The novel object recognition memory: neurobiology, test procedure, and its modifications.

doi:10.1007/S10339-011-0430-Z

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The novel object recognition memory: neurobiology, test procedure, and its modifications.

Journal Article•DOI•

The novel object recognition memory: neurobiology, test procedure, and its modifications.

Marta Coelho Antunes¹, Marta Coelho Antunes², Grazyna Biala¹•Institutions (2)

Medical University of Lublin¹, University of Lisbon²

01 May 2012-Cognitive Processing (Springer-Verlag)-Vol. 13, Iss: 2, pp 93-110

TL;DR: The neurobiology and methodological modifications of the test commonly used in behavioral pharmacology are reviewed to review the novel object recognition paradigms in animals, as a valuable measure of cognition.

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Abstract: Animal models of memory have been considered as the subject of many scientific publications at least since the beginning of the twentieth century. In humans, memory is often accessed through spoken or written language, while in animals, cognitive functions must be accessed through different kind of behaviors in many specific, experimental models of memory and learning. Among them, the novel object recognition test can be evaluated by the differences in the exploration time of novel and familiar objects. Its application is not limited to a field of research and enables that various issues can be studied, such as the memory and learning, the preference for novelty, the influence of different brain regions in the process of recognition, and even the study of different drugs and their effects. This paper describes the novel object recognition paradigms in animals, as a valuable measure of cognition. The purpose of this work was to review the neurobiology and methodological modifications of the test commonly used in behavioral pharmacology.

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Journal Article•DOI•

Cognitive impairment by antibiotic-induced gut dysbiosis: Analysis of gut microbiota-brain communication

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Esther E. Fröhlich¹, Aitak Farzi¹, Raphaela Mayerhofer¹, Florian Reichmann¹, Angela Jačan¹, Bernhard Wagner², Erwin Zinser², Natalie Bordag, Christoph Magnes³, Eleonore Fröhlich¹, Karl Kashofer¹, Gregor Gorkiewicz¹, Peter Holzer¹ - Show less +9 more•Institutions (3)

Medical University of Graz¹, FH Joanneum², Joanneum Research³

01 Aug 2016-Brain Behavior and Immunity

TL;DR: In this paper, the effect of intragastric treatment of adult mice with multiple antibiotics on the gut microbial community, metabolite profile in the colon, circulating metabolites, expression of neuronal signaling molecules in distinct brain areas and cognitive behavior is systematically investigated.

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Abstract: Emerging evidence indicates that disruption of the gut microbial community (dysbiosis) impairs mental health. Germ-free mice and antibiotic-induced gut dysbiosis are two approaches to establish causality in gut microbiota-brain relationships. However, both models have limitations, as germ-free mice display alterations in blood-brain barrier and brain ultrastructure and antibiotics may act directly on the brain. We hypothesized that the concerns related to antibiotic-induced gut dysbiosis can only adequately be addressed if the effect of intragastric treatment of adult mice with multiple antibiotics on (i) gut microbial community, (ii) metabolite profile in the colon, (iii) circulating metabolites, (iv) expression of neuronal signaling molecules in distinct brain areas and (v) cognitive behavior is systematically investigated. Of the antibiotics used (ampicillin, bacitracin, meropenem, neomycin, vancomycin), ampicillin had some oral bioavailability but did not enter the brain. 16S rDNA sequencing confirmed antibiotic-induced microbial community disruption, and metabolomics revealed that gut dysbiosis was associated with depletion of bacteria-derived metabolites in the colon and alterations of lipid species and converted microbe-derived molecules in the plasma. Importantly, novel object recognition, but not spatial, memory was impaired in antibiotic-treated mice. This cognitive deficit was associated with brain region-specific changes in the expression of cognition-relevant signaling molecules, notably brain-derived neurotrophic factor, N-methyl-d-aspartate receptor subunit 2B, serotonin transporter and neuropeptide Y system. We conclude that circulating metabolites and the cerebral neuropeptide Y system play an important role in the cognitive impairment and dysregulation of cerebral signaling molecules due to antibiotic-induced gut dysbiosis.

