Efficacy of the Feliway® Classic Diffuser in reducing undesirable scratching in cats: A randomised, triple-blind, placebo-controlled study.

Scratching the environment is a natural behaviour that cats use for communication and physical maintenance purposes, however when it is carried out on household furniture it is considered unacceptable for some owners and even grounds for relinquishment of cats. The objective of this study was to investigate the efficacy of FELIWAY® Classic Diffuser in reducing undesirable scratching (scratching vertical surfaces indoors other than the scratching post) in cats. A 28 day, randomised, triple-blind, placebo-controlled study with a total of 1060 caregiver-cat dyads was conducted. The study contained two groups: the Pheromone Group consisted of caregivers who were given a pheromone diffuser (n = 546) and the Placebo Group consisted of caregivers who were given a placebo diffuser (n = 514). A questionnaire with three subsections was distributed online. The first section, completed by the respondents at day 0, inquired about the cats' daily routines, social and physical environments, behaviour, temperament, and emotional states. The second section filled on day 0, 7, 14, and 28, assessed the Frequency and the Intensity of the undesirable scratching problem and the effectiveness of the product. The last section, filled on the 28th day of the product application, related to the caregivers' opinions about the product and overall outcome. After 28 days the scratching Frequency reduced for 83.5% of the cats in the Pheromone Group and 68.5% for the Placebo Group (p<0.0001). The Intensity was significantly different between treatment groups at D7 (p = 0.0170), at D14 (p = 0.0189) and at D28 (p<0.001). The reduction of the Global Index Score, which was calculated by multiplying the Intensity with the Frequency, was significantly higher for the Pheromone Group (p<0.001). This study provides direct evidence that the use of FELIWAY® Classic diffuser significantly reduces the Frequency, Intensity and the Global Index Score of undesirable scratching.

Development of a Cat Behaviour Issues Assessment Scale (CABIAS) Assessing Problem Behaviours in Cats.

Problem behaviours in cats, such as urine marking, scratching, fear, and problems of cohabitation between cats, can present a potential welfare problem for those affected cats and have a negative impact on the human-animal bond. The aim of this study was to develop a Cat Behaviour Issues Assessment Scale (CABIAS) for caregivers to assess these common problem behaviours in cats, and to investigate aspects of the validity and reliability of the CABIAS. The CABIAS uses an index score as a scoring system combining aspects of the frequency and intensity of the problem behaviour. An electronic survey was developed, and 384 households, each with two participants able to observe the cat's behaviour, were recruited for the study. The participants were asked to record their cat's behaviour independently at weekly intervals over a 6-week period. A FELIWAY Optimum diffuser (containing a commercial feline pheromone complex) was provided to half of the participants, to be used during part of the study. The participants were subdivided into four groups according to whether a problem behaviour was present (or not) and whether the pheromone diffuser was provided (or not). The results demonstrated that the index scores for each problem behaviour had very high inter-rater reliability. There was a high correlation between the index scores and the impact the problem behaviours had on the caregivers. In those cats with a declared problem behaviour where the product was used, a reduction in index scores was observed over the duration of the study. The CABIAS was shown to exhibit satisfactory validity, reliability, and sensitivity to change in the current study, suggesting that it may be valuable as a tool for assessing and monitoring scratching, inter-cat cohabitation, urine marking, and fear in cats. The CABIAS could be used by veterinarians and behaviourists to assess these problem behaviours in individual cats and monitor responses to treatment. The CABIAS could also be considered as a research tool to assess the efficacy of interventions aimed at improving these problems.

Performance of Daily Pads Containing Ophytrium and Chlorhexidine Digluconate 3% in Dogs With Local Cutaneous Bacterial and/or Malassezia Overgrowth.

