Fluorescent Arc/Arg3.1 indicator mice: a versatile tool to study brain activity changes in vitro and in vivo.
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.
Grinevich
Valery
V
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.
Kolleker
Alexander
A
Eliava
Marina
M
Takada
Naoki
N
Takuma
Hiroshi
H
Fukazawa
Yugo
Y
Shigemoto
Ryuichi
R
Kuhl
Dietmar
D
Waters
Jack
J
Seeburg
Peter H
PH
Osten
Pavel
P
D000544:Alzheimer Disease / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D005453:Fluorescence; D049452:Green Fluorescent Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics; D011401:Promoter Regions, Genetic; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000235:genetics; D013312:Stress, Physiological / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D016564:Amyloid beta-Protein Precursor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D058255:Protease Nexins; D011956:Receptors, Cell Surface; C092069:activity regulated cytoskeletal-associated protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins