Pontomedullary Integration of Respiratory Afferents

Summary

Principal Investigator: Chi Sang Poon
Abstract: 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.
Funding Period: ----------------2001 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi Cytoarchitecture of pneumotaxic integration of respiratory and nonrespiratory information in the rat
    Gang Song
    Harvard University Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
    J Neurosci 26:300-10. 2006
  2. pmc Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading
    Chi Sang Poon
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 186:114-30. 2013
  3. ncbi Iono-neuromorphic implementation of spike-timing-dependent synaptic plasticity
    Yicong Meng
    Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Conf Proc IEEE Eng Med Biol Soc 2011:7274-7. 2011
  4. ncbi Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator
    Chi Sang Poon
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA Electronic address
    Prog Brain Res 209:235-54. 2014
  5. pmc Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis
    Steffen Wittmeier
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 105:18000-5. 2008
  6. pmc Phrenic long-term facilitation is robust to hypercapnia and hypocapnia but not hyperventilatory hypotension under PEEP
    Michelle McGuire
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Bldg 56 046, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 158:107-11. 2007
  7. ncbi Modulation of Hering-Breuer reflex by ventrolateral pons
    Hui Wang
    Shandong University, Laboratory of Respiratory Neurobiology, Institute of Physiology, School of Medicine, Jinan 250012, PR China
    Adv Exp Med Biol 605:387-92. 2008
  8. pmc Homeostasis of exercise hyperpnea and optimal sensorimotor integration: the internal model paradigm
    Chi Sang Poon
    Harvard MIT Division of Health Sciences and Technology, Bldg 56 046, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 159:1-13; discussion 14-20. 2007
  9. pmc Nonassociative learning promotes respiratory entrainment to mechanical ventilation
    Shawna M MacDonald
    Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS ONE 2:e865. 2007
  10. pmc Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity
    Armenak Bantikyan
    Massachusetts Institute of Technology, Cambridge, 02139, USA
    Pflugers Arch 457:1147-59. 2009

Scientific Experts

  • Chi Sang Poon
  • G Song
  • Bo Yu
  • Shawna M MacDonald
  • Chung Tin
  • Guy Rachmuth
  • Yicong Meng
  • Christian Straus
  • Chuang Chung J Lee
  • Armenak Bantikyan
  • Steffen Wittmeier
  • Hui Wang
  • Michelle McGuire
  • Nathalie Bautin
  • Mark F Bear
  • Harel Z Shouval
  • Ziyad Samara
  • Marc Zelter
  • Kuan Zhou
  • Pierre Darré
  • Patrick Le Coz
  • Marie Noelle Fiamma
  • Anja Ranohavimparany
  • Thomas Similowski
  • Joshua J C Monzon
  • Jean Louis Golmard
  • Paula Feinberg-Zadek
  • Mihai Anton
  • Gregory J McRae
  • James Duffin
  • Heng Zhang