Local disturbances of the microbiota are common in dogs with underlying skin conditions. Antiseptic topical products are indicated to control such superficial disorders. The objective of this study was to evaluate the performance of a daily application of pads containing Ophytrium and chlorhexidine digluconate 3% (DOUXO® S3 PYO Pads, Ceva Santé Animale, France) in dogs with focal bacterial and/or Malassezia overgrowth. Eighteen dogs with focal skin dysbiosis were included in the analysis of this prospective, multicentric, field study. Dogs received daily pad applications for 14 days. Bacterial and/or Malassezia counts per microscopic field and a global score of the most affected patch (0-17 scale based on extension, severity, bacterial, and Malassezia cytological scores) were assessed by a veterinarian and pruritus by the owner (Pruritus Visual Analog Scale) on days (D)0, D7, D14. Owner and veterinarian evaluations for performance and satisfaction were recorded. Eleven dogs had primarily cocci overgrowth and seven mostly Malassezia. Mean bacterial and Malassezia counts decreased after 14 days (6.9-1.1; 7.6-1.5, respectively); 88.9% of dogs achieved a ≥70% microbial decrease and had ≤2 bacteria and ≤1 Malassezia per oil field. Mean global score of the most affected patch and pruritus score significantly improved at D14, respectively, from 8.6 to 2.6 and 4.5 to 1.2 (P < 0.05 each, mean improvements of 70.4 and 71.4%, respectively). Global veterinary assessment of the protocol was satisfactory, good, or excellent in 88.9% of cases. Most owners (94.4%) considered the protocol efficacious. Using a pad containing Ophytrium and chlorhexidine digluconate 3% daily for 14 days improved the skin condition and pruritus of dogs with local dysbiosis, resulting in high satisfaction levels for both veterinarians and dog owners.

Hyperactivity and attention deficits in mice with decreased levels of stress-inducible phosphoprotein 1 (STIP1).

Stress-inducible phosphoprotein I (STIP1, STI1 or HOP) is a co-chaperone intermediating Hsp70/Hsp90 exchange of client proteins, but it can also be secreted to trigger prion protein-mediated neuronal signaling. Some mothers of children with autism spectrum disorders (ASD) present antibodies against certain brain proteins, including antibodies against STIP1. Maternal antibodies can cross the fetus blood-brain barrier during pregnancy, suggesting the possibility that they can interfere with STIP1 levels and, presumably, functions. However, it is currently unknown whether abnormal levels of STIP1 have any impact in ASD-related behavior. Here, we used mice with reduced (50%) or increased STIP1 levels (fivefold) to test for potential ASD-like phenotypes. We found that increased STIP1 regulates the abundance of Hsp70 and Hsp90, whereas reduced STIP1 does not affect Hsp70, Hsp90 or the prion protein. Interestingly, BAC transgenic mice presenting fivefold more STIP1 show no major phenotype when examined in a series of behavioral tasks, including locomotor activity, elevated plus maze, Morris water maze and five-choice serial reaction time task (5-CSRTT). In contrast, mice with reduced STIP1 levels are hyperactive and have attentional deficits on the 5-CSRTT, but exhibit normal performance for the other tasks. We conclude that reduced STIP1 levels can contribute to phenotypes related to ASD. However, future experiments are needed to define whether it is decreased chaperone capacity or impaired prion protein signaling that contributes to these phenotypes.

Characterization of spatial memory reconsolidation.

Reconsolidation is necessary for the restabilization of reactivated memory traces. However, experimental parameters have been suggested as boundary conditions for this process. Here we investigated the role of a spatial memory trace's age, strength, and update on the reconsolidation process in mice. We first found that protein synthesis is necessary for reconsolidation to occur in the hippocampal CA3 region after reactivation of partially acquired and old memories but not for strongly acquired and recent memories. We also demonstrated that the update of a previously stable memory required, again, a memory reconsolidation in the hippocampal CA3. Finally, we found that the reactivation of a strongly acquired memory requires an activation of the anterior cingulate cortex as soon as 24 h after acquisition. This study demonstrates the importance of the knowledge of the task on the dynamic nature of memory reconsolidation processing.

Photobiomodulation inside the brain: a novel method of applying near-infrared light intracranially and its impact on dopaminergic cell survival in MPTP-treated mice.

