Fluorescent Arc/Arg3.1 indicator mice: a versatile tool to study brain activity changes in vitro and in vivo

J Neurosci Methods. 2009 Oct 30;184(1):25-36. doi: 10.1016/j.jneumeth.2009.07.015. Epub 2009 Jul 21.


The brain-specific immediate early gene Arc/Arg3.1 is induced in response to a variety of stimuli, including sensory and behavior-linked neural activity. Here we report the generation of transgenic mice, termed TgArc/Arg3.1-d4EGFP, expressing a 4-h half-life form of enhanced green fluorescent protein (d4EGFP) under the control of the Arc/Arg3.1 promoter. We show that d4EGFP-mediated fluorescence faithfully reports Arc/Arg3.1 induction in response to physiological, pathological and pharmacological stimuli, and that this fluorescence permits electrical recording from activated neurons in the live mouse. Moreover, the fluorescent Arc/Arg3.1 indicator revealed activity changes in circumscribed brain areas in distinct modes of stress and in a mouse model of Alzheimer's disease. These findings identify the TgArc/Arg3.1-d4EGFP mouse as a versatile tool to monitor Arc/Arg3.1 induction in neural circuits, both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / physiopathology
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Brain / drug effects
  • Brain / physiology*
  • Brain / physiopathology
  • Cytoskeletal Proteins / genetics*
  • Disease Models, Animal
  • Fluorescence
  • Green Fluorescent Proteins / genetics*
  • Green Fluorescent Proteins / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / genetics*
  • Neurons / drug effects
  • Neurons / physiology*
  • Presenilin-1 / genetics
  • Presenilin-2 / genetics
  • Promoter Regions, Genetic
  • Protease Nexins
  • Receptors, Cell Surface / genetics
  • Stress, Physiological / drug effects
  • Stress, Physiological / physiology
  • Time Factors


  • Amyloid beta-Protein Precursor
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2
  • Protease Nexins
  • Receptors, Cell Surface
  • activity regulated cytoskeletal-associated protein
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins