-
ORIGINAL INVESTIGATION
New automated procedure to assess context recognitionmemory in
mice
David Reiss & Ondine Walter & Lucie Bourgoin
&Brigitte L. Kieffer & Abdel-Mouttalib Ouagazzal
Received: 18 October 2013 /Accepted: 6 April 2014 /Published
online: 27 April 2014# Springer-Verlag Berlin Heidelberg 2014
AbstractRationale and objectives Recognition memory is an
impor-tant aspect of human declarative memory and is one of
theroutine memory abilities altered in patients with
amnesticsyndrome and Alzheimers disease. In rodents,
recognitionmemory has been most widely assessed using the novel
objectpreference paradigm, which exploits the spontaneous
prefer-ence that animals display for novel objects. Here, we
usednose-poke units instead of objects to design a simple
automat-ed method for assessing context recognition memory in
mice.Methods In the acquisition trial, mice are exposed for the
firsttime to an operant chamber with one blinking nose-poke unit.In
the choice session, a novel nonblinking nose-poke unit isinserted
into an empty spatial location and the number of nose
poking dedicated to each set of nose-poke unit is used as
anindex of recognition memory.Results We report that recognition
performance varies as afunction of the length of the acquisition
period and the reten-tion delay and is sensitive to conventional
amnestic treat-ments. By manipulating the features of the operant
chamberduring a brief retrieval episode (3-min long), we further
dem-onstrate that reconsolidation of the original contextual
mem-ory depends on the magnitude and the type of
environmentalchanges introduced into the familiar spatial
environment.Conclusions These results show that the nose-poke
recogni-tion task provides a rapid and reliable way for
assessingcontext recognition memory in mice and offers new
possibil-ities for the deciphering of the brain mechanisms
governingthe reconsolidation process.
Keywords Recognitionmemory . Nose-poke units . Spatialcontext .
Consolidation . Reconsolidation .Mice
Introduction
Recognition memory is the ability to judge that a
currentlypresent object, person, place, or event has previously
beenencountered or experienced. Recognition memory is an im-portant
aspect of human declarative memory and is one of theroutine memory
abilities altered in patients with amnesticsyndrome and Alzheimers
disease (Hildebrandt et al. 2013;Peters et al. 2013; Squire et al.
2007). One of the mostcommon tasks for assessing recognition memory
in rodentsis the novel object preference (NOP) paradigm, which
resem-bles the visual paired comparison (VPC) task given to
humansubjects (Ennaceur 2010). Unlike other recognition
memorytasks, delayed matching to sample and delayed nonmatchingto
sample that involve an initial phase of rule learning, theNOP
paradigm capitalizes on the animals innate preference
Electronic supplementary material The online version of this
article(doi:10.1007/s00213-014-3577-3) contains supplementary
material,which is available to authorized users.
D. Reiss :O. Walter : L. Bourgoin :B. L. Kieffer :A.
-
for novelty. The standard procedure consists of prehabituationto
spatial context alone followed by an acquisition sessionduring
which rats or mice are familiarized with two identicalobjects. In
the testing trial, a novel object is presented togetherwith one of
the previously encountered sample objects andrecognitionmemory is
reflected by a greater exploration of thenovel object than the
familiar one. Variants of the procedurehave also been developed to
assess spatial-, temporal-, andepisodic-like memory (Balderas et
al. 2008; Barker andWarburton 2011; Dere et al. 2007; Dix and
Aggleton 1999;Eacott and Norman 2004; Wilson et al. 2013a). For
instance,the object-in-context procedure has been used to assess a
formof associative recognition memory that is considered as
ananalog of human episodic memory (Balderas et al. 2008;Langston
and Wood 2010; Wilson et al. 2013b). The proce-dure consists of two
successive acquisition trials in which theanimals are exposed to
two different pairs of identical objectslocated within two distinct
contexts. In the testing trial, bothtypes of objects are presented
in one of these familiar contexts.Normal rats or mice tend to
explore more the objects presentedin an incongruent familiar
context indicating that they haveremembered the previously
encountered object-context asso-ciation. Since its introduction,
the NOP task has rapidlygained popularity as a recognition memory
test for rodents.The relative simplicity of this paradigm has
allowed for wide-spread use across disciplines to evaluate the
cognitive alter-ations associated with aging, genetic
manipulations, and phar-macological interventions in rodents
(Aggleton et al. 2012;Antunes and Biala 2012; Bertaina-Anglade et
al. 2006; Dereet al. 2007; Ennaceur 2010; Lyon et al. 2012; Winters
et al.2010). However, the manual scoring of the test is both
timeand labor intensive, which limits its utilization for
high-throughput behavioral phenotyping and
pharmacologicalscreening. To overcome these limitations, automated
versionsof the task have been successfully developed by
severalgroups using video-tracking systems (Benice and Raber2008;
Chambon et al. 2011; Rutten et al. 2008).
