Evidence for ectopic neurotransmission at a neuronal synapse

Science. 2005 Jul 15;309(5733):446-51. doi: 10.1126/science.1108239.


Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic alpha7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholinesterase / metabolism
  • Algorithms
  • Animals
  • Chick Embryo
  • Computer Simulation*
  • Diffusion
  • Excitatory Postsynaptic Potentials
  • Ganglia, Parasympathetic / physiology*
  • Ganglia, Parasympathetic / ultrastructure
  • Image Processing, Computer-Assisted
  • Mathematics
  • Microscopy, Electron
  • Models, Neurological*
  • Monte Carlo Method*
  • Patch-Clamp Techniques
  • Probability
  • Receptors, Nicotinic / metabolism
  • Sensitivity and Specificity
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Membranes / metabolism
  • Synaptic Transmission*
  • Synaptic Vesicles / metabolism


  • Receptors, Nicotinic
  • nicotinic receptor subunit alpha3
  • Acetylcholinesterase
  • Acetylcholine