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485 citations

Cites background from "The novel object recognition memory..."

...…by gut dysbiosis we focused on the medial prefrontal cortex, hippocampus and amygdala, all of which make distinct contributions to object recognition (Moses et al., 2005; Balderas et al., 2008; Broadbent et al., 2009; Barker and Warburton, 2011; Antunes and Biala, 2012; Beldjoud et al., 2015)....
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Journal Article•DOI•

Causal evidence for the role of REM sleep theta rhythm in contextual memory consolidation.

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Richard Boyce¹, Stephen D. Glasgow¹, Sylvain Williams¹, Antoine Roger Adamantidis², Antoine Roger Adamantidis¹ - Show less +1 more•Institutions (2)

McGill University¹, University of Bern²

13 May 2016-Science

TL;DR: It is demonstrated that MSGABA neuronal activity specifically during REMS is required for normal memory consolidation, and optogenetically silenced medial septum γ-aminobutyric acid–releasing (MSGABA) neurons selectively during a REMS critical window after learning erased subsequent novel object place recognition and impaired fear-conditioned contextual memory.

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Abstract: Rapid eye movement sleep (REMS) has been linked with spatial and emotional memory consolidation. However, establishing direct causality between neural activity during REMS and memory consolidation has proven difficult because of the transient nature of REMS and significant caveats associated with REMS deprivation techniques. In mice, we optogenetically silenced medial septum γ-aminobutyric acid-releasing (MS(GABA)) neurons, allowing for temporally precise attenuation of the memory-associated theta rhythm during REMS without disturbing sleeping behavior. REMS-specific optogenetic silencing of MS(GABA) neurons selectively during a REMS critical window after learning erased subsequent novel object place recognition and impaired fear-conditioned contextual memory. Silencing MS(GABA) neurons for similar durations outside REMS episodes had no effect on memory. These results demonstrate that MS(GABA) neuronal activity specifically during REMS is required for normal memory consolidation.

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474 citations

Journal Article•DOI•

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice.

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Lindsay M. Lueptow¹•Institutions (1)

Icahn School of Medicine at Mount Sinai¹

30 Aug 2017-Journal of Visualized Experiments

TL;DR: The object recognition test is a relatively low-stress, efficient test for memory in mice, and is appropriate for the detection of neuropsychological changes following pharmacological, biological, or genetic manipulations.

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Abstract: The object recognition test (ORT) is a commonly used behavioral assay for the investigation of various aspects of learning and memory in mice. The ORT is fairly simple and can be completed over 3 days: habituation day, training day, and testing day. During training, the mouse is allowed to explore 2 identical objects. On test day, one of the training objects is replaced with a novel object. Because mice have an innate preference for novelty, if the mouse recognizes the familiar object, it will spend most of its time at the novel object. Due to this innate preference, there is no need for positive or negative reinforcement or long training schedules. Additionally, the ORT can also be modified for numerous applications. The retention interval can be shortened to examine short-term memory, or lengthened to probe long-term memory. Pharmacological intervention can be used at various times prior to training, after training, or prior to recall to investigate different phases of learning (i.e., acquisition, early or late consolidation, or recall). Overall, the ORT is a relatively low-stress, efficient test for memory in mice, and is appropriate for the detection of neuropsychological changes following pharmacological, biological, or genetic manipulations.

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455 citations

Journal Article•DOI•

Irradiation in a flash: Unique sparing of memory in mice after whole brain irradiation with dose rates above 100 Gy/s

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Pierre Montay-Gruel¹, Pierre Montay-Gruel², Kristoffer Petersson¹, Maud Jaccard¹, Gael Boivin¹, Jean-François Germond¹, Benoit Petit¹, Raphael Doenlen³, Vincent Favaudon², François Bochud¹, Claude Bailat¹, Jean Bourhis¹, Marie-Catherine Vozenin¹ - Show less +9 more•Institutions (3)

University of Lausanne¹, Université Paris-Saclay², École Polytechnique Fédérale de Lausanne³

22 May 2017-Radiotherapy and Oncology

TL;DR: This study shows for the first time that normal brain tissue toxicities after WBI can be reduced with increased dose rate.

