Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo

Neuron. 2008 Jun 12;58(5):708-19. doi: 10.1016/j.neuron.2008.04.014.


Insulin receptor signaling has been postulated to play a role in synaptic plasticity; however, the function of the insulin receptor in CNS is not clear. To test whether insulin receptor signaling affects visual system function, we recorded light-evoked responses in optic tectal neurons in living Xenopus tadpoles. Tectal neurons transfected with dominant-negative insulin receptor (dnIR), which reduces insulin receptor phosphorylation, or morpholino against insulin receptor, which reduces total insulin receptor protein level, have significantly smaller light-evoked responses than controls. dnIR-expressing neurons have reduced synapse density as assessed by EM, decreased AMPA mEPSC frequency, and altered experience-dependent dendritic arbor structural plasticity, although synaptic vesicle release probability, assessed by paired-pulse responses, synapse maturation, assessed by AMPA/NMDA ratio and ultrastructural criteria, are unaffected by dnIR expression. These data indicate that insulin receptor signaling regulates circuit function and plasticity by controlling synapse density.

Publication types

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

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Dendrites / physiology*
  • Dendrites / ultrastructure
  • Excitatory Amino Acid Agonists / pharmacology
  • Green Fluorescent Proteins / biosynthesis
  • Microscopy, Electron, Transmission
  • Models, Biological
  • Neuronal Plasticity / physiology*
  • Neurons / cytology*
  • Patch-Clamp Techniques
  • Receptor, Insulin / physiology*
  • Signal Transduction / physiology*
  • Superior Colliculi / cytology
  • Synapses / physiology*
  • Synapses / ultrastructure
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Synaptic Transmission / radiation effects
  • Transfection
  • Xenopus laevis
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Excitatory Amino Acid Agonists
  • Green Fluorescent Proteins
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • Receptor, Insulin