In the present study, we introduce a new automated methodfor
assessing associative recognition memory that adopts thebasic
concept behind the NOP and VPC paradigms. Theprocedure is conducted
in an operant chamber and involvesdiscrimination of novel from
familiar nose-poke units (NPUs)that are distinguishable by their
visual features and spatiallocation. During the acquisition
session, mice are familiarizedwith the spatial context in the
presence of blinking NPU, andduring the choice session, a novel
nonblinking NPU isinserted into an empty spatial location.
Recognition memoryis assessed by comparing the amount of
exploration (numberof nose poking) dedicated to each set of NPU. A
series ofcontrol studies were conducted to establish that mice
reliablydiscriminate novel from familiar NPU. We first
examinedwhether discrimination between novel and familiar NPUvaries
as a function of the length of the acquisition period
and the retention delay. The effects of amnestic drugs
onrecognition memory were also assessed using systemic
ad-ministration of scopolamine, an antagonist of the
muscariniccholinergic receptors, and MK-801, an antagonist of the
glu-tamatergic NMDA receptors.
To demonstrate another important potential use of the nose-poke
recognition task, we studied the reconsolidation phe-nomenon.
Compelling evidence now indicates that well-established memories
can return to a labile state when re-trieved and again need to be
restabilized in order to persist(Finnie and Nader 2012; Sara 2000).
One hypothesized func-tion of the destabilization-restabilization
(or reconsolidation)process is to mediate the updating of a memory
to maintain itspredictive relevance (Finnie and Nader 2012; Kroes
andFernandez 2012; Lee 2009). The destabilization of neuraltrace is
thought to enable incorporation of new relevant infor-mation
present during retrieval into preexisting memory rep-resentation,
but this hypothesis is not unanimously accepted.While some studies
have demonstrated that memoryreconsolidation occurs only under
retrieval circumstances thatfavor novel information encoding (Jones
et al. 2012; Morriset al. 2006; Pedreira et al. 2004; Rossato et
al. 2007; Winterset al. 2009, 2011), others reported that the
association of newinformation to retrieved memory requires a
consolidation-likemechanism (Alberini 2011; Suarez et al. 2010;
Tronel et al.2005). More recently, new computational and
theoreticalmodels have been proposed to explain how in
hippocampal-dependent tasks the availability of novel information
duringrecall may trigger memory updating (reconsolidation
process)or new learning (consolidation process) as a function of
thedegree of similarity/dissimilarity that exists between the
eventpresent at memory recall and the previously memorized
expe-rience (Besnard et al. 2012; Osan et al. 2011). Here,
wemanipulated the components of the operant chamber duringa brief
reactivation trial interposed between the acquisitionand choice
sessions to explore whether the engagement ofmemory reconsolidation
depends on the magnitude and/or thetype of the transformation
introduced into the familiar spatialcontext.
Materials and methods
Subjects
Eight-week-old C57BL/6 N (BL6N) and C57/BL6J (BL6J)male were
purchased from the Charles River Laboratory(France). Mice were
housed four per cage and maintained ona 12:12 h light/dark cycle
with free access to food and waterand allowed to acclimatize to
housing conditions until testing,at the age of 10 to 13 weeks. All
experimental procedureswere conducted with the approval of the
local ethics commit-tee (CREMEAS) based on adherence to European
Union
4338 Psychopharmacology (2014) 231:43374347
-
guidelines (European Community Guidelines on the Care andUse of
Laboratory Animals 86/609/EEC).
