TY - JOUR
T1 - Distinct Modes of AMPA Receptor Suppression at Developing Synapses by GluN2A and GluN2B
T2 - Single-Cell NMDA Receptor Subunit Deletion In Vivo
AU - Gray, John
AU - Shi, Yun
AU - Usui, Hiroshi
AU - During, Matthew J.
AU - Sakimura, Kenji
AU - Nicoll, Roger A.
PY - 2011/9/22
Y1 - 2011/9/22
N2 - During development there is an activity-dependent switch in synaptic N-Methyl-D-aspartate (NMDA) receptor subunit composition from predominantly GluN2B to GluN2A, though the precise role of this switch remains unknown. By deleting GluN2 subunits in single neurons during synaptogenesis, we find that both GluN2B and GluN2A suppress AMPA receptor expression, albeit by distinct means. Similar to GluN1, GluN2B deletion increases the number of functional synapses, while GluN2A deletion increases the strength of unitary connections without affecting the number of functional synapses. We propose a model of excitatory synapse maturation in which baseline activation of GluN2B-containing receptors prevents premature synapse maturation until correlated activity allows induction of functional synapses. This activity also triggers the switch to GluN2A, which dampens further potentiation. Furthermore, we analyze the subunit composition of synaptic NMDA receptors in CA1 pyramidal cells, provide electrophysiological evidence for a large population of synaptic triheteromeric receptors, and estimate the subunit-dependent open probability.
AB - During development there is an activity-dependent switch in synaptic N-Methyl-D-aspartate (NMDA) receptor subunit composition from predominantly GluN2B to GluN2A, though the precise role of this switch remains unknown. By deleting GluN2 subunits in single neurons during synaptogenesis, we find that both GluN2B and GluN2A suppress AMPA receptor expression, albeit by distinct means. Similar to GluN1, GluN2B deletion increases the number of functional synapses, while GluN2A deletion increases the strength of unitary connections without affecting the number of functional synapses. We propose a model of excitatory synapse maturation in which baseline activation of GluN2B-containing receptors prevents premature synapse maturation until correlated activity allows induction of functional synapses. This activity also triggers the switch to GluN2A, which dampens further potentiation. Furthermore, we analyze the subunit composition of synaptic NMDA receptors in CA1 pyramidal cells, provide electrophysiological evidence for a large population of synaptic triheteromeric receptors, and estimate the subunit-dependent open probability.
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U2 - 10.1016/j.neuron.2011.08.007
DO - 10.1016/j.neuron.2011.08.007
M3 - Article
C2 - 21943605
AN - SCOPUS:80052188595
VL - 71
SP - 1085
EP - 1101
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -