title: Deprivation-induced synaptic depression by distinct mechanisms in different layers of mouse visual cortex.
abstract: Long-term depression (LTD) induced by low-frequency synaptic stimulation (LFS) was originally introduced as a model to probe potential mechanisms of deprivation-induced synaptic depression in visual cortex. In hippocampus, LTD requires activation of postsynaptic NMDA receptors, PKA, and the clathrin-dependent endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. It has long been assumed that LTD induced in visual cortical layer 2/3 by LFS of layer 4 uses similar mechanisms. Here we show in mouse visual cortex that this conclusion requires revision. We find that LTD induced in layer 2/3 by LFS is unaffected by inhibitors of PKA or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor endocytosis but is reliably blocked by an endocannabinoid CB1 receptor antagonist. Conversely, LFS applied to synapses on layer 4 neurons produces LTD that appears mechanistically identical to that in CA1 and is insensitive to CB1 blockers. Occlusion experiments suggest that both mechanisms contribute to the loss of visual responsiveness after monocular deprivation.
authors.affiliation: Howard Hughes Medical Institute, The Picower Institute for Learning and Memory, Department of Brain and Cognitive Science, Massachusetts Institute of Technology, 177 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Crozier
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Cheng-Hang
authors.initials: CH
authors.lastname: Liu
authors.forename: Mark F
authors.initials: MF
authors.lastname: Bear
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D014793:Visual Cortex / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases