title: Loss of long-term depression in the insular cortex after tail amputation in adult mice.
abstract: The insular cortex (IC) is an important forebrain structure involved in pain perception and taste memory formation. Using a 64-channel multi-electrode array system, we recently identified and characterized two major forms of synaptic plasticity in the adult mouse IC: long-term potentiation (LTP) and long-term depression (LTD). In this study, we investigate injury-related metaplastic changes in insular synaptic plasticity after distal tail amputation. We found that tail amputation in adult mice produced a selective loss of low frequency stimulation-induced LTD in the IC, without affecting (RS)-3,5-dihydroxyphenylglycine (DHPG)-evoked LTD. The impaired insular LTD could be pharmacologically rescued by priming the IC slices with a lower dose of DHPG application, a form of metaplasticity which involves activation of protein kinase C but not protein kinase A or calcium/calmodulin-dependent protein kinase II. These findings provide important insights into the synaptic mechanisms of cortical changes after peripheral amputation and suggest that restoration of insular LTD may represent a novel therapeutic strategy against the synaptic dysfunctions underlying the pathophysiology of phantom pain.
authors.forename: Ming-Gang
authors.initials: MG
authors.lastname: Liu
authors.affiliation: Center for Neuron and Disease, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China. min.zhuo@utoronto.ca.
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D013623:Tail / Q000601:surgery*
chemical_list: D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D005998:Glycine