Drugs
Scopolamine hydrobromide (Sigma, France) and MK-801(Sigma, St
Quentin Fallavier, France) were dissolved in phys-iological saline
(0.9%NaCl). Drugs were injected at a volumeof 10 ml/kg either
subcutaneously (scopolamine) or intraper-itoneally (MK-801). A
30-min pretreatment time was used inall experiments. The dose of
scopolamine and MK-801 wasselected based on our previous studies
(Goeldner et al. 2008,2009; Reiss et al. 2012).
Apparatus
Testing was carried out in four five-choice operant
chambers(Coulbourn Instruments, Allentown, USA) dimly lit with
apermanent house light. The front of the operant chamber wascurved
and composed of five bays filled with metal wallpanels
interchangeable with nose-poke modules (ModelH21-10 M). Each
nose-poke hole is equipped with a con-trolled yellow LED cue light
at the end and infrared photobeam across the opening that detects
the number of nosepokes. The back wall was composed of a single bay
fittedwith metal panels, and the plexiglass side walls
werecompletely covered by cardboard with distinguishable
geo-metrical motifs. The metal stainless-steel rod floor (the
gridshock floor provided by the manufacturer) was covered by agrey
vinyl-coated paper that was used as the standard flooringthroughout
the study. An infrared activity monitor (ModelH24-61MC) placed on
the ceiling was used for measuringthe animal locomotor
activity.
Experimental procedures
The standard nose-poke recognition protocol comprised
anacquisition session followed by a 10-min choice session.
Theacquisition session consisted of the familiarization with
thespatial context in the presence of a blinking nose-poke
unit(NPU: two adjacent nose-pokemodules spaced 4 cm apart andturned
on with a blinking cue light) presented either in theright or the
left corner of the front wall. The spatial location ofNPUwas
counterbalanced between mice for each condition orpharmacological
treatment. In the choice session, the familiarNPU was presented in
the same corner as in the acquisition,and a novel nonblinking NPU
(turned on with constant cuelight) was introduced in the opposite
corner (8 cm apart fromfamiliar NPU). The present experimental
design was adoptedbased on a series of preliminary experiments
showing that thevisual features of the familiar NPU do not impact
noveltydiscrimination (supplementary Fig. 1A). The number of
nosepokes made in each set of NPU was monitored during 10 min.
The recognition index (RI) was expressed by the ratio (100total
number of exploration of novel NPU) / (total number ofexploration
of all NPU). An RI of 50 % corresponds to achance level whereas a
higher RI reflects a good recognition.
The reactivation protocol comprised a trial of 3-min
durationinterposed between the acquisition and the choice sessions.
A1-day intertrial delay was used in all experiments.
Duringreactivation, familiar NPU and chamber floor were either
ma-nipulated separately or conjointly. The manipulation of
familiarNPU consists of removing the entire modules and replacing
itbymetal wall panels.Manipulation of chamber floor consists
ofremoving the grey vinyl-coated paper and keeping the
metalstainless-steel grids as new flooring. For all experiments,
priorto reactivation, mice were assigned into testing groups that
hadboth an equivalent number of nose pokes and levels of loco-motor
activity during acquisition session.
Statistical analysis
All data are expressed as mean group valuestandard error ofthe
mean (SEM) and analyzed using Students t test, one-way,or two-way
ANOVA as appropriate.When relevant, data weresubmitted to post hoc
Fishers protected least significant dif-ference (PLSD) test
analysis. One-sample Students t test wasused to compare recognition
index values to chance level(50 %). The criterion for statistical
significance was p0.05, Students ttest), demonstrating the lack of
unconditioned preference forone set of these cues. Alternately,
preference for the novelNPU (nonblinking one) increased as a
function of the acqui-sition session. Mice exposed for 5 min to the
context failed todistinguish the novel from the familiar NPU,
whereas thoseexposed for longer durations, 10 or 20 min, displayed
a clearpreference for the novel NPU (Table 1). One-way
ANOVAperformed on discrimination scores (Fig. 1a) revealed a
sig-nificant main effect of duration ((F3, 24)=3.12, p
- post hoc analysis confirmed that the 20-min group had a
betterrecognition performance compared with the control
group(p
- kg) or MK-801 (0.1 mg/kg) prior to the acquisition and
testedthe following day. Control groups received systemic
injectionsof the corresponding vehicles. As expected, scopolamine
pro-duced dose-dependent memory impairment (Fig. 3a). One-way ANOVA
revealed a significant effect of the treatment((F2, 21)=3.62,
p
-
4 and 5 show that novelty encoding during retrieval wasnecessary
for the engagement of memory reconsolidation.