OBJECT: Previous experimental studies have documented the neuroprotection of damaged or diseased cells after applying, from outside the brain, near-infrared light (NIr) to the brain by using external light-emitting diodes (LEDs) or laser devices. In the present study, the authors describe an effective and reliable surgical method of applying to the brain, from inside the brain, NIr to the brain. They developed a novel internal surgical device that delivers the NIr to brain regions very close to target damaged or diseased cells. They suggest that this device will be useful in applying NIr within the large human brain, particularly if the target cells have a very deep location. METHODS: An optical fiber linked to an LED or laser device was surgically implanted into the lateral ventricle of BALB/c mice or Sprague-Dawley rats. The authors explored the feasibility of the internal device, measured the NIr signal through living tissue, looked for evidence of toxicity at doses higher than those required for neuroprotection, and confirmed the neuroprotective effect of NIr on dopaminergic cells in the substantia nigra pars compacta (SNc) in an acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson disease in mice. RESULTS: The device was stable in freely moving animals, and the NIr filled the cranial cavity. Measurements showed that the NIr intensity declined as distance from the source increased across the brain (65% per mm) but was detectable up to 10 mm away. At neuroprotective (0.16 mW) and much higher (67 mW) intensities, the NIr caused no observable behavioral deficits, nor was there evidence of tissue necrosis at the fiber tip, where radiation was most intense. Finally, the intracranially delivered NIr protected SNc cells against MPTP insult; there were consistently more dopaminergic cells in MPTP-treated mice irradiated with NIr than in those that were not irradiated. CONCLUSIONS: In summary, the authors showed that NIr can be applied intracranially, does not have toxic side effects, and is neuroprotective.

Opiate exposure and withdrawal induces a molecular memory switch in the basolateral amygdala between ERK1/2 and CaMKIIα-dependent signaling substrates.

Opiate reward memories are powerful triggers for compulsive opiate-seeking behaviors. The basolateral amygdala (BLA) is an important structure for the processing of opiate-related associative memories and is functionally linked to the mesolimbic dopamine (DA) pathway. Transmission through intra-BLA DA D1-like and D2-like receptors independently modulates the formation of opiate reward memories as a function of opiate-exposure state. Thus, in the opiate-naive state, intra-BLA D1 transmission is required for opiate-related memory formation. Once opiate dependence and withdrawal has developed, a functional switch to a DA D2-mediated memory mechanism takes place. However, the downstream molecular signaling events that control this functional switch between intra-BLA DA D1 versus D2 receptor transmission are not currently understood. Using an unbiased place conditioning procedure in rats combined with molecular analyses, we report that opiate reward memory acquisition requires intra-BLA ERK1/2 signaling only in the previously opiate-naive state. However, following chronic opiate exposure and withdrawal, intra-BLA reward memory processing switches to a CaMKIIα-dependent memory substrate. Furthermore, the ability of intra-BLA DA D1 or D2 receptor transmission to modulate the motivational salience of opiates similarly operates through a D1-mediated ERK-dependent mechanism in the opiate-naive state, but switches to a D2-mediated CaMKIIα-dependent mechanism in the dependent/withdrawn state. Protein analysis of BLA tissue revealed a downregulation of ERK1/2 phosphorylation and a dramatic reduction in both total and phosphorylated CaMKIIα signaling, specifically in the opiate-dependent/withdrawn state, demonstrating functional control of ERK1/2-dependent versus CaMKIIα-dependent memory mechanisms within the BLA, controlled by opiate-exposure state.

Cannabinoid transmission in the prelimbic cortex bidirectionally controls opiate reward and aversion signaling through dissociable kappa versus µ-opiate receptor dependent mechanisms.

Cannabinoid, dopamine (DA), and opiate receptor pathways play integrative roles in emotional learning, associative memory, and sensory perception. Modulation of cannabinoid CB1 receptor transmission within the medial prefrontal cortex (mPFC) regulates the emotional valence of both rewarding and aversive experiences. Furthermore, CB1 receptor substrates functionally interact with opiate-related motivational processing circuits, particularly in the context of reward-related learning and memory. Considerable evidence demonstrates functional interactions between CB1 and DA signaling pathways during the processing of motivationally salient information. However, the role of mPFC CB1 receptor transmission in the modulation of behavioral opiate-reward processing is not currently known. Using an unbiased conditioned place preference paradigm with rats, we examined the role of intra-mPFC CB1 transmission during opiate reward learning. We report that activation or inhibition of CB1 transmission within the prelimbic cortical (PLC) division of the mPFC bidirectionally regulates the motivational valence of opiates; whereas CB1 activation switched morphine reward signaling into an aversive stimulus, blockade of CB1 transmission potentiated the rewarding properties of normally sub-reward threshold conditioning doses of morphine. Both of these effects were dependent upon DA transmission as systemic blockade of DAergic transmission prevented CB1-dependent modulation of morphine reward and aversion behaviors. We further report that CB1-mediated intra-PLC opiate motivational signaling is mediated through a µ-opiate receptor-dependent reward pathway, or a κ-opiate receptor-dependent aversion pathway, directly within the ventral tegmental area. Our results provide evidence for a novel CB1-mediated motivational valence switching mechanism within the PLC, controlling dissociable subcortical reward and aversion pathways.

