Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors. (15th April 2019)

• Record Type: Journal Article
• Authors: Penrod, Rachel D.; Kumar, Jaswinder; Smith, Laura N.; McCalley, Daniel; Nentwig, Todd B.; Hughes, Brandon W.; Barry, Gabriella M.; Glover, Kelsey; Taniguchi, Makoto; Cowan, Christopher W.
• Is Part Of: Genes, brain, and behavior. Volume 18:Number 7(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2019-04-15
• Subjects: AMPAR -- anxiety -- Arc/Arg3.1 -- behavior -- cellular neuroscience -- knockout mouse -- novelty -- nucleus accumbens -- stress -- viral‐mediated gene transfer; Behavior genetics -- Periodicals; Neurogenetics -- Periodicals; 616.8
• DOI: 10.1111/gbb.12561
• Languages: English
• ISSNs: 1601-1848

Abstract

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. Abstract : Activity‐regulated cytoskeleton‐associated protein acts in the nucleus accumbens to regulate anxiety behavior in a sex‐specific manner.