The fundamental goals of this research proposal are to test the hypotheses that: 1) phrenic motor output is enhanced by spinal release of dopamine and consequent activation of D1 receptors in the ventral horn, and 2) chronic cervical deafferentation (cervical dorsal rhizotomy, C3-C5) enhances dopaminergic modulation of phrenic motoneurons. These investigators will provide novel evidence of spinal dopamine-mediated modulation of respiratory motor output. They will also yield insights into dopaminergic mechanisms that may underlie spinal plasticity in respiratory control. The candidate of this application has attained the D.V.M. and M.S. Degrees and advanced training in Veterinary Anesthesiology. This proposal will coincide with achievement of the Ph.D. Degree and will provide a firm foundation for a career as a clinician-scientist capable of an independent research career. Although her past research history is limited, this proposal will develop the scientific techniques and knowledge crucial for becoming an independent scientific investigator. The training environment will be guided toward mentoring the candidate while teaching valuable research techniques necessary to begin an independent research career. The majority of supervision will be provided by Gordon S. Mitchell, an internationally known and respected investigator in the area of neural control of respiration, Professor of Neuroscience, and Professor and Chairman of Comparative Biosciences. The advisory committee will consist of well-respected and highly experienced individuals within the applicant's department, or another institution. The University of Wisconsin provides an outstanding research environment with a large interactive group of scientists interested in respiratory neurobiology. The proposal is designed to provide insights into dopaminergic mechanisms that may underlie spinal plasticity in respiratory control by studying (a) the effect of spinal release of dopamine and subsequent activation of D, receptors in the ventral horn and (b) the effect of chronic cervical deafferentation on enhancement of dopaminergic modulation of phrenic neourons.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZHL1-CSR-Y (M2))
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Rothgeb, Ann E
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University of Wisconsin Madison
Schools of Veterinary Medicine
United States
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Bavis, Ryan W; Johnson, Rebecca A; Ording, Kari M et al. (2006) Respiratory plasticity after perinatal hypercapnia in rats. Respir Physiol Neurobiol 153:78-91
Johnson, Rebecca A; Mitchell, Gordon S (2003) Exercise-induced changes in hippocampal brain-derived neurotrophic factor and neurotrophin-3: effects of rat strain. Brain Res 983:108-14
Johnson, R A; Rhodes, J S; Jeffrey, S L et al. (2003) Hippocampal brain-derived neurotrophic factor but not neurotrophin-3 increases more in mice selected for increased voluntary wheel running. Neuroscience 121:1-7
Johnson, R A; Mitchell, G S (2001) p-Chlorophenylalanine eliminates long-term modulation of the exercise ventilatory response in goats. Respir Physiol 128:161-9
Johnson, R A; Okragly, A J; Haak-Frendscho, M et al. (2000) Cervical dorsal rhizotomy increases brain-derived neurotrophic factor and neurotrophin-3 expression in the ventral spinal cord. J Neurosci 20:RC77