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Author Notes:

Correspondence should be addressed to Dr. Stephen F. Traynelis, Department of Pharmacology, Rollins Research Center, Emory University School of Medicine, 1510 Clifton Rd., Atlanta, GA 30322., Email: strayne@emory.edu

Author contributions: S.A.S., K.M.V., J.-F.P., F.S., K.F., Y.S., and S.F.T. designed research; S.A.S., K.M.V., J.-F.P., and F.S. performed research; S.A.S., K.M.V., J.-F.P., F.S., K.F., Y.S., and S.F.T. analyzed data; S.A.S., K.M.V., F.S., K.F., Y.S., and S.F.T. wrote the paper.

S.A.S. and K.M.V. contributed equally to this work.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • excitatory synapse
  • GluN2B
  • GluN2D
  • glutamate receptor
  • NMDA
  • subthalamic nucleus
  • METHYL-D-ASPARTATE
  • EXCITATORY POSTSYNAPTIC CURRENTS
  • METABOTROPIC GLUTAMATE RECEPTORS
  • COMPACTA DOPAMINERGIC-NEURONS
  • HUMAN BASAL GANGLIA
  • PARKINSONS-DISEASE
  • RAT-BRAIN
  • DIFFERENTIAL EXPRESSION
  • POSTNATAL-DEVELOPMENT
  • GLOBUS-PALLIDUS

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

Tools:

Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 35, Number 48

Publisher:

, Pages 15971-15983

Type of Work:

Article | Final Publisher PDF

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.

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©2015 the authors.

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