A spatially dynamic network underlies the generation of inspiratory behaviors

Baertsch, Nathan A.; Severs, Liza J.; Anderson, Tatiana M.; Ramirez, Jan‐Marino

doi:10.1073/pnas.1900523116

Cited by 60 publications

(48 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the refractory period is not absolute as it can be overcome 519 if the stimulus is of sufficient strength (Vann et al, 2018). Using a stimulus procedure 520 consistent with previous reports (Baertsch et al, 2018, Baertsch et al, 2019 and Del Negro, 2015), we found that SP does not change the duration of the refractory 522 period. This finding is consistent with our demonstration that excitatory neurons do not 523…”

Section: In Glutamatergic 513supporting

confidence: 75%

“…493 Furthermore, recent evidence suggests that inspiratory neurons located rostral to 494 the preBӧtC also contribute to the dynamic regulation of breathing frequency (Baertsch 495 et al, 2019). However, under normal conditions, inhibition restrains the rhythm 496 generating ability of these rostral neurons, as recruitment of these neurons is 497 associated with increased excitation during inspiratory bursts, a prolonged refractory 498 phase, and consequently a decreased respiratory frequency (Baertsch et al, 2019). 499…”

Section: Discussion: 431mentioning

confidence: 99%

See 1 more Smart Citation

Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

Baertsch¹,

Ramirez

2019

Preprint

Self Cite

View full text Add to dashboard Cite

23The rhythm generating network for breathing must continuously adjust to 24 changing metabolic and behavioral demands. Here, we examine network-based 25 mechanisms in the mouse preBӧtzinger complex using substance P, a potent excitatory 26 modulator of breathing frequency and stability, as a tool to dissect network properties 27 that underlie dynamic breathing. We find that substance P does not alter the balance of 28 excitation and inhibition during breaths or the duration of the resulting refractory period. 29Instead, mechanisms of recurrent excitation between breaths are enhanced such that 30the rate that excitation percolates through the network is increased. Based on our 31 results, we propose a conceptual framework in which three distinct phases, the 32 inspiratory phase, refractory phase, and percolation phase, can be differentially 33 modulated to influence breathing dynamics and stability. Unravelling mechanisms that 34 support this dynamic control may improve our understanding of nervous system 35 disorders that destabilize breathing, many of which are associated with changes in 36 brainstem neuromodulatory systems.

show abstract

Section: In Glutamatergic 513supporting

confidence: 75%

Section: Discussion: 431mentioning

confidence: 99%

Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

Baertsch¹,

Ramirez

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…3 k,l), we speculate that a decrease in the synaptic efficacy following network synchronization, e.g., due to increased neuronal conductance, contributes to burstlet/burst termination 48 . While not essential to rhythmogenesis, the inhibition originating in the preBötC does regulate the duration of I-bursts, and modulate breathing pattern 5,7,8,25,49 .…”

Section: Main Textmentioning

confidence: 99%

“…2g1-i, S2d1-e). Given that the excitation-inhibition balance in a network is a critical determinant of its output 24 , including for breathing 5,8,25,26 , we hypothesize that that net impact of increased [K + ] ACSF is to shift the excitation-inhibition balance towards higher excitation, which favors preBötC synchronization. To test this hypothesis, we disinhibited the network by antagonizing gamma-aminobutyric acid type A (GABA A ) or glycinergic receptors.…”

Section: Main Textmentioning

confidence: 99%

Network synchronization and synchrony propagation: emergent elements of inspiration

