Altered Synaptic and Extrasynaptic NMDA Receptor Properties in Substantia Nigra Dopaminergic Neurons From Mice Lacking the GluN2D Subunit.
Frontiers in cellular neuroscience
MetadataShow full item record
Morris, P. G., Mishina, M., & Jones, S. (2018). Altered Synaptic and Extrasynaptic NMDA Receptor Properties in Substantia Nigra Dopaminergic Neurons From Mice Lacking the GluN2D Subunit.. Frontiers in cellular neuroscience, 12 354. https://doi.org/10.3389/fncel.2018.00354
Abstract N-methyl-D-aspartate receptors (NMDARs) are ubiquitously expressed in the mammalian brain and are essential for neuronal development, survival and plasticity. GluN2 subunit composition has a profound effect on the properties of NMDARs. In substantia nigra dopaminergic (SNc-DA) neurons, pharmacological experiments suggest that the relatively rare GluN2D subunits form functional synaptic and extrasynaptic NMDARs. Given the importance of establishing this point, mice lacking the GluN2D subunit (Grin2D-null) were used in this study to further explore the contribution of the GluN2D subunit to NMDAR responses. Significantly less DQP-1105-sensitive NMDAR-EPSC and significantly more ifenprodil-sensitive NMDAR-EPSC was observed in SNc-DA neurons from Grin2D-null mice, indicating that in these animals a small population of synaptic GluN2D subunits is replaced with GluN2B. Significantly larger currents were seen in response to higher concentrations (1-10 mM) of NMDA in SNc-DA neurons from Grin2D-null mice, as well as significantly more desensitization: these data are consistent with the presence of GluN2D-containing whole-cell NMDARs in SNc-DA neurons, with low conductance and little desensitization. Brief applications of NMDA evoked responses that were significantly less sensitive to DQP-1105 in slices from Grin2D-null mice. Tonic NMDAR activity in response to ambient extracellular glutamate, determined by the sensitivity of tonic current to D-AP5 (50 μM), was significantly less in SNc-DA neurons from Grin2D-null mice. In the presence of the glutamate transporter blocker TBOA (30 μM), the D-AP5-sensitive current was also significantly less in Grin2D-null mice. Taken together, these data support the evidence for GluN2D subunit expression in functional NMDARs at both synaptic and extrasynaptic locations in SNc-DA neurons.
The Wellcome Trust (092611/B/10/Z) BBSRC DTP Studentship to PGM
Wellcome Trust (092611/B/10/Z)
External DOI: https://doi.org/10.3389/fncel.2018.00354
This record's URL: https://www.repository.cam.ac.uk/handle/1810/286247
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/