Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) regulates anxiety- and novelty-related behaviors

Genes Brain Behav. 2019 Sep;18(7):e12561. doi: 10.1111/gbb.12561. Epub 2019 Apr 15.

Abstract

The activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1) regulates glutamatergic synapse plasticity and has been linked to neuropsychiatric illness; however, its role in behaviors associated with mood and anxiety disorders remains unclear. We find that stress upregulates Arc expression in the adult mouse nucleus accumbens (NAc)-a brain region implicated in mood and anxiety behaviors. Global Arc knockout mice have altered AMPAR-subunit surface levels in the adult NAc, and the Arc-deficient mice show reductions in anxiety-like behavior, deficits in social novelty preference, and antidepressive-like behavior. Viral-mediated expression of Arc in the adult NAc of male, global Arc KO mice restores normal levels of anxiety-like behavior in the elevated plus maze (EPM). Consistent with this finding, viral-mediated reduction of Arc in the adult NAc reduces anxiety-like behavior in male, but not female, mice in the EPM. NAc-specific reduction of Arc also produced significant deficits in both object and social novelty preference tasks. Together our findings indicate that Arc is essential for regulating normal mood- and anxiety-related behaviors and novelty discrimination, and that Arc's function within the adult NAc contributes to these behavioral effects.

Keywords: AMPAR; Arc/Arg3.1; anxiety; behavior; cellular neuroscience; knockout mouse; novelty; nucleus accumbens; stress; viral-mediated gene transfer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / genetics*
  • Anxiety / physiopathology
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Exploratory Behavior*
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Nucleus Accumbens / metabolism
  • Receptors, AMPA / metabolism
  • Social Behavior

Substances

  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • Receptors, AMPA
  • activity regulated cytoskeletal-associated protein