Sympathetic ganglia convey signals that mediate adaptive responses to stress. The long-term goals of this project are to understand two fundamental aspects of normal sympathetic physiology. The first goal is to identify functional subsystems of sympathetic neurons that innervate selectively different classes of peripheral targets (eg. blood vessels vs. glands) and the second goal is to determine the integrative role of slow synaptic transmission in sympathetic ganglia. The underlying hypotheses are that functional subclasses of sympathetic neurons release different combinations of co-transmitters to control their respective targets and that slow synaptic potentials in ganglia serve to modulate the firing of repetitive action potentials thereby providing a mechanism for regulating the release of individual co-transmitters from a given class of ganglion cells. The most important aspect of this project is to provide a model for understanding the physiological significance of muscarinic and peptidergic synapses in autonomic ganglia. In addition, this research will develop an in vitro system for identifying cellular and molecular mechanisms that regulate phenotypic properties of functionally distinct sympathetic neurons. Using bullfrogs, a combination of electrophysiological and anatomical methods will be used to address four specific aims: 1) Test the hypothesis that sympathetic C cells are vasomotor neurons that utilize epinephrine (EPI), neuropeptide Y (NPY) and adenosine triphosphate (ATP) as co-transmitters. 2) Determine how muscarinic and peptidergic synaptic potentials in ganglia and the repetitive firing that they engender, each regulate the release of EPI, NPY and ATP from C neurons onto arteries. 3) Develop a tissue culture system in which a vasomotor C cells can be identified and the use patch clamp methods to characterize the membrane currents that produce and modulate the repetitive firing of action potentials. 4) Test the hypothesis that fast B and/or slow B but not C-type sympathetic neurons innervate cutaneous mucous glands and granular glands. Then find suitable anatomical markers that can be used to trace the peripheral projections of B-type neurons and to identify dissociated B neurons in tissue culture

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Neurological Sciences Subcommittee 1 (NLS)
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University of Pittsburgh
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Springer, Mitchell G; Kullmann, Paul H M; Horn, John P (2015) Virtual leak channels modulate firing dynamics and synaptic integration in rat sympathetic neurons: implications for ganglionic transmission in vivo. J Physiol 593:803-23
Rimmer, Katrina; Horn, John P (2010) Weak and straddling secondary nicotinic synapses can drive firing in rat sympathetic neurons and thereby contribute to ganglionic amplification. Front Neurol 1:130
Kullmann, Paul H M; Horn, John P (2010) Homeostatic regulation of M-current modulates synaptic integration in secretomotor, but not vasomotor, sympathetic neurons in the bullfrog. J Physiol 588:923-38
Kullmann, Paul H M; Horn, John P (2010) Vasomotor sympathetic neurons are more excitable than secretomotor sympathetic neurons in bullfrog paravertebral ganglia. Auton Neurosci 155:19-24
Li, Chen; Horn, John P (2008) Differential Inhibition of Ca2+ channels by alpha2-adrenoceptors in three functional subclasses of rat sympathetic neurons. J Neurophysiol 100:3055-63
Horn, J P; Kullmann, P H M (2007) Dynamic Clamp Analysis of Synaptic Integration in Sympathetic Ganglia. Neirofiziologiia 39:423-429
Headley, Drew B; Suhan, Nadine M; Horn, John P (2007) Different subcellular distributions of the vesicular monoamine transporter, VMAT2, in subclasses of sympathetic neurons. Brain Res 1129:156-60
Li, Chen; Horn, John P (2006) Physiological classification of sympathetic neurons in the rat superior cervical ganglion. J Neurophysiol 95:187-95
Kullmann, Paul H M; Horn, John P (2006) Excitatory muscarinic modulation strengthens virtual nicotinic synapses on sympathetic neurons and thereby enhances synaptic gain. J Neurophysiol 96:3104-13
Headley, Drew B; Suhan, Nadine M; Horn, John P (2005) Rostro-caudal variations in neuronal size reflect the topography of cellular phenotypes in the rat superior cervical sympathetic ganglion. Brain Res 1057:98-104

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