Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity
- University of Melbourne, Australia
- Florey Institute of Neuroscience and Mental Health, Australia
- Institut de Neurobiologie de la Méditerranée, France
Abstract
The preBötzinger Complex (preBötC), a key primary generator of the inspiratory breathing rhythm, contains neurons that project directly to facial nucleus (7n) motoneurons to coordinate orofacial and nasofacial activity. To further understand the identity of 7n-projecting preBötC neurons, we used a combination of optogenetic viral transgenic approaches to demonstrate that selective photoinhibition of these neurons affects mystacial pad activity, with minimal effects on breathing. These effects are altered by the type of anesthetic employed and also between anesthetised and conscious states. The population of 7n-projecting preBötC neurons we transduced consisted of both excitatory and inhibitory neurons that also send collaterals to multiple brainstem nuclei involved with the regulation of autonomic activity. We show that modulation of subgroups of preBötC neurons, based on their axonal projections, is a useful strategy to improve our understanding of the mechanisms that coordinate and integrate breathing with different motor and physiological behaviours. This is of fundamental importance, given that abnormal respiratory modulation of autonomic activity and orofacial behaviours have been associated with the development and progression of diseases.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2, 3, 8, Figures 8 -supplement 1 and 3, and Figure 9
Article and author information
Author details
Shane Doris Cheung
Stuart J McDougall
Funding
Early Career Research - University of Melbourne (503275)
- Mariana R Melo
Early Career Reasearch Transition Grant of Hypertension Australia Ltd (830365)
- Mariana R Melo
Australian Research Council (DP231003058)
- Andrew M Allen
National Health and Medical Research Council (1156727)
- Andrew M Allen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were conducted in accordance with the National Health and Medical Research Council of Australia's "Guidelines to promote the well-being of animals used for scientific purposes: The assessment and alleviation of pain and distress in research animals (2008)" and "Australian code for the care and use of animals for scientific purposes" and were approved by the University of Melbourne Animal Research Ethics and Biosafety Committees (ethics ID#21396).
Copyright
© 2023, Melo et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Selective transduction and photoinhibition of pre-Bötzinger neurons that project to the facial nucleus in rats affect the nasofacial activity
eLife 12:e85398.
https://doi.org/10.7554/eLife.85398
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Background:
Post-stroke epilepsy (PSE) is a critical complication that worsens both prognosis and quality of life in patients with ischemic stroke. An interpretable machine learning model was developed to predict PSE using medical records from four hospitals in Chongqing.
Methods:
Medical records, imaging reports, and laboratory test results from 21,459 ischemic stroke patients were collected and analyzed. Univariable and multivariable statistical analyses identified key predictive factors. The dataset was split into a 70% training set and a 30% testing set. To address the class imbalance, the Synthetic Minority Oversampling Technique combined with Edited Nearest Neighbors was employed. Nine widely used machine learning algorithms were evaluated using relevant prediction metrics, with SHAP (SHapley Additive exPlanations) used to interpret the model and assess the contributions of different features.
Results:
Regression analyses revealed that complications such as hydrocephalus, cerebral hernia, and deep vein thrombosis, as well as specific brain regions (frontal, parietal, and temporal lobes), significantly contributed to PSE. Factors such as age, gender, NIH Stroke Scale (NIHSS) scores, and laboratory results like WBC count and D-dimer levels were associated with increased PSE risk. Tree-based methods like Random Forest, XGBoost, and LightGBM showed strong predictive performance, achieving an AUC of 0.99.
Conclusions:
The model accurately predicts PSE risk, with tree-based models demonstrating superior performance. NIHSS score, WBC count, and D-dimer were identified as the most crucial predictors.
Funding:
The research is funded by Central University basic research young teachers and students research ability promotion sub-projec t(2023CDJYGRH-ZD06), and by Emergency Medicine Chongqing Key Laboratory Talent Innovation and development joint fund project (2024RCCX10).
