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Neurobiology of Learning and Memory 89 (2008) 352–359

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Intrahippocampal anisomycin infusions disrupt previously

consolidated spatial memory only when memory is updated
Carlos J. Rodriguez-Ortiz a, Paola Garcia-DeLaTorre a, Eduardo Benavidez a,
Maria Angeles Ballesteros b, Federico Bermudez-Rattoni a,*
a
Departamento de Neurociencias, Instituto de Fisiologı́a Celular, Universidad Nacional Autónoma de México, México D.F. 04510, Mexico
b
Departamento de Psicologı́a Experimental y Conducta, Universidad de Granada, 18071 España, Spain

Received 14 July 2007; revised 8 October 2007; accepted 11 October 2007

Abstract

Reconsolidation has proven to be a common phenomenon relevant to memory processing. However, the functional significance of
this process is still a matter of debate. Previous work has shown that reconsolidation is indeed a process by which updated information
is integrated, through the synthesis of proteins, to a memory trace. To further analyze the role that updated information plays in
retrieved spatial memory susceptibility to disruption, we injected anisomycin bilaterally in the dorsal hippocampus of Wistar rats.
Implanted animals were trained for 5 days on the Morris water maze (MWM) task and injected with anisomycin before the third or fifth
training session. When memory was assessed a week later, only animals injected on the third training session showed disruption of long-
term memory. Furthermore, when animals were trained for either 3 (middle-trained) or 5 (well-trained) days and a week later anisomycin
was infused before a reminder session, only middle-trained rats infused with anisomycin showed reduced performance when tested for
long-term memory. Finally, animals trained for 5 days and injected with anisomycin 7 days later on an extinction session showed
impaired long-term extinction when tested. These results suggest that for spatial memory tasks acquisition of updated information is
a necessary feature to undergo this process. We propose that reconsolidation is not an accurate term because it implies that consolidation
happens again. This conception does not fit with the evidence; hence, we suggest that updating consolidation is a more descriptive term to
refer to this process.
 2007 Elsevier Inc. All rights reserved.

Keywords: Memory update; Reconsolidation; Spatial memory; Morris water maze; Anisomycin; Hippocampus

1. Introduction However, Nader, Schafe, and LeDoux (2000) demon-

Protein synthesis is a key step in the formation of long-
term memories. A number of experimental studies have
shown that inhibition of protein synthesis around the time
of training causes long-term memory impairment in a large
number of species and in different memory tasks (Davis &
Squire, 1984; McGaugh, 1966; McGaugh, 2000). Until
recently, it was widely accepted that long-term memories
require of protein synthesis exclusively during a time win-
dow after acquisition (Kandel, 2001; McGaugh, 2000).
*
Corresponding author. Fax: +52 55 56 22 56 07.
E-mail address: fbermude@ifc.unam.mx (F. Bermudez-Rattoni).
strated that after retrieval, long-term memories need pro-
tein synthesis again to be retained in long-term storage.
This finding has been replicated by many others (Dudai,
2004). Consequently, memory retrieval has grasped more
attention and is currently seen as a dynamic phase in mem-
ory processing (Dudai, 2004; Sara, 2000; Suzuki et al.,
2004). Therefore, to describe the relevant features that
account for long-term memory dependence on protein syn-
thesis after retrieval is now of general interest in the field.
Most of the reports that have dealt with retrieved mem-
ory dependence on protein synthesis have used tasks in
which a conditioned stimulus (CS) is paired with an uncon-
ditioned stimulus (US). A conditioned response is obtained
and used as a measure of memory. Commonly, on the

