A transgenic mouse model reveals fast nicotinic transmission in hippocampal pyramidal neurons

Eur J Neurosci. 2011 May;33(10):1786-98. doi: 10.1111/j.1460-9568.2011.07671.x. Epub 2011 Apr 19.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcholine / metabolism*
  • Animals
  • Choline O-Acetyltransferase / genetics
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Mice
  • Mice, Transgenic*
  • Nervous System / anatomy & histology
  • Nervous System / metabolism
  • Nicotinic Antagonists / metabolism
  • Patch-Clamp Techniques
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology*
  • Receptors, Nicotinic / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Synaptic Transmission / physiology*
  • Transgenes
  • alpha7 Nicotinic Acetylcholine Receptor


  • Chrna7 protein, mouse
  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Recombinant Fusion Proteins
  • alpha7 Nicotinic Acetylcholine Receptor
  • Choline O-Acetyltransferase
  • Acetylcholine