Optogenetic excitation of preBötzinger complex neurons potently drives inspiratory activity <i>in vivo</i>
Bibliographic record
Abstract
KEY POINTS: This study investigates the effects on ventilation of an excitatory stimulus delivered in a spatially and temporally precise manner to the inspiratory oscillator, the preBötzinger complex (preBötC). We used an adeno-associated virus expressing channelrhodopsin driven by the synapsin promoter to target the region of the preBötC. Unilateral optogenetic stimulation of preBötC increased respiratory rate, minute ventilation and increased inspiratory modulated genioglossus muscle activity. Unilateral optogenetic stimulation of preBötC consistently entrained respiratory rate up to 180 breaths min(-1) both in presence of ongoing respiratory activity and in absence of inspiratory activity. Unilateral optogenetic stimulation of preBötC induced a strong phase-independent Type 0 respiratory reset, with a short delay in the response of 100 ms. We identified a refractory period of ∼200 ms where unilateral preBötC optogenetic stimulation is not able to initiate the next respiratory event. ABSTRACT: Understanding the sites and mechanisms underlying respiratory rhythmogenesis is of fundamental interest in the field of respiratory neurophysiology. Previous studies demonstrated the necessary and sufficient role of preBötzinger complex (preBötC) in generating inspiratory rhythms in vitro and in vivo. However, the influence of timed activation of the preBötC network in vivo is as yet unknown given the experimental approaches previously used. By unilaterally infecting preBötC neurons using an adeno-associated virus expressing channelrhodopsin we photo-activated the network in order to assess how excitation delivered in a spatially and temporally precise manner to the inspiratory oscillator influences ongoing breathing rhythms and related muscular activity in urethane-anaesthetized rats. We hypothesized that if an excitatory drive is necessary for rhythmogenesis and burst initiation, photo-activation of preBötC not only will increase respiratory rate, but also entrain it over a wide range of frequencies with fast onset, and have little effect on ongoing respiratory rhythm if a stimulus is delivered during inspiration. Stimulation of preBötC neurons consistently increased respiratory rate and entrained respiration up to fourfold baseline conditions. Furthermore, brief pulses of photostimulation delivered at random phases between inspiratory events robustly and consistently induced phase-independent (Type 0) respiratory reset and recruited inspiratory muscle activity at very short delays (∼100 ms). A 200 ms refractory period following inspiration was also identified. These data provide strong evidence for a fine control of inspiratory activity in the preBötC and provide further evidence that the preBötC network constitutes the fundamental oscillator of inspiratory rhythms.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".