The purpose of this study is to examine how neurons of propriospinal pathway(s) originating in the C1-C2 region process information from amygdala, subcoeruleus/parabrachial (SC/PB) nuclei, and vagal afferent fibers to modulate sensory-motor integration in the spinal cord. We previously demonstrated that chemical stimulation of C1-C2 neurons modulated spontaneous and visceral-evoked activity in lumbosacral spinal neurons and EMG activity of thoracic paraspinal muscles. Our preliminary data further demonstrate that chemical stimulation of C1 C2 neurons can strongly influence the activity of T3-T4 respiratory-related interneurons. Especially critical to this application are our preliminary results indicating that excitotoxic blockade of C1-C2 neurons with ibotenic acid, attenuated amygdalar and SC/PB modulation of lumbosacral spinal cells. The same lesion reduced vagal effects on lumbosacral neurons and paraspinal muscles. Our results challenge the assumption that descending pathways from supraspinal regions modulate activity of thoracic and lumbosacral neurons through direct projections only. The present application addresses the hypothesis that C1-C2 neurons process information from amygdala, SC/PB and vagal afferents. In turn, C1-C2 neurons strongly influence activity of spinal sensory neurons, thoracic respiration-related interneurons, and somatomotor reflexes. We also hypothesize that amygdala and vagal afferents transmit information to C1-C2 neurons via SC/PB nuclei.
Specific aims are designed to answer the following questions: 1) Are discharge patterns and activities of C1-C2 neurons affected by stimulating specific supraspinal nuclei? 2) Do neurons in C1-C2 segments process information from specific supraspinal nuclei to change sensory and integrative/motor activity in the spinal cord? 3) Do neurons in C1-C2 segments process information from vagal afferents to change integrative/motor and sensory activity in the spinal cord? 4) Do SC/PB nuclei relay information from amygdala and vagal afferent fibers to the C1-C2 segments to change sensory and integrative/motor activity in the spinal cord? Neurophysiological studies to examine extracellular discharge patterns and studies using c-fos as a marker of neuronal activation will be conducted in anesthetized rats.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS035471-05
Application #
6541767
Study Section
Respiratory Physiology Study Section (RESP)
Program Officer
Kleitman, Naomi
Project Start
1996-09-01
Project End
2007-05-31
Budget Start
2002-07-05
Budget End
2003-05-31
Support Year
5
Fiscal Year
2002
Total Cost
$278,350
Indirect Cost
Name
University of Oklahoma Health Sciences Center
Department
Physiology
Type
Schools of Medicine
DUNS #
937727907
City
Oklahoma City
State
OK
Country
United States
Zip Code
73117
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Ghorbani, Marie Louise M; Qin, Chao; Wu, Mingyuan et al. (2011) Characterization of upper thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in diabetic rats. Auton Neurosci 165:168-77
Qin, Chao; Goodman, Melanie D; Little, Janine M et al. (2010) Comparison of activity characteristics of the cuneate nucleus and thoracic spinal neurons receiving noxious cardiac and/or somatic inputs in rats. Brain Res 1346:102-11
Goodman-Keiser, Melanie D; Qin, Chao; Thompson, Ann M et al. (2010) Upper thoracic postsynaptic dorsal column neurons conduct cardiac mechanoreceptive information, but not cardiac chemical nociception in rats. Brain Res 1366:71-84
Gao, Jie; Wu, Mingyuan; Li, Linggen et al. (2010) Effects of spinal cord stimulation with ""standard clinical"" and higher frequencies on peripheral blood flow in rats. Brain Res 1313:53-61
Qin, Chao; Malykhina, Anna P; Thompson, Ann M et al. (2010) Cross-organ sensitization of thoracic spinal neurons receiving noxious cardiac input in rats with gastroesophageal reflux. Am J Physiol Gastrointest Liver Physiol 298:G934-42
Qin, C; Yang, X; Wu, M et al. (2009) Modulation of neuronal activity in dorsal column nuclei by upper cervical spinal cord stimulation in rats. Neuroscience 164:770-6
Qin, Chao; Du, Jian-qing; Tang, Jing-shi et al. (2009) Bradykinin is involved in the mediation of cardiac nociception during ischemia through upper thoracic spinal neurons. Curr Neurovasc Res 6:89-94
Qin, Chao; Ghorbani, Marie L M; Wu, Mingyuan et al. (2009) Characterization of upper thoracic spinal neurons responding to esophageal distension in diabetic rats. Auton Neurosci 145:27-34
Wu, Mingyuan; Linderoth, Bengt; Foreman, Robert D (2008) Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: a review of experimental studies. Auton Neurosci 138:9-23

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