Substance P, an undecapeptide, has been identified by combined immunohistochemical and radioimmunological techniques to be present in nerve fibers and terminals in amphibian, mammalian, and avian autonomic ganglia. The peptide has been shown to depolarize some sympathetic neurons of frog and guinea pig and to modulate the activation of the acetylcholine receptor (AChR) in chromaffin cells and in embryonic chick autonomic neurons. The physiological role of the peptide in ganglionic transmission remains uncertain, however. The long-range objective of this work is to define the precise physiologic effects of substance P and other peptides in the modulation of cholinergic transmission in developing chick autonomic ganglia.
The specific aims of this proposal focus on first, a determination of the effect of substance P on the activation of the cholinergic receptor. This includes a detailed electrophysiological characterization of substance P's inhibition of ACh-induced inward currents in embryonic autonomic neurons in vitro. Second, the pharmacology of the effect will be studied to examine the action of substance P on the dose dependence of ACh's interaction with the AChR as well as to characterize the substance P receptor in detail. Third, studies will be initiated to examine the mechanism of substance P action at the cholinergic receptor using voltage clamp recording for fluctuation analysis of receptor kinetics as well as single channel recording.
The final aims of this proposal will extend the observation of substance P effects on applied ACh to studies of the peptide at cholinergic synapses in vitro and in vivo. The studies that comprise this proposal constitute the groundwork for the first attempt to describe the development, physiology, pharmacology and biophysical mechanism of substance P modulation of cholinergic synapses in autonomic ganglia. Since the function of the peptide is largely undefined, these studies should yield fundamental and important information about the physiology of substance P. Furthermore, since the peptide is present in central as well as peripheral nerve structures, the implications of this study reach far beyond the ganglia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022061-02
Application #
3403974
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Jing, Miao; Zhang, Peng; Wang, Guangfu et al. (2018) A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies. Nat Biotechnol 36:726-737
Záborszky, Laszlo; Gombkoto, Peter; Varsanyi, Peter et al. (2018) Specific Basal Forebrain-Cortical Cholinergic Circuits Coordinate Cognitive Operations. J Neurosci 38:9446-9458
Zhong, Chongbo; Akmentin, Wendy; Du, Chuang et al. (2017) Axonal Type III Nrg1 Controls Glutamate Synapse Formation and GluA2 Trafficking in Hippocampal-Accumbens Connections. eNeuro 4:
Ballinger, Elizabeth C; Ananth, Mala; Talmage, David A et al. (2016) Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline. Neuron 91:1199-1218
Jiang, Li; Kundu, Srikanya; Lederman, James D et al. (2016) Cholinergic Signaling Controls Conditioned Fear Behaviors and Enhances Plasticity of Cortical-Amygdala Circuits. Neuron 90:1057-70
Zhong, Chongbo; Talmage, David A; Role, Lorna W (2015) Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons. J Vis Exp :e52730
Zhong, Chongbo; Talmage, David A; Role, Lorna W (2013) Nicotine elicits prolonged calcium signaling along ventral hippocampal axons. PLoS One 8:e82719
Jiang, Li; Emmetsberger, Jaime; Talmage, David A et al. (2013) Type III neuregulin 1 is required for multiple forms of excitatory synaptic plasticity of mouse cortico-amygdala circuits. J Neurosci 33:9655-66
Groessl, Florian; Jeong, Jae Hoon; Talmage, David A et al. (2013) Overnight fasting regulates inhibitory tone to cholinergic neurons of the dorsomedial nucleus of the hypothalamus. PLoS One 8:e60828
Mansvelder, Huibert D; Mertz, Marjolijn; Role, Lorna W (2009) Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol 20:432-40

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