Early versus late-phase consolidation of opiate reward memories requires distinct molecular and temporal mechanisms in the amygdala-prefrontal cortical pathway.

The consolidation of newly acquired memories involves the temporal transition from a recent, less stable trace to a more permanent consolidated form. Opiates possess potent rewarding effects and produce powerful associative memories. The activation of these memories is associated with opiate abuse relapse phenomena and the persistence of compulsive opiate dependence. However, the neuronal, molecular and temporal mechanisms by which associative opiate reward memories are consolidated are not currently understood. We report that the consolidation of associative opiate reward memories involves a temporal and molecular switch between the basolateral nucleus of the amygdala (BLA) (early consolidation phase) to the medial prefrontal cortex (mPFC) (late consolidation phase). We demonstrate at the molecular, behavioral and neuronal levels that the consolidation of a recently acquired opiate reward memory involves an extracellular signal-related kinase (ERK)-dependent phosphorylation process within the BLA. In contrast, later-stage consolidation of a newly acquired memory is dependent upon a calcium-calmodulin-dependent (CaMKII), ERK-independent, mechanism in the mPFC, over a 12 hr temporal gradient. In addition, using in vivo multi-unit neuronal recordings in the mPFC, we report that protein synthesis within the BLA modulates the consolidation of opiate-reward memory in neuronal mPFC sub-populations, via the same temporal dynamic.

The effects of AMPA receptor blockade in the prelimbic cortex on systemic and ventral tegmental area opiate reward sensitivity.

RATIONALE: The medial prefrontal cortex (mPFC) is a key neural region involved in opiate-related reward memory processing. AMPA receptor transmission in the mPFC modulates opiate-related reward memory processing, and chronic opiate exposure is associated with alterations in intra-mPFC AMPA receptor function. OBJECTIVE: The objectives of this study were to examine how pharmacological blockade of AMPA receptor transmission in the prelimbic (PLC) division of the mPFC may modulate opiate reward memory acquisition and whether opiate exposure state may modulate the functional role of intra-PLC AMPA receptor transmission during opiate reward learning. METHODS: Using an unbiased conditioned place preference (CPP) procedure in rats, we performed discrete, bilateral intra-PLC microinfusions of the AMPA receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione, prior to behavioral morphine CPP conditioning, using sub-reward threshold conditioning doses of either systemic (0.05 mg/kg; i.p.) or intra-ventral tegmental area (VTA) morphine (250 ng/0.5 µl). RESULTS: We show that, in both opiate-naïve and opiate-dependent states, intra-PLC blockade of AMPA receptor transmission, but not the infralimbic cortex, increases the behavioral reward magnitude of systemic or intra-VTA morphine. This effect is dependent on dopamine (DA)ergic signaling because pre-administration of cis-(Z)-flupenthixol-dihydrochloride (α-flu), a broad-spectrum dopamine receptor antagonist, blocked the morphine-reward potentiating effects of AMPA receptor blockade. CONCLUSIONS: These findings suggest a critical role for intra-PLC AMPA receptor transmission in the processing of opiate reward signaling. Furthermore, blockade of AMPA transmission specifically within the PLC is capable of switching opiate reward processing to a DA-dependent reward system, independently of previous opiate exposure history.

Mice with selective elimination of striatal acetylcholine release are lean, show altered energy homeostasis and changed sleep/wake cycle.

