Abstract
The activity-regulated cytoskeletal-associated protein (Arc) is an immediate-early gene (IEG) that is dynamically regulated by neuronal activity. IEGs encode a diverse range of proteins including regulatory transcription factors, structural and signal transduction proteins, growth factors, proteases, and enzymes [reviewed in (Lanahan and Worley, 1998)]. Moreover, several IEGs have been shown to be required for long-lasting synaptic plasticity and memory consolidation processes [reviewed in (authorch19:guzowski2002, yearch19:guzowski2002)]. Of the IEGs investigated in learning and memory, Arc, also referred to as Arg3.1 (activity-regulated gene 3.1), has been of particular interest because of its tight experience-dependent regulation in behaviorally defined neural networks, its mRNA transport to and expression in activated synapses, its capacity for modification of synaptic function, and its critical role in memory consolidation. This chapter provides an overview of the research on Arc’s properties, putative functions, and regulation at cellular and network levels.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adams, J.P. and Dudek, S.M. (2005) Late-phase long-term potentiation: getting to the nucleus. Nat. Rev. Neurosci. 6, 737–743.
Agnihotri, N.T., Hawkins, R.D., Kandel, E.R. and Kentros, C. (2004) The long-term stability of new hippocampal place fields requires new protein synthesis. Proc. Natl. Acad. Sci. USA 101, 3656–3661.
Berridge, M.J. (1998) Neuronal calcium signaling. Neuron 21, 13–26.
Brakeman, P.R., Lanahan, A.A., O’Brien, R., Roche, K., Barnes, C.A., Huganir, R.L. and Worley, P.F. (1997) Homer: A protein that selectively binds metabotropic glutamate receptors. Nature 386, 284–288.
Burke, S.N., Chawla, M.K., Penner, M.R., Crowell, B.E., Worley, P.F., Barnes, C.A. and McNaughton, B.L. (2005) Differential encoding of behavior and spatial context in deep and superficial layers of the neocortex. Neuron 45, 667–674.
Chawla, M.K., Guzowski, J.F., Ramirez-Amaya, V., Lipa, P., Hoffman, K.L., Marriott, L.K., P.F., McNaughton, B.L. and Barnes, C.A. (2005) Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience. Hippocampus 15, 579–586.
Chowdhury, S., Shepherd, J.D., Okuno, H., Lyford, G., Petralia, R.S., Plath, N., Kuhl, D., Huganir, R.L. and Worley, P.F. (2006) Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 52, 445–459.
Chwang, W.B., O’Riordan, K.J., Levenson, J.M. and Sweatt, J.D. (2006) ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning. Learn. Mem. 13, 322–328.
Dickey, C.A., Gordon, M.N., Mason, J.E., Wilson, N.J., Diamond, D.M., Guzowski, J.F. and Morgan, D. (2004) Amyloid suppresses induction of genes critical for memory consolidation in APP + PS1 transgenic mice. J. Neurochem. 88, 434–442.
Donai, H., Sugiura, H., Ara, D., Yoshimura, Y., Yamagata, K. and Yamauchi, T. (2003) Interaction of Arc with CaM kinase II and stimulation of neurite extension by Arc in neuroblastoma cells expressing CaM kinase II. Neurosci. Res. 47, 399–408.
Dynes, J.L. and Steward, O. (2007) Dynamics of bidirectional transport of Arc mRNA in neuronal dendrites. J. Comp. Neurol. 500, 433–447.
Ekstrom, A.D., Meltzer, J., McNaughton, B.L. and Barnes, C.A. (2001) NMDA receptor antagonism blocks experience-dependent expansion of hippocampal “place fields”. Neuron 31, 631–638.
Fletcher, B.R., Calhoun, M.E., Rapp, P.R. and Shapiro, M.L. (2006) Fornix lesions decouple the induction of hippocampal arc transcription from behavior but not plasticity. J. Neurosci. 26, 1507–1515.
Fletcher, B.R., Baxter, M.G., Guzowski, J.F., Shapiro, M.L. and Rapp, P.R. (2007) Selective cholinergic depletion of the hippocampus spares both behaviorally induced Arc transcription and spatial learning and memory. Hippocampus 17, 227–234.
Fujimoto, T., Tanaka, H., Kumamaru, E., Okamura, K. and Miki, N. (2004) Arc interacts with microtubules/microtubule-associated protein 2 and attenuates microtubule-associated protein 2 immunoreactivity in the dendrites. J. Neurosci. Res. 76, 51–63.
