抄録
While NMDA-type ionotropic glutamate receptor (NMDAR) is widely accepted as a key regulator for certain forms of memory and learning and LTP induction, not much is known about how NMDAR function is regulated at physiological circumstances. The NR2B subunit of the NMDAR is tyrosine phosphorylated in brain, with Tyr-1472 as a major phosphorylation site. Phosphorylation of neural proteins is one of the main mechanisms underlying dynamic changes in neural functions, so we investigated the physiological significance of NR2B phosphorylation in neuronal plasticity and learning behavior. Mice with a knockin mutation of the Tyr-1472 site to phenylalanine (Y1472F) showed impaired induction of amygdaloid long-term potentiation and fear-related learning. Basic properties of synaptic transmission were normal in YF/YF mice, suggesting that impaired LTP in YF/YF mice is not caused by direct modification of NMDAR current properties but is associated with some intracellular signaling downstream from NMDAR activation. In fact, CaM kinase II, a key regulator for synaptic plasticity was undetectable in NMDAR complex of YF/YF mice. Electron microscopic analyses revealed that NMDAR localization at synapses was impaired in YF/YF mice, presumably resulting in altered NMDAR complex of YF/YF mice. These results strongly argue that phosphorylation of Tyr-1472 regulates NMDAR localization at synapses leading to modulating synaptic plasticity and fear-related learning. [J Physiol Sci. 2006;56 Suppl:S24]