1074-7427/$ - see front matter  2007 Elsevier Inc. All rights reserved.
doi:10.1016/j.nlm.2007.10.004
 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359
retrieval trial, the CS is presented without the US and
extinction may be initiated. On extinction, the CS is associ-
ated to the absence of the US. The CS–noUS association
requires protein synthesis if it is to remain long-lasting.
Therefore, a competition between the CS–US and the
CS–noUS memories takes place during memory retrieval.
In this regard, it has been observed that if the retrieval trial
induces extinction, then protein synthesis inhibition dis-
rupts the long-term extinction memory. Conversely, if the
retrieval trial does not initiate extinction, then protein syn-
thesis inhibition impairs the long-term CS–US memory
(Eisenberg, Kobilo, Berman, & Dudai, 2003; Pedreira &
Maldonado, 2003). In addition, it has been reported that
stronger and older memories need longer retrieval trials
to be disrupted by the blockade of protein synthesis com-
pared to weaker and younger memories as long as the
retrieval trial does not lead to extinction (Suzuki et al.,
2004). Hence, it seems that the strength and duration of
the reminder are pivotal traits directly related to memory
susceptibility to disruption after retrieval.
Recently, we have found that in a taste-recognition
memory task, retrieved long-term memory is dependent
on protein synthesis only when updated information is
acquired. So as long as task performance can be improved,
protein synthesis inhibition disrupts retrieved memory.
Consistently, when task performance has reached an
asymptotic level, protein synthesis inhibition does not
impair memory after retrieval. These results suggest that
retrieved memory can be modified as part of a protein syn-
thesis-dependent process aimed at the integration of
updated experience to long-term memory (Rodriguez-
Ortiz, De la Cruz, Gutierrez, & Bermudez-Rattoni, 2005).
To support the above, it is important to test whether
integration of updated information is an indispensable fea-
ture to observe disruption of retrieved memory by protein
synthesis inhibition in any given task. Despite recent evi-
dence that points to this direction (Lukowiak, Fras, Smyth,
Wong, & Hittel, 2007; Morris et al., 2006; Rossato et al.,
2007), acquisition of updated information is not currently
seen as a necessary trait for the reconsolidation process.
Therefore, we addressed this issue on the Morris water
Fig. 1. Photomicrography of a coronal section of an anisomycin-injected rat showing cannula track (CT) location in the dorsal hippocampus. Similar
results were observed for the rest of the implanted animals. On the left is a coronal diagram of the dorsal hippocampus (Reprinted with permission from
Paxinos & Watson, 1998).
353
maze (MWM) task, which is an extensively studied spatial
memory paradigm. In this task, animals learn to escape
from cool water by finding a hidden platform fixed into a
swimming pool. Animals guide by extra-maze spatial cues
located around the room to learn the platform position
(Morris, Garrud, Rawlins, & O’Keefe, 1982). Evidence
indicates that the hippocampus is an essential region for
spatial memory processing (Eichenbaum, 2000; Squire,
Stark, & Clark, 2004). Furthermore, protein synthesis in
the hippocampus is required for long-term spatial memory
(Guzowski & McGaugh, 1997; Naghdi, Majlessi, & Bozorg-
mehr, 2003; Rossato, Bevilaqua, Medina, Izquierdo, &
Cammarota, 2006). Moreover, it has been reported that
after retrieval, MWM memory requires protein synthesis
in this region to remain in long-term storage (Rossato
et al., 2006). Therefore, in the present study we assessed
the role that incorporation of updated information to mem-
ory plays in retrieved long-term spatial memory dependence
on protein synthesis, by infusing bilaterally anisomycin in
the dorsal hippocampus of rats. Parts of the results
