Abstract

The overall objective of the proposed research is to investigate the mechanisms of synaptic plasticity (i.e. modifiability) in the nucleus tractus solitarius (NTS), a brainstem region that serves as the first relay station for many cardiopulmonary afferent inputs. Previous studies using animal models in vivo revealed various memory-like behaviors in respiratory control. The recent discovery of several forms of synaptic plasticity in NTS neurons in vitro provided a possible cellular correlate for such respiratory memory. With the use of an in vitro brainstem slice preparation and whole cell recording and field potential recording techniques for studying synaptic transmission in primary afferent pathways, the present project seeks to discern and characterize the family of synaptic plasticity expressed in the NTS and to elucidate the corresponding cellular mechanisms of their expression. Of particular interest are the conditions for the induction of various forms of long- term, short-term and phasic plasticity as well as the possible cellular mechanisms underlying their expression, including various excitatory and inhibitory amino acid receptors, serotonin receptors and intracellular calcium signaling.
Five specific aims are proposed to investigate these mechanisms. The results obtained will provide valuable insights into the mechanisms of afferent signal integration in the NTS and the corresponding effects on respiratory control.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL060064-01A1
Application #
2764052
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1998-12-07
Project End
2002-11-30
Budget Start
1998-12-07
Budget End
1999-11-30
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Biomedical Engineering
Type
Schools of Arts and Sciences
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
02139

  Publications

Bantikyan, Armenak; Song, Gang; Feinberg-Zadek, Paula et al. (2009) Intrinsic and synaptic long-term depression of NTS relay of nociceptin- and capsaicin-sensitive cardiopulmonary afferents hyperactivity. Pflugers Arch 457:1147-59
Rachmuth, Guy; Poon, Chi-Sang (2004) In-silico model of NMDA and non-NMDA receptor activities using analog very-large-scale integrated circuits. Adv Exp Med Biol 551:171-5
Poon, Chi-Sang (2004) Organization of central pathways mediating the Hering-Breuer reflex and carotid chemoreflex. Adv Exp Med Biol 551:95-100
Song, Gang; Poon, Chi-Sang (2004) Functional and structural models of pontine modulation of mechanoreceptor and chemoreceptor reflexes. Respir Physiol Neurobiol 143:281-92
Young, Daniel L; Eldridge, Frederick L; Poon, Chi-Sang (2003) Integration-differentiation and gating of carotid afferent traffic that shapes the respiratory pattern. J Appl Physiol 94:1213-29
Fan, G; Beard, C; Chen, R Z et al. (2001) DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals. J Neurosci 21:788-97
Young, D L; Siniaia, M S; Poon, C S (2001) NMDA receptor blockade unmasks novel gating and memory mechanisms in vagal control of respiratory rhythm. Adv Exp Med Biol 499:261-6
Young, D L; Siniaia, M S; Poon, C S (2001) Model of nonassociative learning in vagal-pontine modulation of the respiratory rhythm. Adv Exp Med Biol 499:255-60
Poon, C S; Siniaia, M S (2000) Plasticity of cardiorespiratory neural processing: classification and computational functions. Respir Physiol 122:83-109
Poon, C S; Zhou, Z; Champagnat, J (2000) NMDA receptor activity in utero averts respiratory depression and anomalous long-term depression in newborn mice. J Neurosci 20:RC73

Showing the most recent 10 out of 14 publications