The objective of this grant is to analyze the neural pathways involved in central regulation of the cardiovascular system. Using neuroanatomical transport techniques, we wish to study the efferent connections of specific subnuclei of the nucleus tractus solitarius. The efferent connections of the rostral, intermediate, and caudal regions of the ventral medulla oblongata will be studied with both anterograde and retrograde transport techniques. In some experiments, these will be combined with immunohistochemical methods. The role of substance P in central control of blood pressure will be examined. The descending ventral medulla substance P pathway which appears to regulate the sympathetic outflow will be examined. The objective will be to determine if substance P is synthesized and transported from the ventral medulla to the intermediolateral cell column. The presence of substance P receptors on sympathetic preganglionic neuron will be studied in normal and spontaneously hypertensive rats. Inhibitors of substance P will be used to determine potential differences in blood pressure regulation in hypertensive and normotensive rats. Finally, the regional vascular flow patterns and cardiac output will be examined after chemical excitation of the ventral medulla in normal, sympathectomized, and midbrain transected rats.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Washington University
Schools of Medicine
Saint Louis
United States
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Miller, Rebecca L; Denny, George O; Knuepfer, Mark M et al. (2015) Blockade of ENaCs by amiloride induces c-Fos activation of the area postrema. Brain Res 1601:40-51
Miller, Rebecca L; Loewy, Arthur D (2014) 5-HT neurons of the area postrema become c-Fos-activated after increases in plasma sodium levels and transmit interoceptive information to the nucleus accumbens. Am J Physiol Regul Integr Comp Physiol 306:R663-73
Miller, Rebecca L; Wang, Michelle H; Gray, Paul A et al. (2013) ENaC-expressing neurons in the sensory circumventricular organs become c-Fos activated following systemic sodium changes. Am J Physiol Regul Integr Comp Physiol 305:R1141-52
Miller, Rebecca L; Loewy, Arthur D (2013) ENaC ýý-expressing astrocytes in the circumventricular organs, white matter, and ventral medullary surface: sites for Na+ regulation by glial cells. J Chem Neuroanat 53:72-80
Miller, R L; Knuepfer, M M; Wang, M H et al. (2012) Fos-activation of FoxP2 and Lmx1b neurons in the parabrachial nucleus evoked by hypotension and hypertension in conscious rats. Neuroscience 218:110-25
Shin, Jung-Won; Geerling, Joel C; Stein, Matthew K et al. (2011) FoxP2 brainstem neurons project to sodium appetite regulatory sites. J Chem Neuroanat 42:1-23
Geerling, Joel C; Stein, Matthew K; Miller, Rebecca L et al. (2011) FoxP2 expression defines dorsolateral pontine neurons activated by sodium deprivation. Brain Res 1375:19-27
Miller, R L; Stein, M K; Loewy, A D (2011) Serotonergic inputs to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei that project to the ventral tegmental area. Neuroscience 193:229-40
Geerling, Joel C; Shin, Jung-Won; Chimenti, Peter C et al. (2010) Paraventricular hypothalamic nucleus: axonal projections to the brainstem. J Comp Neurol 518:1460-99
Stein, Matthew K; Loewy, Arthur D (2010) Area postrema projects to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei: brainstem sites implicated in sodium appetite regulation. Brain Res 1359:116-27

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