Long-term depression requires postsynaptic AMPA GluR2 receptor in adult mouse cingulate cortex.
Synaptic long-term depression (LTD) is thought to be important for various brain functions such as learning, memory, and development. Although anterior cingulated cortex (ACC) has been demonstrated to contribute to learning and memory, no studies has been reported about the synaptic mechanisms for cingulate LTD. Here, we used integrative genetic, pharmacological and electrophysiological approaches to demonstrate that AMPA GluR2, but not GluR3, subunit is critical for cingulate LTD. We found that LTD was absent in adult cingulate slices of GluR2 knockout mice. Furthermore, postsynaptic injections of peptides that inhibit AMPA GluR2-PDZ interactions blocked the induction of LTD. To determine if the requirement for AMPA receptor-PDZ interaction is time-dependent, we injected the same inhibiting peptide into the postsynaptic cells 5 min after the induction of LTD. We found that LTD was not affected by the peptide, providing the first evidence that postsynaptic AMPA GluR2-mediated depression occurs rapidly (within t = 5 min). Genetic deletion of GluR3 did not affect cingulate LTD. Our results provide the first study of cingulate LTD mechanism using whole-cell patch-clamp recording in adult cortical slices and demonstrate that postsynaptic AMPA GluR2 subunit is crucial for synaptic depression in the ACC of adult mice.
Toyoda
Hiroki
H
Department of Physiology, Faculty of Medicine, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, Ontario, Canada.
Wu
Long-Jun
LJ
Zhao
Ming-Gao
MG
Xu
Hui
H
Jia
Zhengping
Z
Zhuo
Min
M
D000779:Anesthetics, Local; D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D006179:Gyrus Cinguli / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D018091:Receptors, AMPA / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D009435:Synaptic Transmission; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D000779:Anesthetics, Local; D008565:Membrane Proteins; D009842:Oligopeptides; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3; C012647:QX-314; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D008012:Lidocaine; C104722:glutamate receptor ionotropic, AMPA 2