Ashhad

Feldman

2019

Preprint

View full text Add to dashboard Cite

While now well established that the preBötzinger Complex (preBötC) 1 is the kernel of breathing rhythmogenesis in mammals, the underlying mechanisms remain a mystery 2 . Critically, two long-favored hypotheses for rhythmogenesis, i.e., that the rhythm is generated by pacemaker neurons or by simple circuits dependent on inhibition including post-inhibitory rebound, are not supported by experimental tests 2-8 . Here, we explore an alternative (though non-exclusive) hypothesis, that the rhythm is an emergent property of the preBötC microcircuit 2,6,9,10 . We assessed preBötC network dynamics by recording synaptic inputs to preBötC neurons under respiratory rhythmic and non-rhythmic conditions in in vitro slices from neonatal mouse. Our analyses uncover a dynamic reorganization of preBötC network activity correlated with and, we hypothesize, essential to, rhythmicity. In each cycle under rhythmic conditions, an inspiratory burst (I-burst) emerges as (presumptive) preBötC rhythmogenic neurons transition away from aperiodic uncorrelated population spike activity to become increasingly synchronized during preinspiration; this burst activity subsides and the cycle repeats. Strikingly, in a slice in nonrhythmic conditions, antagonizing GABA A receptors can initiate this periodic synchronization and consequent rhythm, while simultaneously inducing a high conductance (HC) state in preBötC nonrhythmogenic output neurons. This co-emergence of input synchrony and HC state in these output neurons unveils a novel network mechanism for generation of the rhythm that emerges in preBötC and that ultimately propagates to inspiratory motoneurons, effecting inspiratory muscle contraction and consequential breathing movements. In the light of divergent projections of preBötC output neurons through mono-and oligo-synaptic connections 11 , synchronized oscillations in inspiratory motoneurons 12,13 and entrainment of limbic neurons by respiratory corollary discharge 14 , we hypothesize that the evolution and propagation of preBötC synchrony plays a critical role in the extraordinary reliability and robustness of networks underlying respiratory motor output as well as in the use of breathing rhythms for binding of activity with and across higher brain regions.

show abstract

“…It has recently been proposed that the post-inspiratory complex (PiCo) in the brainstem functions as a network oscillator to coordinate this phase of breathing with other central respiratory oscillators, and to produce state-dependent modulations as required for metabolic demands or precision motor acts (Anderson, Garcia, Baertsch, Pollak, Bloom, Wei, Rai, & Ramirez, 2016;Baertsch, Severs, Anderson, & Ramirez, 2019). This is different and potentially adjunctive to laryngeal adduction, which has been classically used to define E1 (Bartlett Jr, 1989;Bartlett Jr, Remmers, & Gautier, 1973;Harding, 1984).…”

Section: Yield: a Novel Description Of Diaphragm Activity During Earlmentioning

confidence: 99%

Coordination of airway protective behaviors and swallow: effects of afferent feedback and sex.

Huff¹

View full text Add to dashboard Cite

First and foremost, I would like to thank Dr. Pitts for her mentorship and support over the past four years. What a journey, physically and mentally, we have been on. Dr. Howland, thank you for always being available to give histology advice and overall support. Dr. Mellen, thank you for spending all of your free time teaching me your SSRH preparation and your determination and dedication to stimulate swallow for 3 years! I'd like to thank Dr. Schuschke, Dr. LeBlanc and Dr. Williams for their guidance and encouragement as members of my thesis committee. I would like to thank Mitch, for your friendship, constant support, corny dad jokes and willingness to listen to all my comments. Kim, thank you for your editorial support throughout this process and to Wilbur for always helping me with anything and everything. Thank you Yun for all your efforts in histology. Additionally, I would like to thank my family for their constant support and willingness to listen to anything I had to say, good or bad, at any time of day or night. Mom, thank you for enstilling in me that I can do anything I put my mind to. Dad, thank you for making science and education a priority in my life early on (eventhough it was engineering and not biological science). Amanda, thank you for paving the way through the PhD process and preparing expectations. I cannot go without thanking all of my sweet bestfriends who have given me more love and support in my life than anyone could understand. You all are amazing women placed in my life to help me realize my potential. The pen is mightier than the sword.

show abstract

A spatially dynamic network underlies the generation of inspiratory behaviors

Cited by 60 publications

References 92 publications

Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

Insights into the dynamic control of breathing revealed through cell-type-specific responses to substance P

Network synchronization and synchrony propagation: emergent elements of inspiration

Coordination of airway protective behaviors and swallow: effects of afferent feedback and sex.

Contact Info

Product

Resources

About