[Abstract Title]. - Society for Neuroscience

Disclosures: M.A. de Souza Silva, None; B. Topic, None; C. Mattern , None; J.P. Huston,
None.
Poster
273. Basal Ganglia: Transmitters and Neuromodulation I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 273.5/II20
Topic: D.15.a. Transmitters and neuromodulation
Support: USPHS NS33538
Title: NR2A and NR2B receptor subunits differentially contribute to NMDA currents in D1- and
D2 receptor-expressing medium-sized striatal neurons
Authors: *E. L. JOCOY, V. M. ANDRE, Y. E. FISHER, M. S. LEVINE;
MRRC, UCLA, Los Angeles, CA
Abstract: Subpopulations of medium-sized striatal neurons (MSNs) primarily express either D1
(D1R) or D2 (D2R) dopamine receptors. Both subpopulations express N-methyl-D-aspartate
receptors (NMDARs) with NR1, NR2A and/or NR2B subunits. This study determined if NR2
subunit composition affects NMDAR-mediated currents differentially in D1R- and D2Rexpressing
MSNs. Mice expressing the reporter gene enhanced green fluorescent protein (EGFP)
under the control of promoters for either D1Rs or D2Rs were crossed with mice in which the
NR2A subunit was removed (NR2AKO). MSNs from striatal slices were acutely isolated,
voltage-clamped at -70 mV in 0 Mg 2+ and NMDA was applied to evaluate NMDAR-mediated
currents. NMDA dose-responses (100, 500 and 1000 κM) were compared between MSNs from
wildtype (WT) and NR2AKOs. Deletion of NR2A led to significant reductions in NMDARmediated
currents and current densities in D1R-expressing MSNs compared to those from WT
littermates. In contrast, currents and current densities did not differ between D2R-expressing WT
and D2R-expressing NR2AKOs, suggesting the lack of a significant role for NR2A subunits in
D2R-expressing MSNs. To more specifically examine the role of NR2B subunits, the NR2B
antagonist ifenprodil (.1, 1 and 10 κM) was applied in the presence of NMDA. Peak NMDARmediated
currents from D2R-expressing WTs were attenuated by ifenprodil significantly more
than those from D1R-expressing WTs, suggesting that D2R-expressing MSNs have more
functional NR2B-containing receptors than D1R-expressing MSNs. Although, ifenprodil
sensitivity was higher in NR2AKOs than in WTs for both D1R- and D2R-expressing MSNs, no
differences were observed between D1R-expressing NR2AKOs and D2R-expressing NR2AKOs.
These data suggest that deletion of NR2A results in similar changes to NR2B-containing
receptors in D1R- and D2R-expressing neurons and that the lack of a difference in NMDA dose-