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363 citations

Cites methods from "The novel object recognition memory..."

...Dose rate effect on neuroprotection was evaluated by ‘‘Novel Object Recognition test” [18], performed on the mice two months post-irradiation, as described by Acharya et al....
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...These cognitive impairments can be evaluated using the ‘‘Novel Object Recognition test” [18] on WBI murine models [19]....
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Journal Article•DOI•

Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice

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Nabil N. Dagher¹, Allison R. Najafi¹, Kara M. Neely Kayala¹, Monica R. P. Elmore¹, Terra E. White¹, Rodrigo Medeiros¹, Brian L. West², Kim N. Green¹ - Show less +4 more•Institutions (2)

University of California, Irvine¹, Plexxikon²

01 Aug 2015-Journal of Neuroinflammation

TL;DR: Inhibition of the CSF1R at lower levels in 3xTg-AD mice prevents microglial association with plaques and improves cognition, and sustained microglia elimination is concentration-dependent.

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Abstract: Microglia are dependent upon colony-stimulating factor 1 receptor (CSF1R) signaling for their survival in the adult brain, with administration of the dual CSF1R/c-kit inhibitor PLX3397 leading to the near-complete elimination of all microglia brainwide. Here, we determined the dose-dependent effects of a specific CSF1R inhibitor (PLX5622) on microglia in both wild-type and the 3xTg-AD mouse model of Alzheimer’s disease. Wild-type mice were treated with PLX5622 for up to 21 days, and the effects on microglial numbers were assessed. 3xTg-AD mice were treated with PLX5622 for 6 or 12 weeks and effects on microglial numbers and pathology subsequently assessed. High doses of CSF1R inhibitor eliminate most microglia from the brain, but a 75 % lower-dose results in sustained elimination of ~30 % of microglia in both wild-type and 3xTg-AD mice. No behavioral or cognitive deficits were found in mice either depleted of microglia or treated with lower CSF1R inhibitor concentrations. Aged 3xTg-AD mice treated for 6 or 12 weeks with lower levels of PLX5622 resulted in improved learning and memory. Aβ levels and plaque loads were not altered, but microglia in treated mice no longer associated with plaques, revealing a role for the CSF1R in the microglial reaction to plaques, as well as in mediating cognitive deficits. We find that inhibition of CSF1R alone is sufficient to eliminate microglia and that sustained microglial elimination is concentration-dependent. Inhibition of the CSF1R at lower levels in 3xTg-AD mice prevents microglial association with plaques and improves cognition.

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357 citations

Cites methods from "The novel object recognition memory..."

...3xTg-AD mice treated for 6 weeks were tested on novel place and novel object recognition, tasks that test hippocampal- and corticaldependent memory, respectively, that rely on a rodent’s preference to explore a novel object or object location over the familiar one [23]....
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References

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Journal Article•DOI•

A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data.

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Abdelkader Ennaceur¹, Jean Delacour¹•Institutions (1)

University of Paris¹

01 Nov 1988-Behavioural Brain Research

TL;DR: A new memory test in rats, based on the differential exploration of familiar and new objects, which is comparable to memory tests currently used in man and allows interspecies comparisons.

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2,970 citations

"The novel object recognition memory..." refers background or methods in this paper

...It can be calculated through different indexes, as discrimination index, index of global habituation, or preference index depending on the aim of each study (Ennaceur and Delacour 1988; Gaskin et al. 2010; Hammond et al. 2004)....
[...]
...According to Ennaceur and Delacour (1988), when the global amnesic syndromes are analyzed, at least two types of memory could be distinguished....
[...]
...Ennaceur and Delacour (1988) used an open box made of wood 65 9 45 9 65 cm....
[...]
...Some differences were observed in light condition; although tests were made with constant illumination, its intensity varied, and it can range from \10 lux (Silvers et al. 2007) to 30–40 lux (Clarke et al. 2010; Ennaceur and Delacour 1988; Weible et al. 2009)....
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...However, it M. Antunes G. Biala (&) Chair and Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4A Chodźki St, 20-093 Lublin, Poland e-mail: grazyna.biala@umlub.pl M. Antunes e-mail: martacoelhoantunes@gmail.com...
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Journal Article•DOI•

A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory

[...]