Experiment 6 In subsequent studies, we examined
whethermanipulation of the chamber flooring could promote
thereconsolidation phenomenon. To this end, the smooth vinyl-coated
paper used as the standard flooring was replaced bystainless-steel
grid flooring (see Materials and methodssection). Mice were
submitted to 20-min familiarization inthe standard context and
treated the following day with sco-polamine (1 mg/kg) or MK-801
(0.1 mg/kg) prior to reactiva-tion with the new flooring. Memory
retention was assessed24 h later (48 h post-acquisition) in the
original learningcontext. Figure 5a shows that none of the
antagonists impaireddiscrimination performance compared with the
correspondingvehicle treatments (p>0.05, Students t test),
suggesting that
original memory trace remained intact upon retrieval. A seriesof
experiments were then conducted to investigate whetherencoding of
novel changes was mediated by a consolidation-like mechanism. We
first verified whether in the presence ofthe new flooring mice
still displayed preference for the novelNPU. To achieve this,
animals were familiarized during20 min with the standard context
and tested the followingday in the presence of the new flooring. As
observed, trainedmice behave like nave animals (p>0.05 vs chance
level, one-sample Students t test, Fig. 5b). This shows that in
thepresence of new flooring, trained mice treated the familiarNPU
as a novel cue. We then examined whether the briefreactivation with
the new chamber flooring was sufficient formice to acquire a
long-term recognition memory. Figure 5bshows that control mice
familiarized with the standard contextand tested 48 h later in the
presence of the new flooringperformed at chance level (p>0.05,
one-sample t test), repli-cating previous results. By contrast,
those submitted to thereactivation trial had a good recognition
performance com-pared with the control group (p
- the modified spatial context and tested the following day inthe
standard context. Nonreactivated mice tested directly inthe
original spatial context performed significantly abovechance
(p
-
associative recognition memory (the association of the
familiarNPU with the old chamber configuration). All together,
theseobservations suggest that the nose-poke recognition task
assessescontextual recognitionmemory and not only
recognitionmemoryfor individual item.
As mentioned earlier, a challenge to the
memory-updatinghypothesis of reconsolidation comes from a set of
studiesshowing that novel information encoding during retrieval
doesnot systematically engage destabilization of reactivated
mem-ory (Alberini 2011; Pedreira and Maldonado 2003; Suarez
24 h24 h20 min
a
Rec
ogni
tion
Inde
x (%
)
MK-801Scopolamine
20 min24 h24 h
24-48 h
Naive
24 h 48 h
b24 h24 h
c20 min
MK-801Scopolamine
Fig. 5 Manipulation of chamber flooring alone did not trigger
memoryreconsolidation. a Twenty-four hours after acquisition (20
min) in thestandard context, mice were treated with scopolamine (1
mg/kg, n=12,black bar), MK-801 (1 mg/kg, n=7, black bar), or
corresponding vehicle(white bars, n=11 and 7, respectively) prior
to reactivation with newflooring. Testing was carried the following
day (48 h post-acquisition) inthe standard context. b Reactivation
with new flooring promotes memorychanges. Dashed bar, nave mice
tested directly in the modified context.White bars, mice
familiarized with standard context and tested 24 (n=6) or48 h
(n=10) later in the modified context. Grey bar, mice reactivated
with
the new floor and tested the following day in the modified
context (n=6). cMice submitted to a 20-min learning session in the
standard context andtreated with scopolamine (1 mg/kg, black bar,
n=7), MK-801 (0.1 mg/kg,black bar, n=7), or corresponding vehicles
(white bars, n=8 and 6, respec-tively) prior to reactivation in
themodified context. Testingwas carried 24 hlater (48 h
post-acquisition) in the same modified context. Values are meanof
%RI SEM. The horizontal arrows denote the passage of time.
