Visualizing the neuronal activity-regulated gene Arc
Neuronal activity-regulated induction of EGFP-Arc in the hippocampus
Fluorescence images taken from the hippocampus of a transgenic (Tg) mouse kept in a home cage (left panel, naïve) or a Tg mouse that received an electro-convulsive shock 3 hours earlier (right panel, ECS). The framed areas in the upper panels are expanded and shown in the lower panels.
|Activity-dependent gene expression and protein synthesis in mature neurons are required for long-term memory formation. In particular, Arc (also called Arg3.1) has emerged recently as an attractive candidate of cognitive function-related gene products whose induction correlates with physiological neuronal activity. In the postsynaptic density, Arc protein regulates the surface expression of AMPA-type glutamate receptors at excitatory synapses . This function is implicated in several forms of protein translation-dependent synaptic long-term depression and homeostatic plasticity/synaptic scaling. To examine Arc dynamics in living neurons, the expression of a monomeric EGFP-tagged Arc was driven under the control of the 7 kb Arc promoter [2, 3]. Neuronal activity-triggered Arc protein was found to rather accumulate in synapses with low activity, and thus may play a role in an ‘‘inverse” tagging process, to prevent the undesired enhancement of weak synapses in potentiated neurons . Genomic mutations in the Arc gene were recently proposed to be associated with several neurological and psychiatric disorders, including schizophrenia .|
|Depositor||:||Haruhiko Bito, M.D., Ph.D.
Department of Neurochemistry
The University of Tokyo Graduate School of Medicine
|References||:||||Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF. Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron; 52:445-459, 2006.|
|||Kawashima T, Okuno H, Nonaka M, Adachi-Morishima A, Kyo N, Okamura M, Takemoto-Kimura S, Worley PF, Bito H. Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons. Proc Natl Acad Sci U S A.; 106(1):316-321, 2009.|
|||Okuno H, Akashi K, Ishii Y, Yagishita-Kyo N, Suzuki K, Nonaka M, Kawashima T, Fujii H, Takemoto-Kimura S, Abe M, Natsume R, Chowdhury S, Sakimura K, Worley PF, Bito H. Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell; 149(4):886-898, 2012.|
|||Fromer M, Pocklington AJ, Kavanagh DH, et al., De novo mutations in schizophrenia implicate synaptic networks. Nature; 506(7487):179-184, 2014.|
Contact: Shinya Ayabe, Ph.D.
Experimental Animal Division, RIKEN BioResource Center
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