dioxide/*metabolism ; Chemoreceptor Cells/*physiology ; Locus Coeruleus/*physiology; Action Potentials ; Animals ; Computational Biology ; Electric Stimulation ; Electrophysiological Phenomena ; Humans ; Hydrogen-Ion Concentration ; Hypercapnia/physiopathology ; Hypocapnia/physiopathology ; Locus Coeruleus/cytology ; Synaptic Transmission
    • Abstract:
      Central chemoreceptors are highly sensitive neurons that respond to changes in pH and CO2 levels. An increase in CO2/H+ typically reflects a rise in the firing rate of these neurons, which stimulates an increase in ventilation. Here, we present an ionic current model that reproduces the basic electrophysiological activity of individual CO2/H+-sensitive neurons from the locus coeruleus (LC). We used this model to explore chemoreceptor discharge patterns in response to electrical and chemical stimuli. The modeled neurons showed both stimulus-evoked activity and spontaneous activity under physiological parameters. Neuronal responses to electrical and chemical stimulation showed specific firing patterns of spike frequency adaptation, postinhibitory rebound, and post-stimulation recovery. Conversely, the response to chemical stimulation alone (based on physiological CO2/H+ changes), in the absence of external depolarizing stimulation, showed no signs of postinhibitory rebound or post-stimulation recovery, and no depolarizing sag. A sensitivity analysis for the firing-rate response to the different stimuli revealed that the contribution of an applied stimulus current exceeded that of the chemical signals. The firing-rate response increased indefinitely with injected depolarizing current, but reached saturation with chemical stimuli. Our computational model reproduced the regular pacemaker-like spiking pattern, action potential shape, and most of the membrane properties that characterize CO2/H+-sensitive neurons from the locus coeruleus. This validates the model and highlights its potential as a tool for studying the cellular mechanisms underlying the altered central chemosensitivity present in a variety of disorders such as sudden infant death syndrome, depression, and anxiety. In addition, the model results suggest that small external electrical signals play a greater role in determining the chemosensitive response to changes in CO2/H+ than previously thought. This highlights the importance of considering electrical synaptic transmission in studies of intrinsic chemosensitivity.
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    • Accession Number:
      142M471B3J (Carbon Dioxide)
    • Publication Date:
      Date Created: 20171222 Date Completed: 20180123 Latest Revision: 20200306
    • Publication Date:
      20221213
    • Accession Number:
      PMC5755939
    • Accession Number:
      10.1371/journal.pcbi.1005853
    • Accession Number:
      29267284