Thevertical arrows stand for drug injections. The dashed line shows
a chancelevel of 50 %. *p
-
et al. 2010). A number of explanations have been promulgatedover
the past years to reconcile the disparate evidence (Finnieand Nader
2012; Lee 2009; McKenzie and Eichenbaum 2011;Nadel et al. 2012;
Pedreira et al. 2004; Rodriguez-Ortiz andBermudez-Rattoni 2007).
More recently, Besnard et al. (2012)have proposed a theoretical
model that explains why inhippocampal-dependent tasks the
availability of novel infor-mation during recall may lead to memory
updating or newlearning (see also (Osan et al. 2011). They posit
that a highdegree of similarity will trigger the reconsolidation
processthat mediates the updating of old-memory
representation,while a low degree of similarity will engage the
consolidationprocess that supports formation of new-memory
representa-tion. The present study provides empirical evidence in
supportof this prediction by showing that the engagement
ofreconsolidation depends on the magnitude of context
changesintroduced during retrieval. Specifically, a substantial
trans-formation of the spatial context, such as removal of the
NPUand replacement of the chamber flooring, led to the formationof
a new competing memory (Fig. 6a), as indicated by theprotective
effect of scopolamine (Fig. 6b). By contrast, aminor context
transformation, the removal of the NPU, trig-gered memory
reconsolidation (Fig. 4a and supplementaryFig. 1B). Indeed, the
fact that reexposure to the standardcontext without the familiar
NPU rendered recognition mem-ory susceptible to the amnestic
treatments suggests that theoriginal memory trace underwent a
destabilization process. Asa consequence, the blockade of
muscarinic or NMDA recep-tors prior to the reactivation prevented
not only the encodingof the novel information but also the
restabilization of theoriginal memory trace, thereby resulting in
amnesia. It mightbe argued that these antagonists may have simply
speeded upmemory loss upon reactivation. However, the set of
studiesconducted with the manipulation of chamber floor either
alone(Fig. 5a) or conjointly with the NPU (Fig. 6b) argues
againstthis possibility. It should be also stressed that neither
scopol-amine nor MK-801 impaired recognition memory when
ad-ministered in the home cage (Fig. 4b) or prior to reactivationin
the presence of the familiar NPU (Fig. 4c and supplemen-tary Fig.
1C) suggesting that the engagement ofreconsolidation only occurs
when the retrieved memory needsto be updated with new relevant
information in the environ-ment. Overall, our findings corroborate
previous studiesshowing that a dual encoding retrieval state is
necessaryto trigger destabilization of the memory trace and
pro-vide new behavioral evidence supporting the memory-updating
hypothesis of reconsolidation.
An interesting finding was that the engagement of
memoryreconsolidation was also dependent on the type of
contextchanges introduced during retrieval. Unlike removal of
theNPU (Fig. 4a and supplementary Fig. 1B), replacement of
thechamber flooring did not trigger destabilization of the
originalmemory (Fig. 5a). These results may be explained by the
fact
that mice have a greater contact with the chamber floor andthat
the sensory experiences (e.g., visual, tactile, propriocep-tive,
etc.) elicited by the new (stainless-steel grids) and the
old(smooth vinyl-coated paper) floorings are radically distinct.As
such, upon reexposure to the chamber, the novel sensoryexperience
is encoded as a distinct episodic memory fromolder one. Consistent
with this idea, when familiarized micewere directly tested in the
presence of new flooring, theybehave like nave animals and engaged
in active sampling ofall sets of NPU (Fig. 5b), more likely to form
a new memoryrepresentation. This result extends those reported in
the fearconditioning paradigm showing that mice treated the
condi-tioning context as a novel environment when the floor
texturewas modified, a phenomenon illustrating a form of
behavioralpattern separation (McHugh et al. 2007). Further evidence
thatanimals use sensory information supplied by the floor
todiscriminate between similar environments comes from
elec-trophysiological studies in rats showing that modifying
thefloor color alone resulted in activation of completely
differentassemblies of hippocampal place cells (global remapping
orpattern separation process) like changing the entire
recordingchamber, thus reflecting the creation of a new
hippocampalrepresentation or spatial map for the modified
environment(Jeffery 2007; Jeffery and Anderson 2003).
