Effects of prefrontal cortex and hippocampal NMDA NR1-subunit deletion on complex cognitive and social behaviors

Janet M. Finlay, Ginger A. Dunham, Analiesse M. Isherwood, Chelsea J. Newton, Thuyanh V. Nguyen, Patricia C. Reppar, Ilana Snitkovski, Sarah A. Paschall, Robert W. Greene

Research output: Contribution to journalArticle

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Abstract

Glutamate N-methyl-d-aspartate receptors (NMDARs) in the medial prefrontal cortex (mPFC) and hippocampus may play an integral role in complex cognitive and social deficits associated with a number of psychiatric illnesses including autism, mood disorders, and schizophrenia. We used localized infusions of adeno-associated virus Cre-recombinase in adult, targeted knock-in mice with loxP sites flanking exons 11-22 of the NR1 gene to investigate the effects of chronic NMDAR dysfunction in the mPFC and CA3 hippocampus on cognitive and social behavior. A 5-choice serial reaction time task (5-CSRTT) was used to monitor aspects of cognitive function that included attention and response inhibition. Social behavior was assessed using Crowley's sociability and preference for social novelty protocol. Chronic NMDAR dysfunction localized to the anterior cingulate/prelimbic mPFC or dorsal CA3 hippocampus differentially affected the response inhibition and social interaction. mPFC NR1-deletion increased perseverative responding in the 5-CSRTT and enhanced preference for social novelty, whereas CA3 NR1-deletion increased premature responding in the 5-CSRTT and decreased social approach behavior. These findings suggest that mPFC and CA3 NMDARs play selective roles in regulating compulsive and impulsive behavior, respectively. Furthermore, these findings are consistent with emerging evidence that these behaviors are mediated by distinct, albeit overlapping, neural circuits. Our data also suggest that NMDARs in these regions uniquely contribute to the expression of normal social behavior. In this case, mPFC and CA3 NMDARs appear to inhibit and facilitate aspects of social interaction, respectively. The latter dissociation raises the possibility that distinct circuits contribute to the expression of social intrusiveness and impoverished social interaction.

Original languageEnglish (US)
Pages (from-to)70-83
Number of pages14
JournalBrain Research
Volume1600
DOIs
StatePublished - Mar 10 2015

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Social Behavior
N-Methylaspartate
Prefrontal Cortex
Interpersonal Relations
Reaction Time
Hippocampus
Dissociative Disorders
Compulsive Behavior
Choice Behavior
Dependovirus
Impulsive Behavior
Gyrus Cinguli
Autistic Disorder
Mood Disorders
Cognition
Psychiatry
aspartic acid receptor
Glutamic Acid
Exons
Schizophrenia

Keywords

  • Attention
  • Hippocampus
  • NMDA receptor
  • Prefrontal cortex
  • Response inhibition
  • Social interaction

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Effects of prefrontal cortex and hippocampal NMDA NR1-subunit deletion on complex cognitive and social behaviors. / Finlay, Janet M.; Dunham, Ginger A.; Isherwood, Analiesse M.; Newton, Chelsea J.; Nguyen, Thuyanh V.; Reppar, Patricia C.; Snitkovski, Ilana; Paschall, Sarah A.; Greene, Robert W.

In: Brain Research, Vol. 1600, 10.03.2015, p. 70-83.

Research output: Contribution to journalArticle

Finlay, JM, Dunham, GA, Isherwood, AM, Newton, CJ, Nguyen, TV, Reppar, PC, Snitkovski, I, Paschall, SA & Greene, RW 2015, 'Effects of prefrontal cortex and hippocampal NMDA NR1-subunit deletion on complex cognitive and social behaviors', Brain Research, vol. 1600, pp. 70-83. https://doi.org/10.1016/j.brainres.2014.10.037
Finlay, Janet M. ; Dunham, Ginger A. ; Isherwood, Analiesse M. ; Newton, Chelsea J. ; Nguyen, Thuyanh V. ; Reppar, Patricia C. ; Snitkovski, Ilana ; Paschall, Sarah A. ; Greene, Robert W. / Effects of prefrontal cortex and hippocampal NMDA NR1-subunit deletion on complex cognitive and social behaviors. In: Brain Research. 2015 ; Vol. 1600. pp. 70-83.
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AU - Nguyen, Thuyanh V.

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