Long-term depression of synaptic transmission in the adult mouse insular cortex in vitro.
The insular cortex (IC) is known to play important roles in higher brain functions such as memory and pain. Activity-dependent long-term depression (LTD) is a major form of synaptic plasticity related to memory and chronic pain. Previous studies of LTD have mainly focused on the hippocampus, and no study in the IC has been reported. In this study, using a 64-channel recording system, we show for the first time that repetitive low-frequency stimulation (LFS) can elicit frequency-dependent LTD of glutamate receptor-mediated excitatory synaptic transmission in both superficial and deep layers of the IC of adult mice. The induction of LTD in the IC required activation of the N-methyl-d-aspartate (NMDA) receptor, metabotropic glutamate receptor (mGluR)5, and L-type voltage-gated calcium channel. Protein phosphatase 1/2A and endocannabinoid signaling are also critical for the induction of LTD. In contrast, inhibiting protein kinase C, protein kinase A, protein kinase Mζ or calcium/calmodulin-dependent protein kinase II did not affect LFS-evoked LTD in the IC. Bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine produced another form of LTD in the IC, which was NMDA receptor-independent and could not be occluded by LFS-induced LTD. Our studies have characterised the basic mechanisms of LTD in the IC at the network level, and suggest that two different forms of LTD may co-exist in the same population of IC synapses.
Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea; Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
Ming-Gang
MG
Liu
Kohei
K
Koga
Yan-Yan
YY
Guo
Sukjae Joshua
SJ
Kang
Graham L
GL
Collingridge
Bong-Kiun
BK
Kaang
Ming-Gao
MG
Zhao
Min
M
Zhuo
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression; D051379:Mice; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D063387:Cannabinoid Receptor Antagonists; C578936:Grm5 protein, mouse; D047428:Protein Kinase Inhibitors; D064529:Receptor, Metabotropic Glutamate 5; D016194:Receptors, N-Methyl-D-Aspartate; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2
glutamate receptor; insular cortex; long-term depression; multi-electrode array; protein phosphatase