described herein were previously presented in abstract form
(Rodriguez-Ortiz, Benavidez, Ballesteros, Garcia, & Ber-
mudez-Rattoni, 2005).
2. Materials and methods
2.1. Subjects
Male Wistar rats from Instituto de Fisiologı́a Celular breeding colony
weighing between 280 and 320 g at the beginning of the experiment were
housed individually in plastic cages and kept on a 12/12 light/dark cycle.
All manipulations were performed during the dark cycle. Food and water
were freely available throughout experiments.
2.2. Surgery and microinjection
Animals under ketamine–xylazine (76–8 mg/kg) anesthesia were bilat-
erally implanted with stainless-steel guide cannulae in the dorsal hippo-
campus. Coordinates from bregma were: posterior 3.6 mm, lateral +/
3.0 mm and ventral 2.3 mm. These coordinates were selected to inhibit
protein synthesis in the CA3–CA1 region (Fig. 1). The behavioral proce-
dures were performed after at least 5 days post-surgery. For bilateral micr-
oinjections, an injector (30 ga) was inserted into each guide cannula
354 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359
extending 1 mm below the cannula tip. Drugs (1 lL per hemisphere) were
infused over a period of 1 min and the injector was left in place for an
additional minute. Anisomycin (Sigma) was dissolved in equimolar HCl
and adjusted to 100 mg/mL, pH 7.5 in vehicle solution (ACSF, mM: NaCl
125, KCl 5, NaH2PO4ÆH2O 1.25, MgSO4Æ7H2O 1.5, NaHCO3 26, glucose
10, CaCl2 2.5). The anisomycin dose was chosen based on previous reports
showing that doses between 80 and 125 mg/mL produce protein synthesis
inhibition in the hippocampus and impairment on hippocampus-depen-
dent tasks (Debiec, LeDoux, & Nader, 2002; Vianna, Szapiro, McGaugh,
Medina, & Izquierdo, 2001).
2.3. Behavioral procedures
2.3.1. Morris water maze (MWM) training
The task was performed in a black circular swimming pool with a
diameter of 1.5 m and a height of 1.0 m. The pool was located in a dim-
light illuminated room containing several spatial cues. A 12 · 12 cm plat-
form was hidden 1 cm under the water in a constant location. Water tem-
perature was 21 ± 2 C during all training and probe sessions. A training
session consisted of 10 trials. On each trial, rats were placed in the pool in
one of the 10 different outset points in pseudorandom order. Animals were
allowed to swim for 60 s or until they reached the platform, allowing them
to remain on the platform for 30 s. Afterwards, they were placed in a wait-
ing cage for another 30 s until the following trial. Any rat that failed to
find the platform within 60 s was gently guided to it by hand.
2.3.2. Anisomycin injections on training
For these experiments, rats were trained in the MWM task for five con-
secutive sessions (10 trials per session) and were injected in the hippocampi
20 min before the training session either on session 3 or 5. A long-term test
session was performed 7 days after training (on day 12). On the test ses-
sion, rats swam without platform for 60 s.
2.3.3. Anisomycin injections on memory retrieval
For these experiments, rats were trained for either three or five consec-
utive sessions (10 trials per session) in the MWM task. Seven days after
training, rats were injected bilaterally in the dorsal hippocampus 20 min
before a reminder session (day 12). On the reminder session, animals swam
without the platform for 60 s. After that time period, the platform was
raised to its training location. Rats were allowed to swim for another
60 s or until they reached the platform. Rats sat on the platform for
30 s to avoid extinction. Any rat that did not find the platform within
the 60 s-period was guided to it by hand. Two additional groups were
trained for three consecutive sessions and a week later they were injected
in a different room without a reminder session. All groups were tested a
week after injection (day 19). On the test session, rats swam without the
