Sympathetic ganglia convey commands that implement reactions to bodily stress. The long-term goals of this project are to understand how three slow synaptic potentials contribute to the normal integrative function of bullfrog sympathetic ganglia and to identify factors that regulate the expression of muscarinic synapses in ganglia. The working hypotheses for this proposal are that 1) ganglia contain physiologically specialized and antomically separate functional channels that modulate different classes of peripheral end organs, 2) slow potentials enable ganglion cells to generate characteristic patterns of activity to drive optimally their specific targets and 3) the synaptic connections of ganglion cells regulate their expression of muscarinic synapses. Isolated preparations containing the ninth and tenth paravertebral ganglia will be used to study the muscarinic excitatory postsynaptic potential (epsp), the muscarinic inhibitory post synaptic potential (ipsp) and a peptidergic epsp mediated by leuteinizing hormone releasing hormone (LHRH). Three physiologically identifiable types of neurons (fast B, slow B, C) within these ganglia innvervate viscera in the lower abdomen (e.g. bladder) and other targets in the hindlimbs (e.g. exocrine glands, vasculature, sensory receptor). However, the relation between these cell types and the hypothesized functional channels is uncertain. A combination of electrophysiological and anatomical methods will be used to provide a detailed description of ganglionic synapses, the morphology of identified sympathetic neurons and the projections of identified cells into cutaneous, motor and visceral branches or peripheral nerves. Next, reports that muscarinic epsps are variable in their voltage-sensitivity will be pursued to determine how heterogeneity in muscarinic excitation is related to the subclasses of B cells and how muscarinic epsps differ in their effects upon repetitive firing. Then muscarinic inhibition of repetitive firing will be analyzed by voltage clamping C cells. After the full range of muscarinic modulation of repetitive firing has been characterized, the influence of specific connections between the ganglia, cord and periphery upon the differential expression of muscarinic responses in ganglion cell types will be studied during axotomy, denervation and re-innervation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021065-03
Application #
3401844
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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

Showing the most recent 10 out of 30 publications