The Research Plan is divided into four tightly inter-linked projects that will test novel hypotheses regarding the central neural circuitry that 1) affects basal sympathetic nerve discharge (SND) and the respiratory rhythm as reflected by phrenic nerve activity (PNA) and 2) mediates changes in SND, blood pressure (BP), and respiration produced by activation of an array of vagal and sympathetic afferents. These projects build on work completed during the current funding period and address problems from a unique perspective by focusing on the often ignored """"""""classic pressor area"""""""" in the medullary lateral tegmental field (LTF). The experiments described in Project #1 are the first to seek to identify the source(s) of excitatory drive to LTFsympathoexcitatory neurons that help set the basal level of SND. These experiments have significant bearing on the mechanism by which the neurogenic support for resting BP is generated. Projects #2 & 3 provide the first comprehensive assessment of mechanisms by which """"""""natural"""""""" activation of different types of visceral receptors (mechanoreceptors, chemosensitive receptors) can alter efferent SND, PNA, and ultimately cardiorespiratory function. The reflexes involve activation of myelinated and unmyelinated fibers from cardiopulmonary, gastrointestinal, and renal receptors, and responses include both excitation and inhibition of SND and/or PNA. These reflexes are thought to contribute to cardiorespiratory changes noted during physiological (e.g., lung inflation, digestion, fluid balance) as well as pathophysiological states (e.g., congestive heart failure, myocardial ischemia, sudden infant death syndrome, and esophageal dysfunction). Project #4 addresses the previously unrecognized role of the LTF in determining central respiratory rate. These studies are expected to show that medullary circuits regulating SND are more complexly organized than depicted in most current reviews and that the LTF plays a hitherto unrecognized role in regulating the respiratory rhythm. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL033266-22
Application #
6916964
Study Section
Special Emphasis Panel (ZRG1-CICS (01))
Program Officer
Velletri, Paul A
Project Start
1987-09-30
Project End
2009-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
22
Fiscal Year
2005
Total Cost
$222,438
Indirect Cost
Name
Michigan State University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Barman, Susan M; Orer, Hakan S (2010) Rostral ventrolateral medullary but not medullary lateral tegmental field neurons mediate sympatho-sympathetic reflexes in cats. Am J Physiol Regul Integr Comp Physiol 299:R1269-78
Barman, Susan M; Gebber, Gerard L (2009) The posterior vermis of the cerebellum selectively inhibits 10-Hz sympathetic nerve discharge in anesthetized cats. Am J Physiol Regul Integr Comp Physiol 297:R210-7
Orer, Hakan S; Gebber, Gerard L; Barman, Susan M (2008) Role of serotonergic input to the ventrolateral medulla in expression of the 10-Hz sympathetic nerve rhythm. Am J Physiol Regul Integr Comp Physiol 294:R1435-44
Barman, Susan M; Kenney, Michael J (2007) Methods of analysis and physiological relevance of rhythms in sympathetic nerve discharge. Clin Exp Pharmacol Physiol 34:350-5
Barman, Susan M; Gebber, Gerard L (2007) Role of ventrolateral medulla in generating the 10-Hz rhythm in sympathetic nerve discharge. Am J Physiol Regul Integr Comp Physiol 293:R223-33
Gebber, Gerard L; Orer, Hakan S; Barman, Susan M (2006) Fractal noises and motions in time series of presympathetic and sympathetic neural activities. J Neurophysiol 95:1176-84
Gebber, Gerard L; Barman, Susan M; Fadel, Paul J (2006) Fractal fluctuations in breath number, period, and amplitude are independently controlled in awake, healthy humans. Conf Proc IEEE Eng Med Biol Soc 1:4615-8
Orer, Hakan S; Gebber, Gerard L; Barman, Susan M (2006) Medullary lateral tegmental field neurons influence the timing and pattern of phrenic nerve activity in cats. J Appl Physiol 101:521-30
Phillips, Shaun W; Gebber, Gerard L; Barman, Susan M (2005) Medullary lateral tegmental field: control of respiratory rate and vagal lung inflation afferent influences on sympathetic nerve discharge. Am J Physiol Regul Integr Comp Physiol 288:R1396-410
Barman, Susan M; Orer, Hakan S; Gebber, Gerard L (2005) Role of medullary excitatory amino acid receptors in mediating the 10-Hz rhythm in sympathetic nerve discharge of cats. Brain Res 1049:249-53

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