Core respiratory network organization: Insights from optogenetics and modeling (Ausborn et al 2018)

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Accession:266687
"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."
Reference:
1 . Ausborn J, Koizumi H, Barnett WH, John TT, Zhang R, Molkov YI, Smith JC, Rybak IA (2018) Organization of the core respiratory network: Insights from optogenetic and modeling studies. PLoS Comput Biol 14:e1006148 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Brainstem;
Cell Type(s): PreBotzinger complex neuron;
Channel(s): Channelrhodopsin (ChR);
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: MATLAB;
Model Concept(s): Oscillations; Activity Patterns;
Implementer(s): Ausborn, Jessica [jessica.ausborn at gmail.com]; Rybak,Ilya A [rybak at drexel.edu];
Search NeuronDB for information about:  Channelrhodopsin (ChR);
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