Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo.
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.
Watson School of Biological Sciences and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Shu-Ling
SL
Chiu
Chih-Ming
CM
Chen
Hollis T
HT
Cline
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000502:physiology* / Q000648:ultrastructure; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013477:Superior Colliculi / Q000166:cytology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014162:Transfection; D014982:Xenopus laevis; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D049452:Green Fluorescent Proteins; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011972:Receptor, Insulin