Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats

Brionna D. Davis-Reyes, Veronica M. Campbell, Michelle A. Land, Holly L. Chapman, Susan J. Stafford, Noelle Anastasio

Research output: Contribution to journalArticle

Abstract

Impulsivity is a multifaceted behavioral manifestation with implications in several neuropsychiatric disorders. Glutamate neurotransmission through the N-methyl-D-aspartate receptors (NMDARs) in the medial prefrontal cortex (mPFC), an important brain region in decision-making and goal-directed behaviors, plays a key role in motor impulsivity. We discovered that inherent motor impulsivity predicted responsiveness to D-cycloserine (DCS), a partial NMDAR agonist, which prompted the hypothesis that inherent motor impulsivity is associated with the pattern of expression of cortical NMDAR subunits (GluN1, GluN2A, GluN2B), specifically the protein levels and synaptosomal trafficking of the NMDAR subunits. Outbred male Sprague-Dawley rats were identified as high (HI) or low (LI) impulsive using the one-choice serial reaction time task. Following phenotypic identification, mPFC synaptosomal protein was extracted from HI and LI rats to assess the expression pattern of the NMDAR subunits. Synaptosomal trafficking and stabilization for the GluN2 subunits were investigated by co-immunoprecipitation for postsynaptic density 95 (PSD95) and synapse associated protein 102 (SAP102). HI rats had lower mPFC GluN1 and GluN2A, but higher GluN2B and pGluN2B synaptosomal protein expression versus LI rats. Further, higher GluN2B:PSD95 and GluN2B:SAP102 protein:protein interactions were detected in HI versus LI rats. Thus, the mPFC NMDAR subunit expression pattern and/or synaptosomal trafficking associates with high inherent motor impulsivity. Increased understanding of the complex regulation of NMDAR balance within the mPFC as it relates to inherent motor impulsivity may lead to a better understanding of risk factors for impulse-control disorders.

Original languageEnglish (US)
Pages (from-to)204-213
Number of pages10
JournalBiochemical Pharmacology
Volume168
DOIs
StatePublished - Oct 1 2019

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Impulsive Behavior
N-Methyl-D-Aspartate Receptors
Rats
Prefrontal Cortex
Proteins
Post-Synaptic Density
Synapses
Disruptive, Impulse Control, and Conduct Disorders
Cycloserine
Immunoprecipitation
Synaptic Transmission
Reaction Time
Sprague Dawley Rats
Glutamic Acid
Brain
Decision Making
Stabilization
Decision making

Keywords

  • D-cycloserine
  • MAGUKs
  • Medial prefrontal cortex
  • Motor impulsivity
  • NMDA receptor

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats. / Davis-Reyes, Brionna D.; Campbell, Veronica M.; Land, Michelle A.; Chapman, Holly L.; Stafford, Susan J.; Anastasio, Noelle.

In: Biochemical Pharmacology, Vol. 168, 01.10.2019, p. 204-213.

Research output: Contribution to journalArticle

Davis-Reyes, Brionna D. ; Campbell, Veronica M. ; Land, Michelle A. ; Chapman, Holly L. ; Stafford, Susan J. ; Anastasio, Noelle. / Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats. In: Biochemical Pharmacology. 2019 ; Vol. 168. pp. 204-213.
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AB - Impulsivity is a multifaceted behavioral manifestation with implications in several neuropsychiatric disorders. Glutamate neurotransmission through the N-methyl-D-aspartate receptors (NMDARs) in the medial prefrontal cortex (mPFC), an important brain region in decision-making and goal-directed behaviors, plays a key role in motor impulsivity. We discovered that inherent motor impulsivity predicted responsiveness to D-cycloserine (DCS), a partial NMDAR agonist, which prompted the hypothesis that inherent motor impulsivity is associated with the pattern of expression of cortical NMDAR subunits (GluN1, GluN2A, GluN2B), specifically the protein levels and synaptosomal trafficking of the NMDAR subunits. Outbred male Sprague-Dawley rats were identified as high (HI) or low (LI) impulsive using the one-choice serial reaction time task. Following phenotypic identification, mPFC synaptosomal protein was extracted from HI and LI rats to assess the expression pattern of the NMDAR subunits. Synaptosomal trafficking and stabilization for the GluN2 subunits were investigated by co-immunoprecipitation for postsynaptic density 95 (PSD95) and synapse associated protein 102 (SAP102). HI rats had lower mPFC GluN1 and GluN2A, but higher GluN2B and pGluN2B synaptosomal protein expression versus LI rats. Further, higher GluN2B:PSD95 and GluN2B:SAP102 protein:protein interactions were detected in HI versus LI rats. Thus, the mPFC NMDAR subunit expression pattern and/or synaptosomal trafficking associates with high inherent motor impulsivity. Increased understanding of the complex regulation of NMDAR balance within the mPFC as it relates to inherent motor impulsivity may lead to a better understanding of risk factors for impulse-control disorders.

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