Activity-dependent regulation of NR2B translation contributes to metaplasticity in mouse visual cortex.
Visual experience and deprivation bidirectionally modify the NR2A and NR2B subunit composition of NMDARs, and these changes in turn modify the properties of synaptic plasticity in the visual cortex. Deprivation-induced lowering of the NR2A/2B ratio can occur by altering either NR2A or NR2B protein levels, but how a reduction in synaptic activity regulates these changes in a subunit-specific manner is poorly understood. Here, we find that visual deprivation in juvenile mice by dark-rearing or monocular lid suture reduces the NR2A/2B ratio in the deprived cortex in temporally distinct phases--initially by increasing NR2B protein levels, and later by decreasing NR2A protein levels. Brief dark-exposure of juvenile rats likewise produces an increase in NR2B expression. Furthermore, we are able to model the early increase in NR2B by blocking NMDARs in vitro, and we find that translation of NR2B is likely a major point of regulation. Translation of NR2A is not regulated in this manner. Therefore, the differential translational regulation of NR2A and NR2B may contribute to experience-dependent modification of NMDAR subunit composition.
Chen
Wendy S
WS
Department of Neuroscience, Brown University, Box 1953, Providence, RI 02912, USA.
Bear
Mark F
MF
D020757:Amaurosis Fugax / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D003624:Darkness; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D007839:Functional Laterality / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D011247:Pregnancy; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012683:Sensory Deprivation / Q000502:physiology; D013997:Time Factors; D014793:Visual Cortex / Q000378:metabolism* / Q000648:ultrastructure
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate