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.
Chiu
Shu-Ling
SL
Watson School of Biological Sciences and Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Chen
Chih-Ming
CM
Cline
Hollis T
HT
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