Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity

@article{Liu2004RoleON,
  title={Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity},
  author={Lidong Liu and Tak Pan Wong and Mario F. Pozza and Kurt Lingenhoehl and Yushan Wang and Morgan Sheng and Yves P. Auberson and Yu Tian Wang},
  journal={Science},
  year={2004},
  volume={304},
  pages={1021 - 1024}
}
Activation of N-methyl-d-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit… 
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A model for synaptic development regulated by NMDA receptor subunit expression

It is demonstrated that the NMDAR subunit switch contributes to inducing two consecutive processes—the potentiation of weak synapses and the induction of the competition between them—at an adequately rapid rate.

Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity

The model suggests that Ca2+ influx into the postsynaptic spine via different subtypes of NMDARs makes up a "final common pathway", controlling synaptic plasticity by its magnitude and temporal pattern regardless of the source.

The role of NMDAR subtypes and charge transfer during hippocampal LTP induction

The magnitude of hippocampal long term depression depends on the synaptic location of activated NR2-containing N-methyl-d-aspartate receptors

Activation of extrasynaptic NMDA receptors induces LTD in rat hippocampal CA1 neurons

The Role of NMDA Receptor Subtypes in Short-Term Plasticity in the Rat Entorhinal Cortex

The data suggest that NMDAr involved in presynaptic plasticity in layer V are exclusively NR1/NR2B diheteromers, whilst postsynaptically they are probably a mixture of NR1/.

Rapid Bidirectional Switching of Synaptic NMDA Receptors

Different NMDA receptor subtypes mediate induction of long‐term potentiation and two forms of short‐term potentiation at CA1 synapses in rat hippocampus in vitro

It is suggested that the mechanistic separation of STP and LTP is likely to have important functional implications in that these two forms of synaptic plasticity can subserve unique physiological functions in a behaving animal.

Activation of NR2B-containing NMDA receptors is not required for NMDA receptor-dependent long-term depression

Involvement of synaptic NR2B-containing NMDA receptors in long-term depression induction in the young rat visual cortex in vitro.

It is found that LTD was readily induced in layer II/III pyramidal neurons of the rat visual cortex with 10-min 1-Hz stimulation paired with postsynaptic depolarization, and the results suggest that the induction of LTD is NMDAR-dependent and requires NR2B-containing N MDARs, not NR2A-containingNMDARs.
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References

SHOWING 1-10 OF 35 REFERENCES

Intracellular Domains of NMDA Receptor Subtypes Are Determinants for Long-Term Potentiation Induction

Besides NMDA receptor-mediated Ca2+ influx, subtype-specific signaling is critical for LTP induction, with the intracellular C-terminal domain of the NR2 subunits directing signaling pathways with an age-dependent preference.

Synaptic plasticity: LTP and LTD

Two Forms of Synaptic Plasticity with Distinct Dependence on Age, Experience, and NMDA Receptor Subtype in Rat Visual Cortex

The results implicate NR2 subunit composition in the regulation of neocortical plasticity and demonstrate differential subunit regulation at inhibitory and excitatory connections.

Calcium stores regulate the polarity and input specificity of synaptic modification

Reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-d-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs.

Changing subunit composition of heteromeric NMDA receptors during development of rat cortex

Direct evidence is presented that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits.

Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor ε1 subunit

It is shown that targeted disruption of the mouse εl subunit gene resulted in significant reduction of the NMDA receptor channel current and long-term potentiation at the hippocampal CA1 synapses, which supports the notion that the NMda receptor channel-dependent synaptic plasticity is the cellular basis of certain forms of learning.

Importance of the Intracellular Domain of NR2 Subunits for NMDA Receptor Function In Vivo

A synaptic model of memory: long-term potentiation in the hippocampus

The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.

The Incorporation of NMDA Receptors with a Distinct Subunit Composition at Nascent Hippocampal Synapses In Vitro

The data indicate that the synaptic NMDA receptor complement changes quickly after synapse formation, and suggests that synapses containing predominately NR1/NR2B heteromers represent “immature” sites, whereas mature sites express NMDA receptors with a distinct, presumably triheteromeric, subunit composition.

Ras and Rap Control AMPA Receptor Trafficking during Synaptic Plasticity