Molecular and Genetic Determinants of the NMDA Receptor for Superior Learning and Memory FunctionsReport as inadecuate




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The opening-duration of the NMDA receptors implements Hebb-s synaptic coincidence-detection and is long thought to be the rate-limiting factor underlying superior memory. Here, we investigate the molecular and genetic determinants of the NMDA receptors by testing the -synaptic coincidence-detection time-duration- hypothesis vs. -GluN2B intracellular signaling domain- hypothesis. Accordingly, we generated a series of GluN2A, GluN2B, and GluN2D chimeric subunit transgenic mice in which C-terminal intracellular domains were systematically swapped and overexpressed in the forebrain excitatory neurons. The data presented in the present study supports the second hypothesis, the -GluN2B intracellular signaling domain- hypothesis. Surprisingly, we found that the voltage-gated channel opening-durations through either GluN2A or GluN2B are sufficient and their temporal differences are marginal. In contrast, the C-terminal intracellular domain of the GluN2B subunit is necessary and sufficient for superior performances in long-term novel object recognition and cued fear memories and superior flexibility in fear extinction. Intriguingly, memory enhancement correlates with enhanced long-term potentiation in the 10–100 Hz range while requiring intact long-term depression capacity at the 1–5 Hz range.



Author: Stephanie Jacobs , Zhenzhong Cui , Ruiben Feng, Huimin Wang, Deheng Wang, Joe Z. Tsien

Source: http://plos.srce.hr/



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