This project will explore a new paradigm for neural control of breathing which suggests an important role for learning and memory in the central integration of respiratory-related afferent inputs and resultant optimization of respiratory output. The proposed research is motivated by three major recent discoveries: a) in-vitro studies which revealed certain forms of synaptic plasticity in brainstem respiratory-related regions; b) in-vivo studies which demonstrated corresponding forms of nonassociative learning in respiratory pattern generation; and c) modeling studies which suggested learning and memory as useful neural strategies in the optimal regulation of respiratory pattern. The primary objective of the proposed investigation is to obtain direct electrophysiological and pharmacological evidence of learning and memory in specific brainstem nuclei that would bridge the gap between the in-vitro, in-vivo and modeling data as well as elucidate the functional significance of such neural strategies.
The specific aims are to discern the following forms of learning and memory in vivo: 1) plasticity of vagal """"""""pump cells"""""""" in the nucleus tractus solitarius (NTS); 2) plasticity of carotid chemoafferent input to NTS cells; 3) plasticity in pontine respiratory-related regions. The unit recordings of evoked neuronal activities in these brainstem regions will be compared with corresponding adaptations in the vagal Hering-Breuer reflex and carotid chemoreflex before and after various pharmacological interventions and brainstem lesions in vivo. The results will shed light on the mechanisms of adaptive neural control of breathing in healthy states as well as the neural strategies toward the minimization of the risks of apnea and apneusis in various acute or chronic obstructive and restrictive lung diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL067966-04
Application #
6880053
Study Section
Special Emphasis Panel (ZRG1-RESP (04))
Program Officer
Twery, Michael
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$372,375
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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

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