platform for 60 s.
2.3.4. Anisomycin injections on memory extinction
For these experiments, rats were trained for five sessions in the MWM
task as described above. Seven days after training, rats were bilaterally
injected in the dorsal hippocampus 20 min before they were submitted to
three extinction trials. On each extinction trial, animals were placed in the
pool without the platform for 60 s. Rats were then placed in a waiting cage
for 30 s. A long-term memory test was performed 14 days after training (day
19). On the test session, animals swam without the platform for 60 s.
2.4. Histology
At the end of the experiments, rats were perfused and their brains
removed. 40 lm-thick brain sections were stained with cresyl violet and
examined by light microscopy for injector tip placement.
2.5. Data analysis
Experiments were recorded using a video tracking system chromotrack
(San Diego Instruments). The latencies to reach the platform were used as
a measure of acquisition. On retrieval and test sessions, the number of
crossings over a virtual 35 cm diameter around the platform was used as
a measure of memory. Mean velocity was evaluated to discount unspecific
effects of drugs on motor activity.
2.6. Statistical analysis
Repeated measures analysis of variance (ANOVA) was used to com-
pare mean ± SEM latencies to platform among groups across trials on a
particular day. The Fisher pair wise test was used for post hoc analysis
with p < .05 considered significant. Unpaired t-test was used to compare
task performance between anisomycin-infused and corresponding vehicle
groups on a particular trial.
3. Results
3.1. Intrahippocampal anisomycin infusions disrupt long-
term memory when applied earlier during acquisition
Under our working hypothesis, as long as information is
acquired, protein synthesis entails retrieved memory and
allows integration of updated information to long-term
memory. During MWM training, acquisition of informa-
tion is observed in search behavior along the training ses-
sions until performance plateau is reached. Hence,
impairment of retrieved memory should be detected by
protein synthesis inhibition during training. Therefore, ani-
mals were trained for 5 days and anisomycin injections in
the hippocampus were applied 20 min before the third or
the fifth training session. Fig. 1 shows a representative site
of injection into the dorsal hippocampus. Impairment of
performance was observed for the group injected with
anisomycin on day 3 during that training session. An
ANOVA for day 3 revealed significant effects of group
(F(3,28) = 4.95, p < .01) and trials (F(9,252) = 9.24, p < .01).
Fisher’s post hoc test revealed that the anisomycin group
was different from the vehicle group (p < .01) (Fig. 2A,
day 3). For the group injected on day 5 this effect was less
noticeable. An ANOVA with repeated measures for day 5
showed only an effect on trials (F(9,270) = 4.16, p < .01) and
a borderline effect of group (F(3,30) = 2.39, p = .087)
(Fig. 2A, day 5). The swimming speed was measured in
the third and fifth days to discount motility effects by
anisomycin administration. There were no significant dif-
ferences between groups on injections days as shown in
Fig. 2A (insets).
During the long-term test performed 7 days after the
last training session (day 12), memory disruption was
observed in the animals injected with anisomycin on
the third training day but not in those infused on the
fifth day (Fig. 2B). An unpaired t-test revealed that
the group injected with anisomycin on day 3 was differ-
ent from its respective vehicle group (t(15) = 3.19,
p < .05). Thus long-term memory is susceptible to dis-
ruption by anisomycin infusions applied on the third
day but not on the fifth day, supporting our hypothesis
that the crucial issue is whether or not updated material
is acquired.
 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359 355