Cholinergic neurons are known to regulate striatal circuits; however, striatal-dependent physiological outcomes influenced by acetylcholine (ACh) are still poorly under;?>stood. Here, we used vesicular acetylcholine transporter (VAChT)(D2-Cre-flox/flox) mice, in which we selectively ablated the vesicular acetylcholine transporter in the striatum to dissect the specific roles of striatal ACh in metabolic homeostasis. We report that VAChT(D) (2-Cre-flox/flox) mice are lean at a young age and maintain this lean phenotype with time. The reduced body weight observed in these mutant mice is not attributable to reduced food intake or to a decrease in growth rate. In addition, changed activity could not completely explain the lean phenotype, as only young VAChT(D) (2-Cre-flox/flox) mice showed increased physical activity. Interestingly, VAChT(D) (2-Cre-flox/flox) mice show several metabolic changes, including increased plasma levels of insulin and leptin. They also show increased periods of wakefulness when compared with littermate controls. Taken together, our data suggest that striatal ACh has an important role in the modulation of metabolism and highlight the importance of striatum cholinergic tone in the regulation of energy expenditure. These new insights on how cholinergic neurons influence homeostasis open new avenues for the search of drug targets to treat obesity.

Decreased acetylcholine release delays the consolidation of object recognition memory.

Acetylcholine (ACh) is important for different cognitive functions such as learning, memory and attention. The release of ACh depends on its vesicular loading by the vesicular acetylcholine transporter (VAChT). It has been demonstrated that VAChT expression can modulate object recognition memory. However, the role of VAChT expression on object recognition memory persistence still remains to be understood. To address this question we used distinct mouse lines with reduced expression of VAChT, as well as pharmacological manipulations of the cholinergic system. We showed that reduction of cholinergic tone impairs object recognition memory measured at 24h. Surprisingly, object recognition memory, measured at 4 days after training, was impaired by substantial, but not moderate, reduction in VAChT expression. Our results suggest that levels of acetylcholine release strongly modulate object recognition memory consolidation and appear to be of particular importance for memory persistence 4 days after training.

Elimination of the vesicular acetylcholine transporter in the forebrain causes hyperactivity and deficits in spatial memory and long-term potentiation.

Basal forebrain cholinergic neurons, which innervate the hippocampus and cortex, have been implicated in many forms of cognitive function. Immunolesion-based methods in animal models have been widely used to study the role of acetylcholine (ACh) neurotransmission in these processes, with variable results. Cholinergic neurons have been shown to release both glutamate and ACh, making it difficult to deduce the specific contribution of each neurotransmitter on cognition when neurons are eliminated. Understanding the precise roles of ACh in learning and memory is critical because drugs that preserve ACh are used as treatment for cognitive deficits. It is therefore important to define which cholinergic-dependent behaviors could be improved pharmacologically. Here we investigate the contributions of forebrain ACh on hippocampal synaptic plasticity and cognitive behavior by selective elimination of the vesicular ACh transporter, which interferes with synaptic storage and release of ACh. We show that elimination of vesicular ACh transporter in the hippocampus results in deficits in long-term potentiation and causes selective deficits in spatial memory. Moreover, decreased cholinergic tone in the forebrain is linked to hyperactivity, without changes in anxiety or depression-related behavior. These data uncover the specific contribution of forebrain cholinergic tone for synaptic plasticity and behavior. Moreover, these experiments define specific cognitive functions that could be targeted by cholinergic replacement therapy.

Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission.

Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.

Novel strains of mice deficient for the vesicular acetylcholine transporter: insights on transcriptional regulation and control of locomotor behavior.

Defining the contribution of acetylcholine to specific behaviors has been challenging, mainly because of the difficulty in generating suitable animal models of cholinergic dysfunction. We have recently shown that, by targeting the vesicular acetylcholine transporter (VAChT) gene, it is possible to generate genetically modified mice with cholinergic deficiency. Here we describe novel VAChT mutant lines. VAChT gene is embedded within the first intron of the choline acetyltransferase (ChAT) gene, which provides a unique arrangement and regulation for these two genes. We generated a VAChT allele that is flanked by loxP sequences and carries the resistance cassette placed in a ChAT intronic region (FloxNeo allele). We show that mice with the FloxNeo allele exhibit differential VAChT expression in distinct neuronal populations. These mice show relatively intact VAChT expression in somatomotor cholinergic neurons, but pronounced decrease in other cholinergic neurons in the brain. VAChT mutant mice present preserved neuromuscular function, but altered brain cholinergic function and are hyperactive. Genetic removal of the resistance cassette rescues VAChT expression and the hyperactivity phenotype. These results suggest that release of ACh in the brain is normally required to "turn down" neuronal circuits controlling locomotion.

