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Memory and the NMDA Receptors
Tsien, Joe Z.
Article from Journal - ilmiah internasional
The New England Journal of Medicine (keterangan: ada di Proquest) vol. 361 no. 03 (Jul. 2009)
page 302-303 .
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The N-methyl-D-aspartate (NMDA) receptor (NMDAR) is the predominant molecular device for controlling synaptic plasticity and memory function. Thus, an understanding of the control and action of the NMDAR at central synapses may provide clues to therapeutic strategies for treating memory disorders. Episodic and spatial memories, which are often compromised in persons with Alzheimer's disease, critically depend on the hippocampus — in particular, the CA1 area — in both humans and laboratory animals. Blocking the NMDAR in the mouse brain impairs synaptic plasticity and compromises learning and memory. Conversely, genetic enhancement of NMDAR function improves memory in adult mice. Activation of the NMDAR, a major excitatory ligand-gated ion channel in the central nervous system, depends on a couple of coincidental events: the binding of its natural ligand (glutamate) and depolarization — which effects the removal of magnesium ions that otherwise block the ion-channel pore. The NMDAR constitutes the principal cellular machinery responsible for initiating many forms of synaptic plasticity in different areas of the brain. It is a heterotetramer consisting of two obligatory NR1 subunits and two of four possible NR2 subunits: NR2A, NR2B, NR2C, and NR2D. The NR2 subunits in the adult hippocampus and cortex are usually NR2A and NR2B, and the ratio of NR2B to NR2A decreases with age in diverse animal species (including humans), starting from or before the onset of sexual maturity. NR2 composition governs the properties of NMDAR channels and the extent of synaptic plasticity; a relative abundance of NR2B in the juvenile brain confers on it a greater plasticity than the adult brain. The core tetramer associates with a multiprotein complex that includes more than 70 associated proteins, many of which influence the transport, stability, subunit composition, or function of NMDARs.
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