Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in cortical neurons

Rashna D. Balsara, Ashley N. Ferreira, Deborah L. Donahue, Francis J. Castellino, Patrick L. Sheets

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The spatial distribution of N-methyl-d-aspartate receptor (NMDAR) subunits in layer 5 (L5) neurons of the medial prefrontal cortex (mPFC) is important for integrating input-output signals involved in cognitive functions and motor behavior. In this study, focal laser scanning photostimulation of caged glutamate, slice electrophysiology, and small peptide pharmacology, were used to map the distribution of functional GluN2A and GluN2B subunits of the NMDAR from L5 neurons of wild-type (WT) and GluN2A-/- mice. Focal uncaging of glutamate evoked spatially-restricted glutamatergic responses on various dendritic locations of pyramidal neurons in the mPFC. Analyses of the spatial arrangements of the GluN2A and GluN2B subunits were performed by comparing inhibition of glutamatergic responses in the presence of the GluN2A-selective pharmacological antagonist, NVP-AAM077 (NVP), and the GluN2B-selective peptidic antagonist, conantokin-G (con-G). We found that apical and basal expression and distribution of GluN2A and GluN2B were similar in L5 mPFC neurons of WT mice. However, the inhibition of glutamatergic responses by NVP in brain slices of GluN2A-/- mice were dramatically decreased, while con-G inhibition remained similar to that observed in WT brain slices. The data obtained show that expression and spatial arrangement of GluN2B subunits is independent of GluN2A in L5 neurons of the mPFC. These findings have important ramifications for NMDAR organization and function in L5 pyramidal neurons of the mPFC, and show that specific populations of NMDARs can be antagonized, while sparing other subgroups of NMDARs, thus preserving selective NMDAR functions, an important therapeutic advantage.

Original languageEnglish (US)
Pages (from-to)542-549
Number of pages8
JournalNeuropharmacology
Volume79
DOIs
StatePublished - Apr 1 2014

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Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Neurons
Pyramidal Cells
Glutamic Acid
Pharmacology
Spatial Analysis
Electrophysiology
Brain
Cognition
Lasers
Peptides
aspartic acid receptor
Population
Inhibition (Psychology)
conotoxin GV
Therapeutics

Keywords

  • Conantokins
  • Laser-scanning photostimulation
  • Medial prefrontal cortex
  • NMDARs
  • Pyramidal L5 neurons
  • Slice electrophysiology

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology
  • Medicine(all)

Cite this

Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in cortical neurons. / Balsara, Rashna D.; Ferreira, Ashley N.; Donahue, Deborah L.; Castellino, Francis J.; Sheets, Patrick L.

In: Neuropharmacology, Vol. 79, 01.04.2014, p. 542-549.

Research output: Contribution to journalArticle

Balsara, Rashna D. ; Ferreira, Ashley N. ; Donahue, Deborah L. ; Castellino, Francis J. ; Sheets, Patrick L. / Probing NMDA receptor GluN2A and GluN2B subunit expression and distribution in cortical neurons. In: Neuropharmacology. 2014 ; Vol. 79. pp. 542-549.
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AB - The spatial distribution of N-methyl-d-aspartate receptor (NMDAR) subunits in layer 5 (L5) neurons of the medial prefrontal cortex (mPFC) is important for integrating input-output signals involved in cognitive functions and motor behavior. In this study, focal laser scanning photostimulation of caged glutamate, slice electrophysiology, and small peptide pharmacology, were used to map the distribution of functional GluN2A and GluN2B subunits of the NMDAR from L5 neurons of wild-type (WT) and GluN2A-/- mice. Focal uncaging of glutamate evoked spatially-restricted glutamatergic responses on various dendritic locations of pyramidal neurons in the mPFC. Analyses of the spatial arrangements of the GluN2A and GluN2B subunits were performed by comparing inhibition of glutamatergic responses in the presence of the GluN2A-selective pharmacological antagonist, NVP-AAM077 (NVP), and the GluN2B-selective peptidic antagonist, conantokin-G (con-G). We found that apical and basal expression and distribution of GluN2A and GluN2B were similar in L5 mPFC neurons of WT mice. However, the inhibition of glutamatergic responses by NVP in brain slices of GluN2A-/- mice were dramatically decreased, while con-G inhibition remained similar to that observed in WT brain slices. The data obtained show that expression and spatial arrangement of GluN2B subunits is independent of GluN2A in L5 neurons of the mPFC. These findings have important ramifications for NMDAR organization and function in L5 pyramidal neurons of the mPFC, and show that specific populations of NMDARs can be antagonized, while sparing other subgroups of NMDARs, thus preserving selective NMDAR functions, an important therapeutic advantage.

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