Information on the modulation and synaptic regulation of neuronal nicotinic acetylcholine receptors (AChRs) is at a primitive stage. Of particular interest is the modulation of neuronal AChRs by neural peptides, such as substance P. Since peptide co-existence with classical neurotransmitters is common to both central and peripheral neurons, the mechanism of receptor modulation by peptides is of general importance. In addition to the short term modulation of neuronal ACh responses, the properties and distribution of AChRs may be regulated by synaptogenesis. We will also examine the influence of presynaptic input in the regulation of transmitter sensitivity and neuronal AChR channels.
Our first aim i s to characterize the ACh sensitivity as well as the conductance and kinetics of individual AchRs of embryonic lumbar sympathetic neurons removed just prior to synaptogenesis. These studies use macroscopic ACh-evoked current as well as single channel recording and provide a framework for proposed studies of AChR modulation by peptides and their regulation following synapse formation. We will pursue our initial studies of the role of phosphorylation in peptide modulation of neuronal AChRs by combining physiological and biochemical approaches. We will measure ACh-elicited currents in cells and membrane patches following activation or inhibition of specific kinases. These data will be compared with peptide effects on second messenger metabolism. Finally, we will examine the potential physiological role of modulation and the regulation of AChR properties in innervated sympathetic neurons. In sum, the proposed studies should better define the physiology and biochemical mechanism of AChR modulation as well as the synaptic regulation of this receptor critical to signal transduction at central as well as peripheral synapses.
|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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