Detail Information

Publications22

  1. ncbi Cytoarchitecture of pneumotaxic integration of respiratory and nonrespiratory information in the rat
    Gang Song
    Harvard University Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, Massachusetts 02139, USA
    J Neurosci 26:300-10. 2006
    ....
  2. pmc Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading
    Chi Sang Poon
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 186:114-30. 2013
    ..Skeletal muscle afferents feedback, while important for early-phase exercise cardioventilatory dynamics, appears inconsequential for late-phase exercise hyperpnea...
  3. ncbi Iono-neuromorphic implementation of spike-timing-dependent synaptic plasticity
    Yicong Meng
    Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Conf Proc IEEE Eng Med Biol Soc 2011:7274-7. 2011
    ..We show that the aVLSI synapse model successfully emulates both the STDP and BCM forms of synaptic plasticity as predicted by the biophysical model...
  4. ncbi Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator
    Chi Sang Poon
    Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA Electronic address
    Prog Brain Res 209:235-54. 2014
    ....
  5. pmc Pacemakers handshake synchronization mechanism of mammalian respiratory rhythmogenesis
    Steffen Wittmeier
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 105:18000-5. 2008
    ..Such a pacemakers handshake process with conjugate excitation-inhibition and PIR provides a reinforcing and evolutionarily advantageous fail-safe mechanism for respiratory rhythmogenesis in mammals...
  6. pmc Phrenic long-term facilitation is robust to hypercapnia and hypocapnia but not hyperventilatory hypotension under PEEP
    Michelle McGuire
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Bldg 56 046, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 158:107-11. 2007
    ..The results suggest that LTF, once developed, is highly robust to changes in CO(2) levels and is attenuated only after severe hypotension secondary to excessive hyperventilation under PEEP...
  7. ncbi Modulation of Hering-Breuer reflex by ventrolateral pons
    Hui Wang
    Shandong University, Laboratory of Respiratory Neurobiology, Institute of Physiology, School of Medicine, Jinan 250012, PR China
    Adv Exp Med Biol 605:387-92. 2008
    ..Results suggested that the vl-pons could influence the respiratory rhythm by modulating the strength of HBR via NMDA receptor-mediated neurotransmission...
  8. pmc Homeostasis of exercise hyperpnea and optimal sensorimotor integration: the internal model paradigm
    Chi Sang Poon
    Harvard MIT Division of Health Sciences and Technology, Bldg 56 046, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 159:1-13; discussion 14-20. 2007
    ....
  9. pmc Nonassociative learning promotes respiratory entrainment to mechanical ventilation
    Shawna M MacDonald
    Harvard Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America
    PLoS ONE 2:e865. 2007
    ..We suggest that this potential adverse effect may be averted by two differentiator forms of nonassociative learning (habituation and desensitization) of the Hering-Breuer reflex via pontomedullary pathways...
  10. pmc Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity
    Armenak Bantikyan
    Massachusetts Institute of Technology, Cambridge, 02139, USA
    Pflugers Arch 457:1147-59. 2009
    ....
  11. pmc Stream-based Hebbian eigenfilter for real-time neuronal spike discrimination
    Bo Yu
    Tsinghua National Laboratory for Information Science and Technology, Institute of Microelectronics, Tsinghua University, Beijing 100084, China
    Biomed Eng Online 11:18. 2012
    ..The large size memory will consume large hardware resources and contribute significant power dissipation, which make GHA difficult to be implemented in portable or implantable multi-channel recording micro-systems...
  12. pmc Hypercapnia attenuates inspiratory amplitude and expiratory time responsiveness to hypoxia in vagotomized and vagal-intact rats
    Chung Tin
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 181:79-87. 2012
    ..These observations stand in contrast to previous reports of hyperadditive peripheral-central chemoreceptor interaction...
  13. pmc A biophysically-based neuromorphic model of spike rate- and timing-dependent plasticity
    Guy Rachmuth
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 108:E1266-74. 2011
    ..The versatile Hebbian synapse device is applicable to a variety of neuroprosthesis, brain-machine interface, neurorobotics, neuromimetic computation, machine learning, and neural-inspired adaptive control problems...
  14. pmc Effects of maturation and acidosis on the chaos-like complexity of the neural respiratory output in the isolated brainstem of the tadpole, Rana esculenta
    Christian Straus
    Service Central d explorations fonctionnelles respiratoires, Groupe Hospitalier Pitie Salpetriere, 47 83 boulevard de l Hopital, Paris Cedex 13, France
    Am J Physiol Regul Integr Comp Physiol 300:R1163-74. 2011
    ..According to the ventilatory generators homology theory, this may also be the case in mammals...
  15. pmc Hypoxia-excited neurons in NTS send axonal projections to Kölliker-Fuse/parabrachial complex in dorsolateral pons
    G Song
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Neuroscience 175:145-53. 2011
    ..These pontine-projecting peripheral chemoafferent inputs may play an important role in the modulation of cardiorespiratory regulation by dorsolateral pons...
  16. ncbi Homeostatic competition: evidence of a serotonin-gated spinoparabrachial pathway for respiratory and thermoregulatory interaction
    Chi Sang Poon
    Harvard MIT Division of Health Sciences and Technology, M I T, Cambridge, MA, USA
    Adv Exp Med Biol 669:61-5. 2010
    ....
  17. pmc A kinetic model unifying presynaptic short-term facilitation and depression
    Chuang Chung J Lee
    Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Room 66 372, Cambridge, MA 02139 4307, USA
    J Comput Neurosci 26:459-73. 2009
    ..New experiments are also suggested to control the short-term synaptic signal processing through adjusting the resonance frequency and bandwidth...
  18. pmc Use-dependent learning and memory of the Hering-Breuer inflation reflex in rats
    Shawna M MacDonald
    Massachusetts Institute of Technology, Cambridge, 02139, USA
    Exp Physiol 94:269-78. 2009
    ..The translational implications of these findings are discussed...
  19. pmc Lateral parabrachial nucleus mediates shortening of expiration and increase of inspiratory drive during hypercapnia
    Gang Song
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 165:9-12. 2009
    ..L., Eldridge, F.L., Poon, C.S., 2003. Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern. J. Appl. Physiol. 94, 1213-1229]...
  20. pmc Lateral parabrachial nucleus mediates shortening of expiration during hypoxia
    Gang Song
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 165:1-8. 2009
    ....
  21. pmc Optimal interaction of respiratory and thermal regulation at rest and during exercise: role of a serotonin-gated spinoparabrachial thermoafferent pathway
    Chi Sang Poon
    Harvard MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Bldg E25 250, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Respir Physiol Neurobiol 169:234-42. 2009
    ....