Goelet, P., Castellucci, V.F., Schacher, S. and Kandel, E.R. (1986) The long and the short of long-term memory–a molecular framework. Nature 322, 419–422.
Guzowski, J.F. (2002) Insights into immediate-early gene function in hippocampal memory consolidation using antisense oligonucleotide and fluorescent imaging approaches. Hippocampus 12, 86–104.
Guzowski, J.F. (2006) Immediate early genes and the mapping of environmental representations in hippocampal neural networks. In: R. Pinaud, L.A. Tremere, (Eds.), Immediate early genes in sensory processing, cognitive performance, and neurological disorders. Springer, New York, pp. 159–176.
Guzowski, J.F. and McGaugh, J.L. (1997) Interaction of neuromodulatory systems regulating memory storage. In: M. Decker and J.D. Brioni, (Eds.), Alzheimer’s Disease: Molecular Aspects and Pharmacological Treatments. Wiley-Liss. pp 37–61.
Guzowski, J.F., Knierim, J.J. and Moser, E.I. (2004) Ensemble Dynamics of Hippocampal Regions CA3 and CA1. Neuron 44, 581–584.
(0000Guzowski, J.F., McNaughton, B.L., Barnes, C.A. and Worley, P.F. (1999) Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nat. Neurosci. 2, 1120–1124.
Guzowski, J.F., Setlow, B., Wagner, E.K. and McGaugh, J.L. (2001a)Experience-dependent gene expression in the rat hippocampus after spatial learning: A comparison of the immediate-early genes Arc, c-fos, and zif268. J. Neurosci. 21, 5089–5098.
Guzowski, J.F., McNaughton, B.L., Barnes, C.A. and Worley, P.F. (2001b) Imaging neural activity with temporal and cellular resolution using FISH. Curr. Opin. Neurobiol. 11, 579–584.
Guzowski, J.F., Houston, F.P., Worley, P.F. and Barnes, C.A. (2001c) Experience-dependent Arc expression in hippocampal neurons: Role of NMDA receptors and voltage-dependent calcium channels. In: Society for Neuroscience Annual Meeting. San Diego, CA.
Guzowski, J.F., Timlin, J.A., Roysam, B., McNaughton, B.L., Worley, P.F. and Barnes, C.A. (2005) Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr. Opin. Neurobiol. 15, 599–606.
Guzowski, J.F., Lyford, G.L., Stevenson, G.D., Houston, F.P., McGaugh, J.L., Worley, P.F. and Barnes, C.A. (2000) Inhibition of activity-dependent arc protein expression in the rat hippocampus impairs the maintenance of long-term potentiation and the consolidation of long-term memory. J. Neurosci. 20, 3993–4001.
Guzowski, J.F., Miyashita, T., Chawla, M.K., Sanderson, J., Maes, L.I., Houston, F.P., Lipa, P., McNaughton, B.L., Worley, P.F. and Barnes, C.A. (2006) Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons. Proc. Natl. Acad. Sci. USA 103, 1077–1082.
Han, J.H., Kushner, S.A., Yiu, A.P., Cole, C.J., Matynia, A., Brown, R.A., Neve, R.L., Guzowski, J.F., Silva, A.J. and Josselyn, S.A. (2007) Neuronal competition and selection during memory formation. Science 316, 457–460.
Herdegen, T. and Leah, J.D. (1998) Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res. Brain Res. Rev. 28, 370–490.
Husi, H., Ward, M.A., Choudhary, J.S., Blackstock, W.P. and Grant, S.G. (2000) Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nat. Neurosci. 3, 661–669.
Ikegaya, Y., Saito, H. and Abe, K. (1994) Attenuated hippocampal long-term potentiation in basolateral amygdala-lesioned rats. Brain Res. 656, 157–164.
Ikegaya, Y., Saito, H. and Abe, K. (1995) Requirement of basolateral amygdala neuron activity for the induction of long-term potentiation in the dentate gyrus in vivo. Brain Res. 671, 351–354.
Impey, S., McCorkle, S.R., Cha-Molstad, H., Dwyer, J.M., Yochum, G.S., Boss, J.M., McWeeney, S., Dunn, J.J., Mandel, G. and Goodman, R.H. (2004) Defining the CREB regulon: a genome-wide analysis of transcription factor regulatory regions. Cell 119, 1041–1054.
Kang, H., Sun, L.D., Atkins, C.M., Soderling, T.R., Wilson, M.A. and Tonegawa, S. (2001) An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory. Cell 106, 771–783.
