Journal article
Organization of the core respiratory network: Insights from optogenetic and modeling studies
PLoS computational biology, v 14(4), pp e1006148-e1006148
Apr 2018
PMID: 29698394
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The circuit organization within the mammalian brainstem respiratory network, specifically within and between the pre-Bötzinger (pre-BötC) and Bötzinger (BötC) complexes, and the roles of these circuits in respiratory pattern generation are continuously debated. We address these issues with a combination of optogenetic experiments and modeling studies. We used transgenic mice expressing channelrhodopsin-2 under the VGAT-promoter to investigate perturbations of respiratory circuit activity by site-specific photostimulation of inhibitory neurons within the pre-BötC or BötC. The stimulation effects were dependent on the intensity and phase of the photostimulation. Specifically: (1) Low intensity (≤ 1.0 mW) pulses delivered to the pre-BötC during inspiration did not terminate activity, whereas stronger stimulations (≥ 2.0 mW) terminated inspiration. (2) When the pre-BötC stimulation ended in or was applied during expiration, rebound activation of inspiration occurred after a fixed latency. (3) Relatively weak sustained stimulation (20 Hz, 0.5-2.0 mW) of pre-BötC inhibitory neurons increased respiratory frequency, while a further increase of stimulus intensity (> 3.0 mW) reduced frequency and finally (≥ 5.0 mW) terminated respiratory oscillations. (4) Single pulses (0.2-5.0 s) applied to the BötC inhibited rhythmic activity for the duration of the stimulation. (5) Sustained stimulation (20 Hz, 0.5-3.0 mW) of the BötC reduced respiratory frequency and finally led to apnea. We have revised our computational model of pre-BötC and BötC microcircuits by incorporating an additional population of post-inspiratory inhibitory neurons in the pre-BötC that interacts with other neurons in the network. This model was able to reproduce the above experimental findings as well as previously published results of optogenetic activation of pre-BötC or BötC neurons obtained by other laboratories. The proposed organization of pre-BötC and BötC circuits leads to testable predictions about their specific roles in respiratory pattern generation and provides important insights into key circuit interactions operating within brainstem respiratory networks.
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Details
- Title
- Organization of the core respiratory network: Insights from optogenetic and modeling studies
- Creators
- Jessica Ausborn - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States of AmericaHidehiko Koizumi - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States of AmericaWilliam H Barnett - Department of Mathematics and Statistics, Georgia State University, Atlanta, United States of AmericaTibin T John - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States of AmericaRuli Zhang - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States of AmericaYaroslav I Molkov - Department of Mathematics and Statistics, Georgia State University, Atlanta, United States of AmericaJeffrey C Smith - Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States of AmericaIlya A Rybak - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, United States of America
- Publication Details
- PLoS computational biology, v 14(4), pp e1006148-e1006148
- Publisher
- Public LIbrary of Science (PLOS); United States
- Grant note
- R01 NS069220 / NIH HHS U42 OD012210 / NIH HHS R01 AT008632 / NCCIH NIH HHS R01 AT008632 / NIH HHS U01 EB021960 / NIBIB NIH HHS U01 EB021960 / NIH HHS R01 NS069220 / NINDS NIH HHS R01 NS090919 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000432169600059
- Scopus ID
- 2-s2.0-85046350763
- Other Identifier
- 991014877996304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemical Research Methods
- Mathematical & Computational Biology