Obligatory Role of NR2A for Metaplasticity in Visual Cortex

• Published in: Neuron (Cambridge, Mass.) Vol. 53; no. 4; pp. 495 - 502
• Main Authors: Philpot, Benjamin D., Cho, Kathleen K.A., Bear, Mark F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.02.2007; Elsevier Limited
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Action Potentials - radiation effects; Analysis of Variance; Animals; Animals, Newborn; Brain; Brain Chemistry - genetics; Dark Adaptation - physiology; Dose-Response Relationship, Radiation; Electric Stimulation - methods; Gene Expression Regulation - genetics; In Vitro Techniques; Kinases; Light; Mice; Mice, Inbred C57BL; Mice, Knockout; MOLNEURO; Neuronal Plasticity - drug effects; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurons - drug effects; Neurons - physiology; Neurons - radiation effects; Patch-Clamp Techniques - methods; Proteins; Receptors, N-Methyl-D-Aspartate - deficiency; Receptors, N-Methyl-D-Aspartate - physiology; Rodents; Software; Synaptosomes - drug effects; Synaptosomes - metabolism; Synaptosomes - radiation effects; SYSNEURO; Visual Cortex - cytology; SYSNEURO; MOLNEURO
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2007.01.027

Light deprivation lowers the threshold for long-term depression (LTD) and long-term potentiation (LTP) in visual cortex by a process termed metaplasticity, but the mechanism is unknown. The decreased LTD/P threshold correlates with a decrease in the ratio of NR2A to NR2B subunits of cortical NMDA receptors (NMDARs) and a slowing of NMDAR-mediated excitatory postsynaptic currents (EPSCs). However, whether and how changes in NR2 subunit expression contribute to LTD and LTP have been controversial. In the present study, we used an NR2A knockout (KO) mouse to examine the role of this subunit in the experience-dependent modulation of NMDAR properties, LTD, and LTP. We found that deletion of NR2A abrogates the effects of visual experience on NMDAR EPSCs and prevents metaplasticity of LTP and LTD. These data support the hypothesis that experience-dependent changes in NR2A/B are functionally significant and yield a mechanism for an adjustable synaptic modification threshold in visual cortex.