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Free keywords:
Brain ; Gene knockout ; Glutamate receptors ionotropic (AMPA, NMDA) ; Neuron ; Receptor regulation ; NMDA receptor subtype ; kinetics ; postnatal development ; synaptic transmission ; triheteromeric
Abstract:
NMDARs, fundamental to learning
and memory and implicated in certain
neurological disorders, are heterotetrameric
complexes composed of two NR1 and two
NR2 subunits. The function of synaptic
NMDARs in postnatal principal forebrain
neurons is typically attributed to
diheteromeric NR1/NR2A and NR1/NR2B
receptors, despite compelling evidence for
triheteromeric NR1/NR2A/NR2B receptors.
In synapses, the properties of
triheteromeric NMDARs could thus far not
be distinguished from those of mixtures of
diheteromeric NMDARs. To find a
signature of NR1/NR2A/NR2B receptors,
we have employed two gene−targeted mouse
lines, expressing either NR1/NR2A or
NR1/NR2B receptors without
NR1/NR2A/NR2B receptors, and compared
their synaptic properties to those of wild
type. In acute hippocampal slices of
mutants older than four weeks we found a
distinct voltage dependence of NMDA
EPSC decay time for the two diheteromeric
NMDARs. In wild−type mice, NMDA
EPSCs unveiled the NR1/NR2A
characteristic for this voltage−dependent
deactivation exclusively, indicating that the
contribution of NR1/NR2B receptors to
evoked NMDA EPSCs is negligible in adult
CA3−to−CA1 synapses. The presence of
NR1/NR2A/NR2B receptors was obvious
from properties that could not be explained
by a mixture of diheteromeric NR1/NR2A
and NR1/NR2B receptors or by presence of
NR1/NR2A receptors alone. The decay time
for NMDA EPSCs in wild type was slower
than that for NR1/NR2A receptors and the
sensitivity of NMDA EPSCs to NR2Bdirected
NMDAR antagonists was 50%.
Thus, NR2B is prominent in adult
hippocampal synapses as an integral part of
NR1/NR2A/NR2B receptors