Abdelkader Ennaceur¹, Kamel Meliani•Institutions (1)

University of Paris¹

31 Oct 1992-Behavioural Brain Research

TL;DR: There is no correlation between the three tests which argues for a multiple form of working memory, especially a spatial and a non-spatial one, and the level of discrimination in the spatial recognition test was significantly reduced compared to that of control.

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1,097 citations

"The novel object recognition memory..." refers background or methods in this paper

...1 day, with different duration and number of sessions 3 or 5 min (Ennaceur and Delacour 1988), 3 min (Aubele et al. 2008; Ennaceur and Delacour 1988; Reger et al. 2009; Nanfaro et al. 2010; Walf et al. 2009), 4 min (Burke et al....
[...]
...It can be calculated through different indexes, as discrimination index, index of global habituation, or preference index depending on the aim of each study (Ennaceur and Delacour 1988; Gaskin et al. 2010; Hammond et al. 2004)....
[...]
...According to Ennaceur and Delacour (1988), when the global amnesic syndromes are analyzed, at least two types of memory could be distinguished....
[...]
...Ennaceur and Delacour (1988) used an open box made of wood 65 9 45 9 65 cm....
[...]
...Some differences were observed in light condition; although tests were made with constant illumination, its intensity varied, and it can range from \10 lux (Silvers et al. 2007) to 30–40 lux (Clarke et al. 2010; Ennaceur and Delacour 1988; Weible et al. 2009)....
[...]

Journal Article•DOI•

Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice.

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Claire Rampon¹, Ya-Ping Tang², Joe Goodhouse², Eiji Shimizu², Maureen Kyin², Joe Z. Tsien² - Show less +2 more•Institutions (2)

University of Washington¹, Princeton University²

01 Mar 2000-Nature Neuroscience

TL;DR: It is found that enrichment induced an increase of the synapse density in the CA1 region in knockouts as well as control littermates, which indicates that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes.

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Abstract: We produced CA1-specific NMDA receptor 1 subunit-knockout (CA1-KO) mice to determine the NMDA receptor dependence of nonspatial memory formation and of experience-induced structural plasticity in the CA1 region. CA1-KO mice were profoundly impaired in object recognition, olfactory discrimination and contextual fear memories. Surprisingly, these deficits could be rescued by enriching experience. Using stereological electron microscopy, we found that enrichment induced an increase of the synapse density in the CA1 region in knockouts as well as control littermates. Therefore, our data indicate that CA1 NMDA receptor activity is critical in hippocampus-dependent nonspatial memory, but is not essential for experience-induced synaptic structural changes.

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730 citations

Journal Article•DOI•

Impaired Recognition Memory in Rats after Damage to the Hippocampus

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Robert E. Clark¹, Stuart M. Zola¹, Stuart M. Zola², Larry R. Squire², Larry R. Squire¹ - Show less +1 more•Institutions (2)

Veterans Health Administration¹, University of California, San Diego²

01 Dec 2000-The Journal of Neuroscience

TL;DR: The results show that the hippocampus is essential for normal recognition memory and fornix lesions need not mimic the effects of direct damage to hippocampal tissue.

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Abstract: Rats with radio-frequency or ibotenic acid lesions of the hippocampus and rats with radio-frequency lesions of the fornix were tested on the visual paired comparison task (VPC), a test of recognition memory. Memory was assessed at five different delay intervals ranging from 10 sec to 24 hr. All operated groups performed normally at the shorter delays (10 sec and 1 min). Across longer delays, the two groups with hippocampal damage were impaired. Rats with fornix lesions performed well on the VPC task but were impaired on a spatial task (spontaneous alternation). The results show that the hippocampus is essential for normal recognition memory. Moreover, fornix lesions need not mimic the effects of direct damage to hippocampal tissue. The findings are discussed in the context of the contribution of the hippocampus to recognition memory.