Kentros, C., Hargreaves, E., Hawkins, R.D., Kandel, E.R., Shapiro, M. and Muller, R.V. (1998) Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280, 2121–2126.
Lanahan, A. and Worley, P. (1998) Immediate-early genes and synaptic function. Neurobiol. Learn. Mem. 70, 37–43.
Lee, M.G., Chrobak, J.J., Sik, A., Wiley, R.G. and Buzsaki, G. (1994) Hippocampal theta activity following selective lesion of the septal cholinergic system. Neuroscience 62, 1033–1047.
Levenson, J.M., O’Riordan, K.J., Brown, K.D., Trinh, M.A., Molfese, D.L. and Sweatt, J.D. (2004) Regulation of histone acetylation during memory formation in the hippocampus. J. Biol. Chem. 279, 40545–40559.
Limback-Stokin, K., Korzus, E., Nagaoka-Yasuda, R. and Mayford, M. (2004) Nuclear calcium/calmodulin regulates memory consolidation. J. Neurosci. 24, 10858–10867.
Link, W., Konietsko, U., Kauselmann, G., Krug, M., Schwanke, B., Frey, U., Kuhl, D. (1995) Somatodendritic expression of an immediate-early gene is regulated by synaptic activity. Proc. Natl. Acad. Sci. USA 92, 5734–5738.
Lyford, G.L., Yamagata, K., Kaufmann, W.E., Barnes, C.A., Sanders, L.K., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Lanahan, A.A. and Worley, P.F. (1995) Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron 14, 433–445.
Malinow, R. and Malenka, R.C. (2002) AMPA receptor trafficking and synaptic plasticity. Annu. Rev. Neurosci. 25, 103–126.
McGaugh, J.L. (2000) Memory–A Century of Consolidation. Science 287, 248–251.
McIntyre, C.K., Miyashita, T., Setlow, B., Marjon, K.D., Steward, O., Guzowski, J.F. and McGaugh, J.L. (2005) Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus. Proc. Natl. Acad. Sci. USA 102, 10718–10723.
Messaoudi, E., Ying, S.W., Kanhema, T., Croll, S.D. and Bramham, C.R. (2002) Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo. J. Neurosci. 22, 7453–7461.
Moga, D.E., Calhoun, M.E., Chowdhury, A., Worley, P., Morrison, J.H. and Shapiro, M.L. (2004) Activity-regulated cytoskeletal-associated protein is localized to recently activated excitatory synapses. Neuroscience 125, 7–11.
Mokin, M., Lindahl, J.S. and Keifer, J. (2006) Immediate-early gene-encodedprotein Arc is associated with synaptic delivery of GluR4-containing AMPA receptors during in vitro classical conditioning. J. Neurophysiol. 95, 215–224.
Petrovich, G.D., Holland, P.C. and Gallagher, M. (2005) Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating. J. Neurosci. 25, 8295–8302.
Plath, N., Ohana, O., Dammermann, B., Errington, M.L., Schmitz, D., Gross, C., Mao, X., Engelsberg, A., Mahlke, C., Welzl, H., Kobalz, U., Stawrakakis, A., Fernandez, E., Waltereit, R., Bick-Sander, A., Therstappen, E., Cooke, S.F., Blanquet, V., Wurst, W., Salmen, B., Bosl, M.R., Lipp, H.P., Grant, S.G., Bliss, T.V., Wolfer, D.P. and Kuhl, D. (2006) Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52, 437–444.
Ramanan, N., Shen, Y., Sarsfield, S., Lemberger, T., Schutz, G., Linden, D.J. and Ginty, D.D. (2005) SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability. Nat. Neurosci. 8, 759–767.
Ramirez-Amaya, V., Vazdarjanova, A., Mikhael, D., Rosi, S., Worley, P.F. and Barnes, C.A. (2005) Spatial exploration-induced Arc mRNA and protein expression: evidence for selective, network-specific reactivation. J. Neurosci. 25, 1761–1768.
Rial Verde, E.M., Lee-Osbourne, J., Worley, P.F., Malinow, R. and Cline, H.T. (2006) Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron 52, 461–474.
Robertson, L.M., Kerppola, T.K., Vendrell, M., Luk, D., Smeyne, R.J., Bocchiaro, C., Morgan, J.I. and Curran, T. (1995) Regulation of c-fos expression in transgenic mice requires multiple interdependent transcription control elements. Neuron 14, 241–252.
Shepherd, J.D., Rumbaugh, G., Wu, J., Chowdhury, S., Plath, N., Kuhl, D., Huganir, R.L. and Worley, P.F. (2006) Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron 52, 475–484.