Fig. 2. Hippocampal infusions of anisomycin disrupt long-term memory when applied earlier (on day 3) on acquisition. (A). Mean ± SEM latencies to
platform for each trial on training. Arrows indicate drug infusions. (solid circles, n = 8) vehicle on day 5; (open triangles, n = 9) anisomycin on day 5;
(crosses, n = 9) vehicle on day 3; (open squares, n = 8) anisomycin on day 3. Insets. Mean + SEM velocity on injection days. (B) Mean + SEM number of
crossings over platform on test session (day 12). *p < .05 between anisomycin-infused and corresponding vehicle groups.

3.2. Intrahippocampal anisomycin infusions disrupt retrieved 3.3. Intrahippocampal anisomycin infusions disrupt memory
memory only in middle-trained animals extinction

Animals were trained for 3 (middle-trained) or 5 (well-
trained) days and a week later anisomycin injections were
applied 20 min before a reminder session (day 12). Two
weeks after training rats were tested (day 19). As can be
seen on Fig. 3A, animals achieved asymptotic performance
after three training days. However, on retrieval, well-
trained animals displayed a better performance than those
who were trained only for 3 days (Fig. 3B, compare vehicle
groups). This result points out that long-term performance
can be significantly improved after the third training ses-
sion because of the further updated information that is
integrated to memory. Consistent with the results pre-
sented above, impairment on retrieval was observed for
the anisomycin-injected groups (Fig. 3B). In spite of this
effect, the only group that showed memory disruption
when tested was the one trained for 3 days and infused with
anisomycin on the reminder session (Fig. 3C). Unpaired
t-test revealed that the middle-trained group injected with
anisomycin before the reminder was different from the mid-
dle-trained group injected with vehicle solution (t(22) =
2.64, p < .05). These results support the idea that protein
synthesis is needed for retrieved memory to remain in
long-term storage only when updated information is
acquired. Accordingly, for well-trained animals, protein
synthesis inhibition did not interfere with retrieved memory
because updating did not take place. Importantly, memory
impairment caused by anisomycin infusions is dependent
on retrieval. Middle-trained animals infused with anisomy-
cin a week after training without retrieval session per-
formed the task as well as control animals when tested
(Fig. 3D).
To evaluate the effects on extinction, an experiment was
conducted where three extinction trials were performed for
some of the animals trained for 5 days. Seven days after
training anisomycin was administrated 20 min before the
first extinction trial and a test trial was carried out a week
later (day 19). Long-term extinction impairment was
observed on the test day (Fig. 4C). An unpaired t-test
revealed that the group injected with anisomycin before
the extinction session was different from its respective vehi-
cle group on test (t(16) = 2.70, p < .05). Extinction was
impaired by drug infusions presumably because updating
of the memory trace was required and so was protein syn-
thesis in the hippocampus. Together with the previous
experiments, the results in extinction suggest that when
information is relevant to a memory trace that was previ-
ously consolidated, protein synthesis occurs for this infor-
mation to be incorporated to the trace. Updating
information can either cause reconsolidation or extinction,
but they both require protein synthesis.
4. Discussion
Anisomycin is an abundantly used protein synthesis
inhibitor and its effects on memory consolidation have
been widely reported. Previous work has shown that aniso-
mycin infusions into the hippocampi disrupt memory con-
solidation; presumably, by means of protein synthesis
inhibition, leaving performance on the injection session
unimpaired (Quevedo et al., 1999; Vianna et al., 2001).
Hence, performance disruption was anticipated on the
day following injection, while performance on the injection
356 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359

Fig. 3. Anisomycin injections on the reminder session disrupt long-term memory for middle-trained animals in the MWM task. (A) Mean ± SEM
latencies for each trial of groups trained for 3 (solid circles, middle-trained) or 5 (open triangles, well-trained) days. (B) Anisomycin infusions affected
MWM performance on the injection day. Mean + SEM number of crossings over platform on reminder session (day 12). Injections were given 20 min
before this retrieval session. Well-trained anisomycin-treated rats showed impaired performance compared to their corresponding vehicles. (C) Only
middle-trained rats infused with anisomycin on retrieval showed significant reduced performance when tested for long-term memory. Mean + SEM
number of crossings over platform on test for groups with hippocampal injections and one trial on retrieval. Well-trained vehicle, n = 8; well-trained
anisomycin, n = 14; middle-trained vehicle, n = 11; middle-trained anisomycin n = 13. (D) Reminder session is necessary for memory disruption by
anisomycin injections. Mean + SEM number of crossings over platform on test for groups with hippocampal injections and no retrieval session. middle-
trained vehicle n = 8; middle-trained anisomycin, n = 8. *p < .05, **p < .01 between anisomycin-infused and corresponding vehicle groups.