Interestingly, thebrief re-reactivation episode with the new
flooring was suffi-cient for the familiarized mice to acquire a
long-term recog-nition memory (Fig. 5b and c), while a longer
duration(>5 min) was necessary for naive mice (Fig. 1a).
Furtherstudies are required to clarify whether the learning
improve-ment displayed by reactivated mice reflects formation of
newindependent memory or a form of memory updating (orintegrative
encoding), which consists of linking together noveland retrieved
context information by a consolidation-likemechanism (Alberini
2011).
In conclusion, the above findings demonstrate that our
newautomated method using the NPU permits a rapid and reliableway
for assessing recognition memory in rodents. Eventhough the
procedure described here can be used in its currentversion for
characterizing the effects of various pharmacolog-ical and genetic
manipulations on recognition memory, furtheroptimization of the
procedure might be necessary dependingupon the experimental
conditions (e.g., mouse strains, types ofoperant chambers, etc) and
the questions addressed. Oneshortcoming of the current experimental
design lies in the factthat animals can only be tested once, but
this may be over-come by implementing few modifications to make it
suitablefor repeated testing, for instance, by shortening the
initialacquisition session (e.g., 10 min) to prevent an
over-habituation of the animals to the chamber and by performingthe
testing in the presence of a novel NPU configuration (e.g.,blinking
or nonblinking NPU displaced to a novel spatiallocation or a third
NPU unit introduced in an empty location).For routine screening of
new drugs and behavioral
Psychopharmacology (2014) 231:43374347 4345
-
phenotyping of new mouse lines, counterbalancing for theidentity
of the NPU as well the spatial location is also recom-mended to
control for a potential nonspecific changes innovelty
discrimination. Overall, the development of thenose-poke
recognition task should provide a valuable com-plement to existing
rodent learning paradigms by offering newpossibilities for
assessing contextual memory and decipheringthe neural and genetic
mechanisms underpinning thereconsolidation process.
Acknowledgments This work was supported by grants from the
CentreNational de la Recherche Scientifique (CNRS), the Institut
National de laSant et de la Recherche Mdicale (INSERM), the
Universit de Stras-bourg (UDS). The authors thank Dr. Steve Brooks
for the Englishcorrections.
References
Aggleton JP, BrownMW, Albasser MM (2012) Contrasting brain
activitypatterns for item recognition memory and associative
recognitionmemory: insights from immediate-early gene functional
imaging.Neuropsychologia 50:31413155
Alberini CM (2011) The role of reconsolidation and the dynamic
process oflong-termmemory formation and storage. Front Behav
Neurosci 5:12
Antunes M, Biala G (2012) The novel object recognition
memory:neurobiology, test procedure, and its modifications. Cogn
Process13:93110
Balderas I, Rodriguez-Ortiz CJ, Salgado-Tonda P, Chavez-Hurtado
J,McGaugh JL, Bermudez-Rattoni F (2008) The consolidation ofobject
and context recognition memory involve different regionsof the
temporal lobe. Learn Mem 15:618624
Barker GR, Warburton EC (2011) When is the hippocampus involved
inrecognition memory? J Neurosci 31:1072110731
Benice TS, Raber J (2008) Object recognition analysis in mice
usingnose-point digital video tracking. J Neurosci Methods
168:422430
Bertaina-Anglade V, Enjuanes E, Morillon D, Drieu la Rochelle C
(2006)The object recognition task in rats and mice: a simple and
rapidmodel in safety pharmacology to detect amnesic properties of a
newchemical entity. J Pharmacol Toxicol Methods 54:99105
Besnard A, Caboche J, Laroche S (2012) Reconsolidation of
memory: adecade of debate. Prog Neurobiol 99:6180
Boccia MM, Baratti CM (1999) Effects of oxytocin and an
oxytocinreceptor antagonist on retention of a nose-poke habituation
responsein mice. Acta Physiol Pharmacol Ther Latinoam 49:155160
Bozon B, Davis S, Laroche S (2003) A requirement for the
immediateearly gene zif268 in reconsolidation of recognition memory
afterretrieval. Neuron 40:695701
Brodkin J (1999) Assessing memory in mice using habituation of
nose-poke responding. Behav Pharmacol 10:445451
Chambon C,Wegener N, Gravius A, DanyszW (2011) A new
automatedmethod to assess the rat recognition memory: validation of
themethod. Behav Brain Res 222:151157
Dere E, Huston JP, De Souza Silva MA (2007) The
pharmacology,neuroanatomy and neurogenetics of one-trial object
recognition inrodents. Neurosci Biobehav Rev 31:673704
Dix SL, Aggleton JP (1999) Extending the spontaneous preference
test ofrecognition: evidence of object-location and object-context
recogni-tion. Behav Brain Res 99:191200
Dodart JC, Mathis C, Ungerer A (1997)
Scopolamine-induceddeficits in a two-trial object recognition task
in mice.Neuroreport 8:11731178
Eacott MJ, Norman G (2004) Integrated memory for object, place,
andcontext in rats: a possible model of episodic-like memory?