Steward, O. and Levy, W.B. (1982) Preferential localization of polyribosomes under the base of dendritic spines in granule cells of the dentate gyrus. J. Neurosci. 2, 284–291.
Steward, O. and Schuman, E.M. (2001) Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 299–325.
Steward, O. and Worley, P.F. (2001) Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation. Neuron 30, 227–240.
Steward, O. and Worley, P. (2002) Local synthesis of proteins at synaptic sites on dendrites: role in synaptic plasticity and memory consolidation? Neurobiol. Learn. Mem. 78, 508–527.
Steward, O., Wallace, C.S., Lyford, G.L. and Worley, P.F. (1998) Synaptic activation causes the mRNA for the IEG Arc to localize selectively near activated postsynaptic sites on dendrites. Neuron 21, 741–751.
Tzingounis, A.V. and Nicoll, R.A. (2006) Arc/Arg3.1: linking gene expression to synaptic plasticity and memory. Neuron 52, 403–407.
Vazdarjanova, A. and Guzowski, J.F. (2004) Differences in hippocampal neuronal population responses to modifications of an environmental context: evidence for distinct, yet complementary, functions of CA3 and CA1 ensembles. J. Neurosci. 24, 6489–6496.
Vazdarjanova, A., McNaughton, B.L., Barnes, C.A., Worley, P.F. and Guzowski, J.F. (2002) Experience-dependent coincident expression of the effector immediate-early genes Arc and Homer 1a in hippocampal and neocortical neuronal networks. J. Neurosci. 22, 10067–10071.
Vazdarjanova, A., Ramirez-Amaya, V., Insel, N., Worley, P.F., Guzowski, J.F. and Barnes, C.A. (2004) Behavior induces expression of the plasticity-related immediate-early gene Arc in excitatory and inhibitory CaMKII - positive neurons. In: Society for Neuroscience 34th Annual Meeting. San Diego, CA.
Vazdarjanova, A., Ramirez-Amaya, V., Insel, N., Plummer, T.K., Rosi, S., Chowdhury, S., Mikhael, D., Worley, P.F., Guzowski, J.F. and Barnes, C.A. (2006) Spatial exploration induces ARC, a plasticity-related immediate-early gene, only in calcium/calmodulin-dependent protein kinase II-positive principal excitatory and inhibitory neurons of the rat forebrain. J. Comp. Neurol. 498, 317–329.
Wallace, C.S., Lyford, G.L., Worley, P.F. and Steward, O. (1998) Differential intracellular sorting of immediate early gene mRNAs depends on signals in the mRNA sequence. J. Neurosci. 18, 26–35.
Waltereit, R., Dammermann, B., Wulff, P., Scafidi, J., Staubli, U., Kauselmann, G., Bundman, M. and Kuhl, D. (2001) Arg3.1/Arc mRNA induction by Ca2+ and cAMP requires protein kinase A and mitogen-activated protein kinase/extracellular regulated kinase activation. J. Neurosci. 21, 5484–5493.
Xia, Z., Dudek, H., Miranti, C.K. and Greenberg, M.E. (1996) Calcium influx via the NMDA receptor induces immediate early gene transcription by a MAP kinase/ERK-dependent mechanism. J. Neurosci. 16, 5425–5436.
Yin, Y., Edelman, G.M. and Vanderklish, P.W. (2002) The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes. Proc. Natl. Acad. Sci. USA 99, 2368–2373.
Ying, S.W., Futter, M., Rosenblum, K., Webber, M.J., Hunt, S.P., Bliss, T.V. and Bramham, C.R. (2002) Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis. J. Neurosci. 22, 1532–1540.
Zhang, W.P., Guzowski, J.F. and Thomas, S.A. (2005) Mapping neuronal activation and the influence of adrenergic signaling during contextual memory retrieval. Learn. Mem. 12, 239–247.
Zou, Z. and Buck, L.B. (2006) Combinatorial effects of odorant mixes in olfactory cortex. Science 311, 1477–1481.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Guzowski, J.F., Nie, T., Miyashita, T. (2008). Dynamic Transcription of the Immediate-Early Gene Arc in Hippocampal Neuronal Networks: Insights into the Molecular and Cellular Bases of Memory Formation. In: Dudek, S.M. (eds) Transcriptional Regulation by Neuronal Activity. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-73609-9_19
Download citation
DOI: https://doi.org/10.1007/978-0-387-73609-9_19
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-73608-2
Online ISBN: 978-0-387-73609-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)