NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus

• Type of Material: Article
• Authors: Sharon A. Swanger, Emory University; Katie M. Vance, Emory University; Jean-François Pare, Emory University; Florence Sotty, Division of Neurodegeneration and Biologics, Denmark; Karina Fog, Division of Neurodegeneration and Biologics, Denmark; Yoland Smith, Emory University; Stephen Traynelis, Emory University
• Language: English
• Date: 2015-12-02
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Final Published Version
• Copyright Statement: ©2015 the authors.
• Final Published Version (URL): http://dx.doi.org/10.1523/JNEUROSCI.1702-15.2015
• Title of Journal or Parent Work: Journal of Neuroscience Nursing
• ISSN: 0888-0395
• Volume: 35
• Issue: 48
• Start Page: 15971
• End Page: 15983
• Keywords: subthalamic nucleus; Science & Technology; GluN2B; Life Sciences & Biomedicine; COMPACTA DOPAMINERGIC-NEURONS; POSTNATAL-DEVELOPMENT; GluN2D; METABOTROPIC GLUTAMATE RECEPTORS; glutamate receptor; RAT-BRAIN; NMDA; Neurosciences & Neurology; PARKINSONS-DISEASE; Neurosciences; excitatory synapse; METHYL-D-ASPARTATE; GLOBUS-PALLIDUS; DIFFERENTIAL EXPRESSION; HUMAN BASAL GANGLIA; EXCITATORY POSTSYNAPTIC CURRENTS
• Research Categories: Health Sciences, Pharmacology; Health Sciences, General

Abstract

The GluN2D subunit of the NMDA receptor is prominently expressed in the basal ganglia and associated brainstem nuclei, including the subthalamic nucleus (STN), globus pallidus, striatum, and substantia nigra. However, little is known about how GluN2D-containing NMDA receptors contribute to synaptic activity in these regions. Using Western blotting of STN tissue punches, we demonstrated that GluN2D is expressed in the rat STN throughout development [age postnatal day 7 (P7)-P60] and in the adult (age P120). Immunoelectron microscopy of the adult rat brain showed that GluN2D is predominantly expressed in dendrites, unmyelinated axons, and axon terminals within the STN. Using subunit-selective allosteric modulators of NMDA receptors (TCN-201, ifenprodil, CIQ, and DQP-1105), we provide evidence that receptors containing the GluN2B and GluN2D subunits mediate responses to exogenously applied NMDA and glycine, as well as synaptic NMDA receptor activation in the STN of rat brain slices. EPSCs in the STN were mediated primarily by AMPA and NMDA receptors and GluN2D-containing NMDA receptors controlled the slow deactivation time course of EPSCs in the STN. In vivo recordings from the STN of anesthetized adult rats demonstrated that the spike firing rate was increased by the GluN2C/D potentiator CIQ and decreased by the GluN2C/D antagonist DQP-1105, suggesting that NMDA receptor activity can influence STN output. These data indicate that the GluN2B and GluN2D NMDA receptor subunits contribute to synaptic activity in the STN and may represent potential therapeutic targets for modulating subthalamic neuron activity in neurological disorders such as Parkinson’s disease.