Adult forebrain NMDA receptors gate social motivation and social memory

Stephanie Jacobs, Joe Z. Tsien

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Motivation to engage in social interaction is critical to ensure normal social behaviors, whereas dysregulation in social motivation can contribute to psychiatric diseases such as schizophrenia, autism, social anxiety disorders and post-traumatic stress disorder (PTSD). While dopamine is well known to regulate motivation, its downstream targets are poorly understood. Given the fact that the dopamine 1 (D1) receptors are often physically coupled with the NMDA receptors, we hypothesize that the NMDA receptor activity in the adult forebrain principal neurons are crucial not only for learning and memory, but also for the proper gating of social motivation. Here, we tested this hypothesis by examining sociability and social memory in inducible forebrain-specific NR1 knockout mice. These mice are ideal for exploring the role of the NR1 subunit in social behavior because the NR1 subunit can be selectively knocked out after the critical developmental period, in which NR1 is required for normal development. We found that the inducible deletion of the NMDA receptors prior to behavioral assays impaired, not only object and social recognition memory tests, but also resulted in profound deficits in social motivation. Mice with ablated NR1 subunits in the forebrain demonstrated significant decreases in sociability compared to their wild type counterparts. These results suggest that in addition to its crucial role in learning and memory, the NMDA receptors in the adult forebrain principal neurons gate social motivation, independent of neuronal development.

Original languageEnglish (US)
Pages (from-to)164-172
Number of pages9
JournalNeurobiology of Learning and Memory
Volume138
DOIs
StatePublished - Feb 1 2017

Keywords

  • NMDA receptor
  • NR1 knockout
  • Sociability
  • Social memory
  • Social motivation

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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