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718 citations

"The novel object recognition memory..." refers background or methods in this paper

...Thus, both Nanfaro et al. (2010) and Clark et al. (2000) used 25- and 60-...
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...…Broadbent et al. 2010; Hammond et al. 2004; Goulart et al. 2010; Reger et al. 2009), others used 70–75% (Aubele et al. 2008; Burke et al. 2010; Clarke et al. 2010; Dere et al. 2005; Hale and Good 2005; Gaskin et al. 2010; Sarkisyan and Hedlund 2009) or 95% ethanol solution (Clark et al. 2000)....
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...…that each one considered as exploration, basically within 1–4 cm (Aggleton et al. 2010; Botton et al. 2010; Broadbent et al. 2010; Burke et al. 2010; Clark et al. 2000; Ennaceur and Delacour 1988; Gaskin et al. 2010; Hale and Good 2005; Mumby et al. 2002; Nanfaro et al. 2010; Piterkin et al. 2008;…...
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...Moreover, results of the NOR paradigm are influenced by both hippocampal and cortical lesions (Buckmaster et al. 2004; Clark et al. 2000)....
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...The objects can be made of metal, glass, porcelain, glazed ceramic, rubber, durable nontoxic plastic, aluminum, or wood (Benice and Raber 2008; Broadbent et al. 2010; Burke et al. 2010; Clark et al. 2000; Ennaceur and Delacour 1988; Goulart et al. 2010; Hale and Good 2005; Oliveira et al. 2010; Piterkin et al. 2008; Reger et al. 2009; Mumby et al. 2002; Sarkisyan and Hedlund 2009; Schindler et al. 2010; Walf et al. 2009), i....
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Journal Article•DOI•

Recognition Memory for Objects, Place, and Temporal Order: A Disconnection Analysis of the Role of the Medial Prefrontal Cortex and Perirhinal Cortex

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Gareth R.I. Barker¹, Flora Bird, Victoria Alexander, E. Clea Warburton¹•Institutions (1)

University of Bristol¹

14 Mar 2007-The Journal of Neuroscience

TL;DR: Examination of the role of the medial prefrontal cortex (mPFC) and perirhinal cortex (PRH) in recognition memory processes demonstrates that the mPFC and PRH are crucial for object-in-place associational and recency discriminations, whereas the PRH but not the mFFC is important for the discrimination of novel and familiar individual objects.

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Abstract: Recognition memory requires judgments of the previous occurrence of stimuli made on the basis of the relative familiarity of individual objects, or by integrating information concerning objects and location, or by using recency information. The present study examined the role of the medial prefrontal cortex (mPFC) and perirhinal cortex (PRH) in these distinct recognition memory processes using a series of behavioral tests: a novel object preference task, an object-in-place task, and a temporal order memory task. Also, a disconnection procedure was used to test whether these regions form components of an integrated system for recognition memory. Male DA rats received bilateral lesions in the PRH or mPFC or unilateral lesions placed in both cortices in either the same (PRH-mPFC IPSI) or contralateral (PRH-mPFC CONTRA) hemispheres. A fifth group underwent sham surgery (SHAM). In the object-in-place and temporal order memory tasks, the PRH, mPFC, and PRH-mPFC CONTRA groups were significantly impaired. However, performance in the novel object preference task was only impaired in the PRH group. No group was impaired in the object location task. These results demonstrate that the mPFC and PRH are crucial for object-in-place associational and recency discriminations, whereas the PRH but not the mPFC is important for the discrimination of novel and familiar individual objects. Importantly, these results provide direct support for the hypothesis that to make discriminations based on associational or recency information, both cortical regions operate within an integrated neural network for recognition memory.

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589 citations

"The novel object recognition memory..." refers background in this paper

..., animals spent equal amount of time on both objects because they are both recognized as familiar or because they are both explored as novel (Barker et al. 2007)....
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...…to evaluate the novelty, as a lack of discrimination between novel and familiar objects can be interpreted in two opposite ways, i.e., animals spent equal amount of time on both objects because they are both recognized as familiar or because they are both explored as novel (Barker et al. 2007)....
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