title: A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons.
abstract: The relative contribution to brain cholinergic signaling by synaptic- and diffusion-based mechanisms remains to be elucidated. In this study, we examined the prevalence of fast nicotinic signaling in the hippocampus. We describe a mouse model where cholinergic axons are labeled with the tauGFP fusion protein driven by the choline acetyltransferase promoter. The model provides for the visualization of individual cholinergic axons at greater resolution than other available models and techniques, even in thick, live, slices. Combining calcium imaging and electrophysiology, we demonstrate that local stimulation of visualized cholinergic fibers results in rapid excitatory postsynaptic currents mediated by the activation of α7-subunit-containing nicotinic acetylcholine receptors (α7-nAChRs) on CA3 pyramidal neurons. These responses were blocked by the α7-nAChR antagonist methyllycaconitine and potentiated by the receptor-specific allosteric modulator 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxanol-3-yl)-urea (PNU-120596). Our results suggest, for the first time, that synaptic nAChRs can modulate pyramidal cell plasticity and development. Fast nicotinic transmission might play a greater role in cholinergic signaling than previously assumed. We provide a model for the examination of synaptic properties of basal forebrain cholinergic innervation in the brain.
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of Colorado, Aurora, CO, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Grybko
authors.forename: Eu-Teum
authors.initials: ET
authors.lastname: Hahm
authors.forename: Wesley
authors.initials: W
authors.lastname: Perrine
authors.forename: Jason A
authors.initials: JA
authors.lastname: Parnes
authors.forename: Wallace S
authors.initials: WS
authors.lastname: Chick
authors.forename: Geeta
authors.initials: G
authors.lastname: Sharma
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Finger
authors.forename: Sukumar
authors.initials: S
authors.lastname: Vijayaraghavan
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009420:Nervous System / Q000033:anatomy & histology / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D019076:Transgenes; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine