Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

McNulty, Susan E.; Barrett, Ruth M.; Vogel-Ciernia, Annie; Malvaez, Melissa; Hernandez, Nicole; Davatolhagh, M. Felicia; Matheos, Dina P.; Schiffman, Aaron; Wood, Marcelo A.

doi:10.1101/lm.026385.112

PreprintCited by 117Memory and Neural MechanismsMemory Processes and InfluencesNeuroscience and Neuropharmacology Research

Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

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McNulty, Susan E., Barrett, Ruth M., Vogel-Ciernia, Annie, Malvaez, Melissa, Hernandez, Nicole, Davatolhagh, M. Felicia, Matheos, Dina P., Schiffman, Aaron +1 more·2012·Learning & Memory

DOI 10.1101/lm.026385.112PMC PMC3506974

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Abstract

Nr4a1 and Nr4a2 are transcription factors and immediate early genes belonging to the nuclear receptor Nr4a family. In this study, we examine their role in long-term memory formation for object location and object recognition. Using siRNA to block expression of either Nr4a1 or Nr4a2, we found that Nr4a2 is necessary for both long-term memory for object location and object recognition. In contrast, Nr4a1 appears to be necessary only for object location. Indeed, their roles in these different types of long-term memory may be dependent on their expression in the brain, as NR4A2 was found to be expressed in hippocampal neurons (associated with object location memory) as well as in the insular and perirhinal cortex (associated with object recognition memory), whereas NR4A1 showed minimal neuronal expression in these cortical areas. These results begin to elucidate how NR4A1 and NR4A2 differentially contribute to object location versus object recognition memory.

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Object exploration increased expression of the immediate-early genes Nr4a1 and Nr4a2, while intra-hippocampal knockdown of either one impaired long-term OPP (24 hours) memory.
“Object exploration also increased the expression of the immediate-early genes Nr4a1 and Nr4a2, while intra-hippocampal knockdown of either one impaired long-term OPP (24 hours) memory”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as McNulty et al., 2012

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Bourtchuladze, R., Frenguelli, B., Blendy, J., Cioffi, D., Schutz, G., & Silva, A. J. (1994) · Cell · doi:10.1016/0092-8674(94)90400-6 · Cited by 1,800 · see citing works
Transcription Factors in Long-Term Memory and Synaptic Plasticity
Alberini, C. M. (2009) · Physiological Reviews · doi:10.1152/physrev.00017.2008 · Cited by 991 · see citing works
Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila
Yin, J. C. P., Wallach, J. S., Del Vecchio, M., Wilder, E. L., Zhou, H., Quinn, W. G., & Tully, T. (1994) · Cell · doi:10.1016/0092-8674(94)90399-9 · Cited by 959 · see citing works
Histone Deacetylase Inhibitors Enhance Memory and Synaptic Plasticity via CREB: CBP-Dependent Transcriptional Activation
Vecsey, C. G., Hawk, J. D., Lattal, K. M., Stein, J. M., Fabian, S., Attner, M. A., Cabrera, S. M., McDonough, C. B., Brindle, P. K., Abel, T. G., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0296-07.2007 · Cited by 828 · see citing works
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Barker, G. R. I., & Warburton, E. C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6413-10.2011 · Cited by 818 · see citing works
Contextual fear, gestalt memories, and the hippocampus.
Fanselow, M. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00186-2 · Cited by 724 · see citing works
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McQuown, S. C., Barrett, R. M., Matheos, D. P., Post, R. J., Rogge, G. A., Alenghat, T., Mullican, S. E., Jones, S., Rusche, J. R., Lazar, M. A., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5052-10.2011 · Cited by 507 · see citing works
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Guzowski, J. F., & McGaugh, J. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.6.2693 · Cited by 481 · see citing works
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Pittenger, C., Huang, Y. Y., Paletzki, R. F., Bourtchouladze, R., Scanlin, H., Vronskaya, S., & Kandel, E. R. (2002) · Neuron · doi:10.1016/s0896-6273(02)00684-0 · Cited by 464 · see citing works
Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system
Zetterström, R. H., Williams, R., Perlmann, T., & Olson, L. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(96)00074-5 · Cited by 340 · see citing works
A comparison of two immediate-early genes, c-fos and NGFI-B, as markers for functional activation in stress-related neuroendocrine circuitry
Chan, R., Brown, E., Ericsson, A., Kovacs, K., & Sawchenko, P. (1993) · The Journal of Neuroscience · doi:10.1523/jneurosci.13-12-05126.1993 · Cited by 289 · see citing works
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Maren, S., & Holt, W. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(99)00188-6 · Cited by 256 · see citing works
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Baker, K. D., Shewchuk, L. M., Kozlova, T., Makishima, M., Hassell, A. M., Wisely, B., Caravella, J. A., Lambert, M. H., Reinking, J. L., Krause, H. M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00420-3 · Cited by 238 · see citing works
Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification
Roozendaal, B., Hernandez, A., Cabrera, S. M., Hagewoud, R., Malvaez, M., Stefanko, D. P., Haettig, J., & Wood, M. A. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5717-09.2010 · Cited by 233 · see citing works
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Balschun, D., Wolfer, D. P., Gass, P., Mantamadiotis, T., Welzl, H., Schütz, G., Frey, J. U., & Lipp, H.-P. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06304.2003 · Cited by 229 · see citing works
The consolidation of object and context recognition memory involve different regions of the temporal lobe
Balderas, I., Rodriguez-Ortiz, C. J., Salgado-Tonda, P., Chavez-Hurtado, J., McGaugh, J. L., & Bermudez-Rattoni, F. (2008) · Learning & Memory · doi:10.1101/lm.1028008 · Cited by 213 · see citing works
HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner
Haettig, J., Stefanko, D. P., Multani, M. L., Figueroa, D. X., McQuown, S. C., & Wood, M. A. (2011) · Learning & Memory · doi:10.1101/lm.1986911 · Cited by 211 · see citing works
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von Hertzen, L. S. J., & Giese, K.-P. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4707-04.2005 · Cited by 185 · see citing works
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Fass, D. M., Butler, J. E. F., & Goodman, R. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305905200 · Cited by 136 · see citing works
The role of NR4A transcription factors in memory formation
Hawk, J. D., & Abel, T. G. (2011) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.02.001 · Cited by 128 · see citing works
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Xiao, Q., Castillo, S. O., & Nikodem, V. M. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00159-5 · Cited by 114 · see citing works
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Cárdenas, O. S., & Conneely, O. M. (1996) · Journal of Molecular Neuroscience · doi:10.1007/bf02736848 · Cited by 106 · see citing works
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O'Keefe, J. M., & Burgess, N. (1999) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(99)01396-0 · Cited by 95 · see citing works
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de Ortı́z, S. P., Maldonado-Vlaar, C. S., & Carrasquillo, Y. (2000) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1999.3952 · Cited by 83 · see citing works
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Colón, W. I., Martínez, M., Morales, S., Félix, J., Cruz, J., Adorno, M., Pereira, L., Colón, N., Maldonado-Vlaar, C. S., & de Ortı́z, S. P. (2006) · Learning & Memory · doi:10.1101/lm.407706 · Cited by 81 · see citing works
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Honkaniemi, J., Sagar, S. M., Pyykönen, I., Hicks, K. J., & Sharp, F. R. (1995) · Molecular Brain Research · doi:10.1016/0169-328x(94)00200-x · Cited by 58 · see citing works
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Keeley, M. B., Wood, M. A., Isiegas, C., Stein, J. M., Hellman, K. M., Hannenhalli, S. S., & Abel, T. G. (2006) · Learning & Memory · doi:10.1101/lm.86906 · Cited by 58 · see citing works
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Induction of NGFI-B mRNA following contextual fear conditioning and its blockade by diazepam
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Alpha-isoform of Ca2+/calmodulin-dependent kinase II autophosphorylation is required for memory consolidation-specific transcription
von Hertzen, L. S. J., & Giese, K.-P. (2005) · Neuroreport · doi:10.1097/01.wnr.0000175244.51084.bb · Cited by 33 · see citing works
Generation of Dopamine Neurons with Improved Cell Survival and Phenotype Maintenance Using a Degradation-Resistant Nurr1 Mutant
Jo, A.-Y., Kim, M.-Y., Lee, H., Rhee, Y., Lee, J. E., Baek, K., Park, C., Koh, H.-C., Shin, I., Lee, Y., et al. (2009) · Stem Cells · doi:10.1002/stem.146 · Cited by 29 · see citing works

