The long range goal of this research is to identify electrophysiologically CNS pathways that control sympathetic nerve discharge (SND) and cardiovascular function. The PI has studied these pathways in barbiturate- anesthetized cats in which SND is synchronized into bursts (slow waves) that are locked to the cardiac cycle via the baroreceptor reflex. After baroreceptor-denervation these sympathetic slow waves occur at frequencies varying mainly between 2 and 6 Hz. Others report that in some unanesthetized-decerebrate (UD), urethane-anesthetized, or conscious cats, a 10-Hz rhythm coexists with this 2- to 6-Hz activity. Recent studies in the PI's laboratory confirm the existence of a 10-Hz rhythm in SND of UD, baroreceptor-denervated cats. Key findings of these studies include the following. 1) 10-Hz activity coheres (correlates) strongly among each of the nerves studied (inferior cardiac, vertebral, and renal nerves). 2) Episodes of 10-Hz activity are often followed by increases in arterial pressure, suggesting that this rhythm regulates vasomotor tone. 3) 10-Hz but not 2- to 6-Hz activity is eliminated by a midline sagittal cut of the medulla (0-6 mm rostral to the obex). This occurs without a change in total power in SND, but blood pressure significantly decreases. This suggests that the pattern (10-Hz vs 2- to 6-Hz) rather than just total power in SND regulates the level of blood pressure. 4) The activity of some raphe neurons is synchronized to 10-Hz slow waves in SND. Although this 10-Hz rhythm was described ~ 25 yr ago, no one has yet established its region of origin, properties of central neurons mediating this rhythm, or pathways that relay this activity to sympathetic nerves. Data available suggest that the 10-Hz rhythm is generated in the brainstem. State-of-the- art electrophysiological techniques (spike-triggered averaging, antidromic mapping, and autospectral, coherence, and phase spectral analyses) will be used to address the following aims in experiments on UD cats: 1) to determine the site of origin of this activity, 2) to identify brainstem neurons whose activity is correlated to this rhythm in SND, 3) to determine interconnections of neurons responsible for the 10-Hz rhythm, 4) to assess the functional significance of this rhythm in regulating cardiovascular function, and 5) to assess the effects of central respiratory drive on the frequency of sympathetic nerve slow waves. These studies will determine if the 2- to 6-Hz and 10-Hz components in SND are generated by different brainstem networks, or if the two patterns reflect different physiological states of the same network. These studies will enhance our understanding of the central circuitry responsible for generating resting SND in the absence of the effects of anesthesia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033266-11
Application #
2217211
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1987-09-30
Project End
1995-08-31
Budget Start
1994-09-30
Budget End
1995-08-31
Support Year
11
Fiscal Year
1994
Total Cost
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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