The vesicular acetylcholine transporter is required for neuromuscular development and function.

The vesicular acetylcholine (ACh) transporter (VAChT) mediates ACh storage by synaptic vesicles. However, the VAChT-independent release of ACh is believed to be important during development. Here we generated VAChT knockout mice and tested the physiological relevance of the VAChT-independent release of ACh. Homozygous VAChT knockout mice died shortly after birth, indicating that VAChT-mediated storage of ACh is essential for life. Indeed, synaptosomes obtained from brains of homozygous knockouts were incapable of releasing ACh in response to depolarization. Surprisingly, electrophysiological recordings at the skeletal-neuromuscular junction show that VAChT knockout mice present spontaneous miniature end-plate potentials with reduced amplitude and frequency, which are likely the result of a passive transport of ACh into synaptic vesicles. Interestingly, VAChT knockouts exhibit substantial increases in amounts of choline acetyltransferase, high-affinity choline transporter, and ACh. However, the development of the neuromuscular junction in these mice is severely affected. Mutant VAChT mice show increases in motoneuron and nerve terminal numbers. End plates are large, nerves exhibit abnormal sprouting, and muscle is necrotic. The abnormalities are similar to those of mice that cannot synthesize ACh due to a lack of choline acetyltransferase. Our results indicate that VAChT is essential to the normal development of motor neurons and the release of ACh.

Protein degradation, as with protein synthesis, is required during not only long-term spatial memory consolidation but also reconsolidation.

The formation of long-term memory requires protein synthesis, particularly during initial memory consolidation. This process also seems to be dependant upon protein degradation, particularly degradation by the ubiquitin-proteasome system. The aim of this study was to investigate the temporal requirement of protein synthesis and degradation during the initial consolidation of allocentric spatial learning. As memory returns to a labile state during reactivation, we also focus on the role of protein synthesis and degradation during memory reconsolidation of this spatial learning. Male CD1 mice were submitted to massed training in the spatial version of the Morris water maze. At various time intervals after initial acquisition or after a reactivation trial taking place 24 h after acquisition, mice received an injection of either the protein synthesis inhibitor anisomycin or the protein degradation inhibitor lactacystin. This injection was performed into the hippocampal CA3 region, which is specifically implicated in the processing of spatial information. Results show that, in the CA3 hippocampal region, consolidation of an allocentric spatial learning task requires two waves of protein synthesis taking place immediately and 4 h after acquisition, whereas reconsolidation requires only the first wave. However, for protein degradation, both consolidation and reconsolidation require only one wave, taking place immediately after acquisition or reactivation, respectively. These findings suggest that protein degradation is a key step for memory reconsolidation, as for consolidation. Moreover, as protein synthesis-dependent reconsolidation occurred faster than consolidation, reconsolidation did not consist of a simple repetition of the initial consolidation.

Reactivation with a simple exposure to the experimental environment is sufficient to induce reconsolidation requiring protein synthesis in the hippocampal CA3 region in mice.

Our understanding of the memory reconsolidation process is at an earlier stage than that of consolidation. For example, it is unclear if, as for memory consolidation, reconsolidation of a memory trace necessitates protein synthesis. In fact, conflicting results appear in the literature and this discrepancy may be due to differences in the experimental reactivation procedure. Here, we addressed the question of whether protein synthesis in the CA3 hippocampal region is crucial in memory consolidation and reconsolidation of allocentric knowledge after reactivation in different experimental conditions in the Morris water maze. We showed (1) that an injection of the protein synthesis inhibitor anisomycin in the CA3 region during consolidation or after a single reactivation trial disrupted performance and (2) that protein synthesis is required even after a simple contextual reactivation without any learning trial and independently of the presence of the reinforcement. This work demonstrates that a simple exposure to the spatial environment is sufficient to reactivate the memory trace, to make it labile, and that reconsolidation of this trace requires de novo protein synthesis.