Insulin induces a novel form of postsynaptic mossy fiber long-term depression in the hippocampus.
The mechanisms of induction and the site of expression of long-term depression (LTD) at the hippocampal mossy fiber-CA3 synapses are not clear. Here, we show that a brief bath application of insulin induces a novel form of mossy fiber LTD. This insulin-LTD is (1) induced and expressed postsynaptically, (2) entirely independent of synaptic stimulation during insulin application, (3) involving a rise in postsynaptic [Ca(2+)](i) and L-type voltage-activated Ca(2+) channel activation, (4) mechanistically distinct from low-frequency stimulation-induced LTD, (5) dependent on phosphatidylinositol 3-kinase signaling, and (6) associated with a clathrin-mediated endocytotic removal of surface 3-hydroxy-5-methylisoxazole-4-propionic acid receptors from the postsynaptic neurons. Moreover, insulin-LTD is specific to mossy fibers to CA3 pyramidal cell synapses, and is not present at associational commissural synapses. These findings not only support a postsynaptic locus of mossy fiber LTD, but also provide a further link between the AMPA receptor trafficking and the bidirectional expression of long-term synaptic plasticity.
Huang
Chiung-Chun
CC
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City 701, Taiwan.
You
Jia-Lin
JL
Lee
Cheng-Che
CC
Hsu
Kuei-Sen
KS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D022163:Clathrin-Coated Vesicles / Q000187:drug effects / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D020746:Calcium Channels, L-Type; D007328:Insulin; D018091:Receptors, AMPA; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin; D005947:Glucose; D002118:Calcium