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Authors: McNulty, S. E., Barrett, R. M., Vogel-Ciernia, A., Malvaez, M., Hernandez, N., Davatolhagh, M. F., Matheos, D. P., Schiffman, A., & Wood, M. A.
Affiliations: University of California, Irvine (US)
ORCID: Malvaez, Melissa
Davatolhagh, M. Felicia
Matheos, Dina P.
Wood, Marcelo A.
Venue: Learning & Memory
Publisher: Cold Spring Harbor Laboratory
Published: 2012-11-16
Volume: 19
Issue: 12
Pages: 588-592
ISSN: 1072-0502 (ISSN-L)
1549-5485
DOI: 10.1101/lm.026385.112
PMC: PMC3506974
OpenAlex: W2021409596
Cited by: 117
References: 35
Citations by year: 2026: 1 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 8 · 2019: 11 · 2018: 12 · 2017: 7 · 2016: 12 · 2015: 3 · 2014: 10 · 2013: 7
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Learning & Memory (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: National Institutes of Health (DA025922)
National Institute of Mental Health (DA025922, R01MH081004, MH081004, MH081004-02S1, F31MH85494, F31MH085494)
National Institute on Drug Abuse (R21DA031989, R01DA025922, DA 025922, F31DA29368, F31DA029368, DA031989, T32DA028874)
National Institute of General Medical Sciences (GM 55246, R25GM055246)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Nur77, Nurr1, object location memory, object recognition memory, long-term memory formation, hippocampal neurons, insula, perirhinal cortex, transcription factors, immediate early genes, siRNA knockdown
MeSH terms: Animals, Cerebral Cortex, Gene Expression Regulation, Hippocampus, Learning, Male, Mice, Inbred C57BL, Neurons, Phosphopyruvate Hydratase, RNA, Messenger, Time Factors, Recognition, Psychology, RNA, Small Interfering, Mice, Nuclear Receptor Subfamily 4, Group A, Member 1, Nuclear Receptor Subfamily 4, Group A, Member 2, Memory, Long-Term

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Differential roles for Nr4a1 and Nr4a2 in object location vs. object recognition long-term memory

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