JNeurosci 24:19481953
Ennaceur A (2010) One-trial object recognition in rats and mice:
meth-odological and theoretical issues. Behav Brain Res
215:244254
Finnie PS, Nader K (2012) The role of metaplasticity mechanisms
inregulating memory destabilization and reconsolidation.
NeurosciBiobehav Rev 36:16671707
Goeldner C, Reiss D, Wichmann J, Meziane H, Kieffer BL,
OuagazzalAM (2008) Nociceptin receptor impairs recognition memory
viainteraction with NMDA receptor-dependent mitogen-activated
pro-tein kinase/extracellular signal-regulated kinase signaling in
thehippocampus. J Neurosci 28:21902198
Goeldner C, Reiss D, Wichmann J, Kieffer BL, Ouagazzal AM
(2009)Activation of nociceptin opioid peptide (NOP) receptor
impairscontextual fear learning in mice through glutamatergic
mechanisms.Neurobiol Learn Mem 91:393401
Hildebrandt H, Fink F, Kastrup A, Haupts M, Eling P (2013)
Cognitiveprofiles of patients with mild cognitive impairment or
dementia inAlzheimers or Parkinsons disease. Dement Geriatr Cogn
Dis Extra3:102112
Jeffery KJ (2007) Integration of the sensory inputs to place
cells: What,where, why, and how? Hippocampus 17:775785
Jeffery KJ, Anderson MI (2003) Dissociation of the geometric
andcontextual influences on place cells. Hippocampus 13:868872
Jones B, Bukoski E, Nadel L, Fellous JM (2012) Remaking
memories:reconsolidation updates positively motivated spatial
memory in rats.Learn Mem 19:9198
KroesMC, Fernandez G (2012)Dynamic neural systems enable
adaptive,flexible memories. Neurosci Biobehav Rev 36:16461666
Langston RF, Wood ER (2010) Associative recognition and the
hippocam-pus: differential effects of hippocampal lesions on
object-place, object-context and object-place-context memory.
Hippocampus 20:11391153
Lee JLC (2009) Reconsolidation: maintaining memory relevance.
TrendsNeurosci 32:413420
Lyon L, Saksida LM, Bussey TJ (2012) Spontaneous object
recognitionand its relevance to schizophrenia: a review of findings
from phar-macological, genetic, lesion and developmental rodent
models.Psychopharmacology (Berl) 220:647672
McHugh TJ, Jones MW, Quinn JJ, Balthasar N, Coppari R, Elmquist
JKet al (2007) Dentate gyrus NMDA receptors mediate rapid
patternseparation in the hippocampal network. Science 317:9499
McKenzie S, Eichenbaum H (2011) Consolidation and
reconsolidation:two lives of memories? Neuron 71:224233
Morris RG, Inglis J, Ainge JA, Olverman HJ, Tulloch J, Dudai Y
et al(2006) Memory reconsolidation: sensitivity of spatial memory
toinhibition of protein synthesis in dorsal hippocampus
duringencoding and retrieval. Neuron 50:479489
Nadel L, Hupbach A, Gomez R, Newman-Smith K (2012)
Memoryformation, consolidation and transformation. Neurosci
BiobehavRev 36:16401645
Osan R, Tort AB, Amaral OB (2011) A mismatch-based model
formemory reconsolidation and extinction in attractor networks.