session was expected to be the same as for control groups.
However, there are differences in the injection sites and the
task protocols used in the different studies. Therefore, sev-
eral explanations could account for the unexpected impair-
ment we observed on task performance on injection
sessions. Our results point to side effects of anisomycin
on task performance. In other research fields, anisomycin
is used as a kinases agonist. Anisomycin, in lower doses
than the ones used here, acts as a signaling activator for
the JNK and p38 kinases pathways, resulting in rapid
induction of immediate-early gene expression (Hazzalin,
Le Panse, Cano, & Mahadevan, 1998). Therefore, aniso-
mycin’s effect on performance may be due to an intracellu-
lar signaling activation that leads to a transient disruption
of performance on the injection session. Motor effects were
discarded because the swimming speed during the trials
was similar in spite of anisomycin infusions (Fig. 2A,
insets). Similarly, it can be claimed that the observed effects
on the long-term may be explained by state-dependency.
However, there was four other training days in the absence
of drug administration, this would decrease possible state-
dependency effects.
On Fig. 2A, the lack of improvement in performance on
the third training day points to anisomycin effects on short-
term memory. However, impairment was also observed
when anisomycin was applied on the retrieval session
where a single trial was carried out (Fig. 3B). Therefore,
it seems that anisomycin affected memory retrieval. Hence,
as noted above, the retrieval deficit may be due to a mis-
placed activation of some signaling pathways that leads
to disturbance of the intracellular mechanisms needed for
memory retrieval. To avoid effects on retrieval, injections
could have been applied on another time window. How-
ever, it has been previously shown that anisomycin injec-
tions do not cause consolidation disruption of the MWM
task neither if applied immediately after the session, nor
if applied an hour before session onset (Meiri & Rosenb-
lum, 1998). Consistently, we were unable to observe con-
solidation disruption with anisomycin injections after a
training session (not shown). Nevertheless, three recent
studies reported an effect on reconsolidation when injecting
anisomycin in the hippocampus after a retrieval session
(Morris et al., 2006; Rossato et al., 2006, 2007). Even so,
altogether the results reported herein suggest that the pro-
 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359 357

Fig. 4. Anisomycin infusions disrupt long-term extinction. (A) Mean ± SEM latencies for each trial of rats trained for 5 days. (B) Mean + SEM number
of crossings over platform for each extinction trial. Injections were given 20 min before the first trial. (C) Mean + SEM number of crossings on test for
groups with hippocampal injections and three trials on retrieval. (open bars, n = 9) vehicle; (gray bars, n = 9) anisomycin. *p < .05, **p < .01 between
anisomycin-infused and corresponding vehicle groups or between two trials for a particular group.

