application): The long-term goal of the research is to define the physiological significance of the rapid rhythmic components (cardiac-related and 10-Hz) in sympathetic nerve discharge (SND). Work from the principal investigator's (PI's) laboratory indicates that these rhythms arise from different systems of coupled neural oscillators in the brain stem. Each of the oscillators in each system preferentially or selectively controls a different portion of the spinal sympathetic outflow and thus a different cardiovascular target. The central hypothesis is that these rhythms reflect the ability of the brain to coordinate the discharges of sympathetic nerves to different targets. The specific hypotheses to be tested are 1) Highly differentiated patterns of spinal sympathetic outflow and the resulting cardiovascular responses, such as that occurring during the defense reaction, are emergent properties of the systems of coupled brainstem oscillators responsible for the 10-Hz and cardiac-related rhythms in SND. 2) Single brainstem neurons with activity correlated to the 10 Hz and/or cardiac-related rhythms in SND can be distinguished on the basis of the postganglionic nerves that they control. 3) Nonlinear frequency-locking of the generators of the cardiac-related and 10 Hz rhythms is an important mechanism for regulating the balance between those two components of SND and thus the pattern of spinal sympathetic outflow. 4) A newly-discovered 4 Hz noncardiac-related rhythm in SND is generated by forebrain circuits that control cardiovascular function. 5) Functionally distinct subsets of preganglionic neurons are linked by intraspinal connections. This would allow highly differentiated patterns of spinal sympathetic outflow generated in the brainstem to be reinforced or fine-tuned by use of these intraspinal connections. Experiments will be performed in vivo on urethane-anesthetized cats. Extracellular recordings of brainstem unit activity and local field potentials will be made concurrently with recordings of the discharges of postganglionic sympathetic nerves with diverse cardiovascular targets. The above listed hypotheses will be tested by examining the interrelations of these signals using computational methods including spike-triggered averaging, phase plane, ordinary and partial coherence and bicoherence analyses.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL013187-32
Application #
6329997
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Velletri, Paul A
Project Start
1978-12-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2001-11-30
Support Year
32
Fiscal Year
2001
Total Cost
$250,487
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
Gebber, Gerard L; Das, Mahasweta; Barman, Susan M (2004) An unusual form of phase walk in a system of coupled oscillators. J Biol Rhythms 19:542-50
Fadel, Paul J; Orer, Hakan S; Barman, Susan M et al. (2004) Fractal properties of human muscle sympathetic nerve activity. Am J Physiol Heart Circ Physiol 286:H1076-87
Das, Mahasweta; Gebber, Gerard L; Barman, Susan M et al. (2003) Fractal properties of sympathetic nerve discharge. J Neurophysiol 89:833-40
Orer, Hakan S; Das, Mahasweta; Barman, Susan M et al. (2003) Fractal activity generated independently by medullary sympathetic premotor and preganglionic sympathetic neurons. J Neurophysiol 90:47-54
Zhou, Shi-Yi; Gebber, Gerard L; Zhong, Sheng et al. (2002) Pathways involved in synchronization of sympathetic nerve discharge to lung inflation. Brain Res 931:107-16
Gebber, G L (2001) A defence-like reaction: an emergent property of a system of coupled non-linear oscillators. Clin Exp Pharmacol Physiol 28:125-9
Larsen, P D; Zhong, S; Gebber, G L et al. (2001) Sympathetic nerve and cardiovascular responses to chemical activation of the midbrain defense region. Am J Physiol Regul Integr Comp Physiol 280:R1704-12
Lewis, C D; Gebber, G L; Larsen, P D et al. (2001) Long-term correlations in the spike trains of medullary sympathetic neurons. J Neurophysiol 85:1614-22
Larsen, P D; Lewis, C D; Gebber, G L et al. (2000) Partial spectral analysis of cardiac-related sympathetic nerve discharge. J Neurophysiol 84:1168-79
Larsen, P D; Zhong, S; Gebber, G L et al. (2000) Differential pattern of spinal sympathetic outflow in response to stimulation of the caudal medullary raphe. Am J Physiol Regul Integr Comp Physiol 279:R210-21

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