PlosOne 6:e23113
Pedreira ME, Maldonado H (2003) Protein synthesis
subservesreconsolidation or extinction depending on reminder
duration.Neuron 38:863869
Pedreira ME, Perez-Cuesta LM,MaldonadoH (2004)Mismatch
betweenwhat is expected and what actually occurs triggers
memoryreconsolidation or extinction. Learn Mem 11:579585
Peters F, Villeneuve S, Belleville S (2013) Predicting
progression todementia in elderly subjects with mild cognitive
impairment usingboth cognitive and neuroimaging predictors. J
Alzheimers Dis 38:307318
Reiss D, Prinssen EP, Wichmann J, Kieffer BL, Ouagazzal AM
(2012)The nociceptin orphanin FQ peptide receptor agonist,
Ro64-6198,
4346 Psychopharmacology (2014) 231:43374347
-
impairs recognition memory formation through interaction
withglutamatergic but not cholinergic receptor antagonists.
NeurobiolLearn Mem 98:254260
Rodriguez-Ortiz CJ, Bermudez-Rattoni F (2007)
Memoryreconsolidation or updating consolidation?
Rossato JI, Bevilaqua LR, Myskiw JC, Medina JH, Izquierdo
I,Cammarota M (2007) On the role of hippocampal protein synthesisin
the consolidation and reconsolidation of object recognition
mem-ory. Learn Mem 14:3646
Rutten K, Reneerkens OA, Hamers H, Sik A, McGregor IS,
Prickaerts Jet al (2008) Automated scoring of novel object
recognition in rats. JNeurosci Methods 171:7277
Sara SJ (2000) Retrieval and reconsolidation: toward a
neurobiology ofremembering. Learn Mem 7:7384
Squire LR,Wixted JT, ClarkRE (2007)Recognitionmemory and
themedialtemporal lobe: a new perspective. Nat Rev Neurosci
8:872883
Suarez LD, Smal L, Delorenzi A (2010) Updating contextual
informationduring consolidation as result of a new memory trace.
NeurobiolLearn Mem 93:561571
Tronel S, Milekic MH, Alberini CM (2005) Linking new information
to areactivated memory requires consolidation and not
reconsolidationmechanisms. PLoS Biol 3:e293
Wilson DI, Langston RF, Schlesiger MI, Wagner M, Watanabe S,
AingeJA (2013a) Lateral entorhinal cortex is critical for novel
object-context recognition. Hippocampus 23:352366
Wilson DI, Watanabe S, Milner H, Ainge JA (2013b) Lateral
entorhinalcortex is necessary for associative but not
nonassociative recogni-tion memory. Hippocampus
Winters BD, Tucci MC, DaCosta-Furtado M (2009) Older and
strongerobject memories are selectively destabilized by
reactivation in thepresence of new information. Learn Mem
16:545553
Winters BD, Saksida LM, Bussey TJ (2010) Implications of
animalobject memory research for human amnesia.
Neuropsychologia48:22512261
Winters BD, Tucci MC, Jacklin DL, Reid JM, Newsome J (2011) On
thedynamic nature of the engram: evidence for circuit-level
reorgani-zation of object memory traces following reactivation. J
Neurosci31:1771917728
Psychopharmacology (2014) 231:43374347 4347
New automated procedure to assess context recognition memory in
miceAbstractAbstractAbstractAbstractAbstractIntroductionMaterials
and methodsSubjectsDrugsApparatusExperimental proceduresStatistical
analysis
ResultsNose-poke recognition memory as a function of the
acquisition length and the retention delayRelationship between
nose-poke recognition performance and exploratory behaviorEffect of
amnestic treatments on nose-poke recognition memory formationEffect
of spatial context transformations on recognition memory stability
upon retrieval
DiscussionReferences