cess uncovered by anisomycin infusions is related to the
integration of updated information to a previously consol-
idated memory trace.
Przybyslawski and Sara (1997) reported that, like it
occurs in consolidation, an NMDA-dependent process is
required to retain consolidated memory in long-term stor-
age if it is reactivated by retrieval. This and similar obser-
vations, achieved with inhibitors or antagonists of different
molecules, led to the proposal that stable consolidated
memory becomes labile after retrieval; and that a protein
synthesis-dependent process similar to the one that
accounts for consolidation is required if retrieved memory
is to remain for the long term. This process is referred to as
reconsolidation (Nader, 2003; Sara, 2000). However, the
term reconsolidation implies that consolidation undergoes
once again, a notion that seems not to be supported by evi-
dence. For example, differences between the cellular events
that underlie these processes indicate that the post-retrieval
process is not a replica of consolidation (Hall, Thomas, &
Everitt, 2001; Kelly, Laroche, & Davis, 2003; Tronel &
Sara, 2002).
The idea that reconsolidation is a process related to
memory updates has previously been suggested (Gold,
2006; Lewis, 1979; Sara, 2000). Furthermore, Dudai
(2004) considers that upon retrieval the activated trace is
susceptible to modifications and that the observed disrup-
tion by consolidation blockers may be the price paid for
modifiability. However, experimental support was lacking
until very recently. In this regard, we have suggested, on
the basis of experimental evidence, that part of a previously
consolidated memory is susceptible to disruption only
when updated experience capable of modifying behavior
is acquired (Rodriguez-Ortiz et al., 2005). Transient sus-
ceptibility to disruption of a previously consolidated mem-
ory trace may be the physiological substrate that allows
incoming material to integrate to memory. Thus, it seems
that when updated material is capable of strengthening
or changing a previously consolidated memory trace, a
protein synthesis-dependent process is initiated to integrate
updated information to the memory trace. During this pro-
cess, previously consolidated memory is transiently desta-
bilized and by the infusion of protein synthesis blockers
it appears that the process is intended to consolidate mem-
ory again.
Further recent research suggest that reconsolidation is
aimed to update memory (Eschenko, Molle, Born, & Sara,
2006; Hupbach, Gomez, Hardt, & Nadel, 2007; Lukowiak
et al., 2007; Morris et al., 2006; Rossato et al., 2006; Ros-
sato et al., 2007; reviewed in: Rodriguez-Ortiz & Bermu-
dez-Rattoni, 2007; Tronson & Taylor, 2007). For
example, Rossato et al. (2007) trained rats on a recognition
memory task, where two different objects were presented in
a training session. On a second day, rats were exposed to
one of the objects presented the day before together with
a novel object and anisomycin was infused into the dorsal
hippocampus. When tested on the next day, memory of
358 C.J. Rodriguez-Ortiz et al. / Neurobiology of Learning and Memory 89 (2008) 352–359
both objects was impaired. However, when the same
objects were presented on both days anisomycin left mem-
ory unaltered. Similarly to the results described on the
present report, Morris et al. (2006) trained rats for 6 days
in the MWM task with the platform in a different position
on each day. On day 7, retrieval was accounted by a single
trial with the platform as on day 6, and anisomycin was
immediately injected. Under these conditions memory of
platform position on day 6 was impaired. On the other
hand, when platform location was kept constant during
the six training days, anisomycin injections after retrieval
on day 7 did not disrupt memory.
Tronel, Milekic, and Alberini (2005) reported that recon-
solidation and integration of new information to memory
are dissociable processes. They conditioned animals using
a light and a place as conditioned stimuli and a foot shock
as US. On the retrieval session, a new place (second CS)
and the same light were presented without the foot shock.
Therefore an association was established between the first
conditioning and the second CS, i.e. a second order condi-
tioning. They demonstrated that the transcription factor
CCAAT enhancer binding protein b (C/EBPb) is required
in the hippocampus for the second conditioning to be stored
in long-term memory. Conversely, when retrieval was
assessed presenting the same stimuli as in acquisition, C/
EBPb was required in the amygdala for memory to persist.
Thus, they concluded that reconsolidation requires protein
synthesis in one region and linking of new information
requires protein synthesis in another area, assuming that
these are two different processes. However, this interpreta-
tion must be taken carefully. Contrary to the above, we
observed that protein synthesis is required at least in the
same region every time memory is updated. Moreover, this
remains true even though updated information is of different
valence (Rodriguez-Ortiz et al., 2005, and this study).
With this latter model it can be argued that dissociable
cellular processes take place in the same region. However,
it seems that attention should be focused on the features
of the updated information, because these are the ones that
determine the cellular processes that would be undertaken.
That is, on their retrieval protocol Tronel et al. (2005) have
either the same or different (another context) information
as in acquisition. Integration of information of one kind
does not necessarily imply that integration of another kind
requires the same mechanisms. Even more, it seems intui-
tive that they do not. Behavior is not the same when inte-
gration of updated material strengthens the memory trace
as when it changes it. All in all, we consider that the
hypothesis that reconsolidation is indeed an updating con-
solidation is accumulating evidence and only further
research will allow that ultimately both notions, to our
view, come together.
Acknowledgments
We thank M. Mergol and B. Yahan for text review, and
Federico Jandete and Oreste Carbajal for technical assis-
tance. CONACYT-México 60478 and DGAPA-UNAM
IN212503 supported this study.
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