NR2A and NR2B subunit containing NMDA receptors differentially regulate striatal output pathways
Open Access
- 15 September 2007
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 103 (6), 2200-2211
- https://doi.org/10.1111/j.1471-4159.2007.04966.x
Abstract
Triple probe microdialysis was employed to investigate whether striatal NR2A and NR2B subunit containing NMDA receptors regulate the activity of striato-pallidal and striato-nigral projection neurons. Probes were implanted in the striatum, ipsilateral globus pallidus and substantia nigra reticulata. Intrastriatal perfusion with the NR2A subunit selective antagonist (R)-[(S)-1-(4-bromo-phenyl)-ethylamino]-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid (NVP-AAM077) reduced pallidal GABA and increased nigral glutamate (GLU) release whereas perfusion with the NR2B subunit selective antagonist (R-(R*,S*)-α-(4-hydroxyphenyl)-β-methyl-4-(phenylmethyl)-1-piperidinepropanol (Ro 25-6981) reduced nigral GABA and elevated striatal and pallidal GLU release. To confirm that changes in GABA levels were because of blockade of (GLUergic-driven) tonic activity of striatofugal neurons, tetrodotoxin was perfused in the striatum. Tetrodotoxin reduced both pallidal and nigral GABA release without changing GLU levels. To investigate whether striatal NR2A and NR2B subunits were also involved in phasic activation of striatofugal neurons, NVP-AAM077 and Ro 25-6981 were challenged against a NMDA concentration able to evoke GABA release in the three areas. Both antagonists prevented the NMDA-induced striatal GABA release. NVP-AAM077 also prevented the NMDA-induced surge in GABA release in the globus pallidus, whereas Ro 25-6981 attenuated it in the substantia nigra. We conclude that striatal NMDA receptors containing NR2A and NR2B subunits preferentially regulate the striato-pallidal and striato-nigral projection neurons, respectively.Keywords
This publication has 53 references indexed in Scilit:
- Contribution of NR2A and NR2B NMDA subunits to bidirectional synaptic plasticity in the hippocampus in vivoHippocampus, 2006
- Lack of NMDA Receptor Subtype Selectivity for Hippocampal Long-Term PotentiationJournal of Neuroscience, 2005
- Structure–activity analysis of a novel NR2C/NR2D‐preferring NMDA receptor antagonist: 1‐(phenanthrene‐2‐carbonyl) piperazine‐2,3‐dicarboxylic acidBritish Journal of Pharmacology, 2004
- Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: Intrastriatal microinjection studies in the 6‐OHDA‐lesioned ratMovement Disorders, 2002
- Evidence for native NMDA receptor subtype pharmacology as revealed by differential effects on the NMDA-evoked release of striatal neuromodulators: Eliprodil, ifenprodil and other native NMDA receptor subtype selective compoundsNeurochemistry International, 1996
- Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit compositionEuropean Journal of Pharmacology: Molecular Pharmacology, 1994
- Heterogeneity of N‐Methyl‐D‐Aspartate Receptors Regulating the Release of Dopamine and Acetylcholine from Striatal SlicesJournal of Neurochemistry, 1991
- Disinhibition as a basic process in the expression of striatal functionsTrends in Neurosciences, 1990
- The functional anatomy of basal ganglia disordersTrends in Neurosciences, 1989
- Behavioural effects of N-methyl-D-aspartate in the anterodorsal striatum of the ratLife Sciences, 1988