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The Journal of Neuroscience, August 15, 2000, 20(16):5899-5905
Developmental Profile of the Changing Properties of NMDA
Receptors at Cerebellar Mossy Fiber-Granule Cell Synapses
Laurence
Cathala,
Charu
Misra, and
Stuart
Cull-Candy
Department of Pharmacology, University College London, London WC1E
6BT, United Kingdom
During cerebellar development, granule cells display well
characterized changes in the expression of NMDA receptor (NMDAR) NR2
subunits, switching from NR2B to NR2A and NR2C in mature cells. Although various studies, including experiments on mutant mice with one
or more NR2 subunit types deleted, suggest that NR2A, NR2B, and NR2C
subunits contribute to synaptic NMDARs, changes in the properties of
the mossy fiber EPSC during development have not been fully evaluated.
In particular, information on NMDAR EPSCs in mature animals is lacking.
We have examined pharmacological and kinetic properties of NMDARs at
mossy fiber-granule cell synapses from their formation to
maturity [postnatal day 7 (P7)-P40 rats]. Significant changes were
seen in the relative amplitudes of the non-NMDAR- and NMDAR-mediated
components of the evoked EPSC and in the decay kinetics of the latter.
The NMDA/non-NMDA ratio was similar at P7, P21, and P40, but showed a
clear peak at P12. This change coincided with a speeding of the NMDAR
EPSC decay, accompanied by a decrease in sensitivity to ifenprodil
(selective NR2B-antagonist). By P21, sensitivity of the NMDAR EPSC to
Mg2+ was approximately threefold less than that at
P12 (IC50, 76 vs 28 µM), suggesting
incorporation of the NR2C subunit. However, the predicted slowing of
decay kinetics to a value more characteristic of NR2C deactivation, was
not seen until P40. Our data are consistent with the known switch from
NR2B to NR2A subunits during the first two postnatal weeks, but suggest
a gradual incorporation of the NR2C subunit that modifies
Mg2+ sensitivity and only later influences EPSC kinetics.
Key words:
cerebellum; granule cells; NMDA receptors; synaptic
transmission; patch-clamp; NMDA subunit expression; NR2C subunit
Copyright © 2000 Society for Neuroscience 0270-6474/00/20165899-07$05.00/0
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