The cardiac ganglion of the mudpuppy, Necturus maculosus, is an excellent model system for analysis of synaptic integration within a vertebrate cardiac ganglion. Two neuron types are present: parasympathetic postganglionic neurons and SIF cells. The SIF cells contain a number of neurotransmitters including: catecholamines, 5-HT, a substance P-like peptide and a galanin-like peptide. Further, there is an extensive substance P/GGRP immunoreactive afferent fiber input into the cardiac ganglion which make pericellular complexes around postganglionic neurons and SIF cells. We will establish the mechanism(s) by which the afferent fiber and SIF cell input influence the activity of the postganglionic neurons. The following specific questions will be addressed: a) Determine the function and source of the afferent transmission and on the conductance properties of the postganglionic neurons. Immunocytochemical and tracing studies will be done to establish the central origin (i.e., vagal versus spinal) and the peripheral distribution of the substance P/GGRP-immunoreactive fibers. b) Establish the role of SIf cells in the cardiac ganglion. Sif cells will be stimulated while recording from adjacent postganglionic neurons to test whether SIF cells influence postganglionic neuron activity. We will test whether the SIF cells respond to ACh, substance P and CGRP to establish whether these cells are activated by preganglionic and/or afferent transmitters. The action of other neurotransmitters, present in SIF cells such as 5-HT and dopamine, on the membrane properties of postganglionic neurons and ganglionic transmission will be tested. c) Establish the mechanism(s) by which galanin alters, excitability of the postganglionic neurons. The influence of galanin on membrane currents in isolated postganglionic neurons will be determined using cell attached patch and whole cell voltage clamp techniques. The kinetic properties of the galanin activated potassium conductance will be determined using cell attached patch and whole cell voltage clamp techniques. The kinetic properties of the galanin activated potassium conductance, will be determined from single channel activity. An analysis of galanin induced alteration of calcium and potassium conductances will be performed using whole cell voltage clamp procedures. This project will provide important new information in three areas: a) the mechanism(s) of action of specific neurotransmitters on an identified postsynaptic cell, b) the role(s) of SIF cells in autonomic ganglia, and c) the role of afferent fiber input and type (s) of integration which may occur in vertebrate cardiac ganglia that are important in local reflex control of cardiac function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023978-13
Application #
2891686
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Kitt, Cheryl A
Project Start
1997-09-30
Project End
2001-07-31
Budget Start
1999-08-01
Budget End
2000-07-31
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Vermont & St Agric College
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Braas, K M; Rossignol, T M; Girard, B M et al. (2004) Pituitary adenylate cyclase activating polypeptide (PACAP) decreases neuronal somatostatin immunoreactivity in cultured guinea-pig parasympathetic cardiac ganglia. Neuroscience 126:335-46
Parsons, Rodney L; Barstow, Karen L; Scornik, Fabiana S (2002) Spontaneous miniature hyperpolarizations affect threshold for action potential generation in mudpuppy cardiac neurons. J Neurophysiol 88:1119-27
Calupca, Michelle A; Locknar, Sarah A; Parsons, Rodney L (2002) TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia. J Comp Neurol 450:283-91
Scornik, F S; Merriam, L A; Parsons, R L (2001) Number of K(Ca) channels underlying spontaneous miniature outward currents (SMOCs) in mudpuppy cardiac neurons. J Neurophysiol 85:54-60
Calupca, M A; Locknar, S A; Zhang, L et al. (2001) Distribution of cocaine- and amphetamine-regulated transcript peptide in the guinea pig intrinsic cardiac nervous system and colocalization with neuropeptides or transmitter synthetic enzymes. J Comp Neurol 439:73-86
Calupca, M A; Prior, C; Merriam, L A et al. (2001) Presynaptic function is altered in snake K+-depolarized motor nerve terminals containing compromised mitochondria. J Physiol 532:217-27
May, V; Beaudet, M M; Parsons, R L et al. (2000) PACAP modulates rat sympathetic neuron depolarization through IP3. Ann N Y Acad Sci 921:186-94
Beaudet, M M; Parsons, R L; Braas, K M et al. (2000) Mechanisms mediating pituitary adenylate cyclase-activating polypeptide depolarization of rat sympathetic neurons. J Neurosci 20:7353-61
Calupca, M A; Vizzard, M A; Parsons, R L (2000) Origin of neuronal nitric oxide synthase (NOS)-immunoreactive fibers in guinea pig parasympathetic cardiac ganglia. J Comp Neurol 426:493-504
Parsons, R L; Rossignol, T M; Calupca, M A et al. (2000) PACAP peptides modulate guinea pig cardiac neuron membrane excitability and neuropeptide expression. Ann N Y Acad Sci 921:202-10

Showing the most recent 10 out of 44 publications