The longterm goal of our research program is to elucidate the complex neural processing of chemical and mechanical respiratory afferent inputs that underlie the control of breathing by brainstem nuclei in health and in cardiopulmonary diseases. In the past project period we have used single-electrode, single-unit recording and central microinjection and lesioning techniques to explore the neuronal structures and functions in the dorsolateral pons pneumotaxic center and the dorsomedullary nucleus tractus solitarius (NTS) which participate importantly in the integration of vagal and chemoreceptor afferent inputs. In the next phase of our research we propose to employ a state-of-the-art multielectrode/multineuronal recording technique in order to characterize these pontomedullary nuclei at the neural networks level. Our experimental approach combines advanced multielectrode/multineuronal recording technology which is miniaturized for application in the rat brainstem, and advanced statistical techniques for ensemble spike train analysis and data mining in order to decipher the connectivity of the recorded neurons. A key question to be addressed in this project is whether central and peripheral chemoreceptor inputs are simply relayed by pontine respiratory neurons to the respiratory controller or are integrated in a specific manner in modulating the ventilatory pattern.
Our specific aims are to identify and characterize the neural correlates of hypoxic-hypercapnic ventilatory interaction in four major pontine nuclei (Aims 1-4): Lateral and medial parabrachial nuclei and K""""""""lliker-Fuse nucleus in the dorsolateral pons and the A5 region in the ventrolateral pons. Our hypothesis is that a subset of pontine respiratory neurons may integrate hypoxic and hypercapnic inputs in modulating respiratory drive and respiratory rhythm, such that the individual neuronal response and the overall phrenic nerve response to a combination of these inputs may be greater (positive interaction) or smaller (negative interaction) than the sum of responses to separate inputs (no interaction). Identification of the neural correlates of hypoxic-hypercapnic ventilatory interaction and resultant modulation of respiratory drive and respiratory rhythm will shed light on the mechanisms of respiratory instability in certain at-risk subject populations, such as congestive heart failure patients and individuals sleeping at high altitude.

Public Health Relevance

Breathing is a vital bodily function that is fundamental to life. Understanding how various brainstem centers integrate afferent information in the control of breathing is of fundamental importance in the clinical management of a variety of life-threatening conditions such as respiratory failure, chronic cardiopulmonary or airway diseases, sleep apnea, or exposure to extreme environments such as high altitude.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Laposky, Aaron D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Institute of Technology
Other Domestic Higher Education
United States
Zip Code
Yang, Liang; Song, Gang; Ning, Yinghui et al. (2016) A latent serotonin-1A receptor-gated spinal afferent pathway inhibiting breathing. Brain Struct Funct 221:4159-4168
Song, Gang; Tin, Chung; Poon, Chi-Sang (2015) Multiscale fingerprinting of neuronal functional connectivity. Brain Struct Funct 220:2967-82
Poon, Chi-Sang; Tin, Chung; Song, Gang (2015) Submissive hypercapnia: Why COPD patients are more prone to CO2 retention than heart failure patients. Respir Physiol Neurobiol 216:86-93
Poon, Chi-Sang; Song, Gang (2015) Type III-IV muscle afferents are not required for steady-state exercise hyperpnea in healthy subjects and patients with COPD or heart failure. Respir Physiol Neurobiol 216:78-85
Poon, Chi-Sang; Song, Gang (2014) Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator. Prog Brain Res 209:235-54
Poon, Chi-Sang; Tin, Chung (2013) Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading. Respir Physiol Neurobiol 186:114-30
Tin, Chung; Song, Gang; Poon, Chi-Sang (2012) Hypercapnia attenuates inspiratory amplitude and expiratory time responsiveness to hypoxia in vagotomized and vagal-intact rats. Respir Physiol Neurobiol 181:79-87
Song, Gang; Wang, Hui; Xu, Hui et al. (2012) Kölliker–Fuse neurons send collateral projections to multiple hypoxia-activated and nonactivated structures in rat brainstem and spinal cord. Brain Struct Funct 217:835-58
Yu, Bo; Mak, Terrence; Li, Xiangyu et al. (2012) Stream-based Hebbian eigenfilter for real-time neuronal spike discrimination. Biomed Eng Online 11:18
Poon, Chi-Sang (2011) Evolving paradigms in H+ control of breathing: from homeostatic regulation to homeostatic competition. Respir Physiol Neurobiol 179:122-6

Showing the most recent 10 out of 31 publications