The long-term objective of this grant is to analyze the central neural circuits that regulate autonomic functions with an emphasis on the cardiovascular system. Neuroanatomical techniques will be used to identify and chemically characterize specific CNS neural circuits which affect the sympathetic supply to the heart and adrenal gland. Much of the work described here will utilize the viral transneuronal tracing method-a technique which depends upon the use of an attenuated pig herpes virus to produce transneuronal infections that spread within functionally related chains of central neurons. The first project will analyze the descending projections arising from the amygdala-an important brain region thought to be responsible for emotionally triggered cardiovascular changes. The second project deals with the preoptic region and its potential role in sympathetic control. The third project explores the sympathetic control systems represented within the suprachiasmatic hypothalamic nucleus the CNS pacemaker that provides circadian modulation of some sympathetic functions. The fourth project focuses on the descending cell groups. The fifth project investigates the efferent projections of the periaqueductal gray matter in reference to sympathetic control; this area of the brain has been implicated in programming the fight-or-flight response. These studies will be useful for understanding the brain circuits responsible for sustaining and modulating basic life functions, such as blood pressure and cardiac regulation. In addition, they may provide insights into the underlying CNS mechanisms of certain clinical conditions, such as stress-induced cardiovascular changes and essential hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Application #
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Program Officer
Broman, Sarah H
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Washington University
Anatomy/Cell Biology
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
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
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
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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