Memory In Rodents Research Articles

Fear Expression Suppresses Medial Prefrontal Cortical Firing in Rats.

The medial prefrontal cortex (mPFC) plays a crucial role in emotional learning and memory in rodents and humans. While many studies suggest a differential role for the prelimbic (PL) and infralimbic (IL) subdivisions of mPFC, few have considered the relationship between neural activity in these two brain regions recorded simultaneously in behaving animals. Importantly, how concurrent PL and IL activity relate to conditioned freezing behavior is largely unknown. Here we used single-unit recordings targeting PL and IL in awake, behaving rats during the acquisition and expression of conditioned fear. On Day 1, rats received either signaled or unsignaled footshocks in the recording chamber; an auditory conditioned stimulus (CS) preceded signaled footshocks. Twenty-four hours later, animals were returned to the recording chamber (modified to create a novel context) where they received 5 CS-alone trials. After fear conditioning, both signaled and unsignaled rats exhibited high levels of post-shock freezing that was associated with an enduring suppression of mPFC spontaneous firing, particularly in the IL of signaled rats. Twenty-four hours later, CS presentation produced differential conditioned freezing in signaled and unsignaled rats: freezing increased in rats that had received signaled shocks, but decreased in animals in the unsignaled condition (i.e., external inhibition). This group difference in CS-evoked freezing was mirrored in the spontaneous firing rate of neurons in both PL and IL. Interestingly, differences in PL and IL firing rate highly correlated with freezing levels. In other words, in the signaled group IL spontaneous rates were suppressed relative to PL, perhaps limiting IL-mediated suppression of fear and allowing PL activity to dominate performance, resulting in high levels of freezing. This was not observed in the unsignaled group, which exhibited low freezing. These data reveal that the activity of mPFC neurons is modulated by both associative and nonassociative stimuli that regulate conditioned fear.

A small molecule targeting protein translation does not rescue spatial learning and memory deficits in the hAPP-J20 mouse model of Alzheimer's disease.

A small molecule named ISRIB has recently been described to enhance memory in rodents. In this study we aimed to test whether ISRIB would reverse learning and memory deficits in the J20 mouse model of human amyloid precursor protein (hAPP) overexpression, a model that simulates many aspects of Alzheimer’s disease in which memory deficits are a hallmark feature. We did not observe a significant rescue effect with ISRIB treatment on spatial learning and memory as assessed in the Morris water maze in J20 mice. We also did not observe a significant enhancement of spatial learning or memory in nontransgenic mice with ISRIB treatment, although a trend emerged for memory enhancement in one cohort of mice. Future preclinical studies with ISRIB would benefit from additional robust markers of target engagement in the brain.

The use of the Emotional-Object Recognition as an assay to assess learning and memory associated to an aversive stimulus in rodents

BackgroundEmotionally salient experiences induce the formation of explicit memory traces, besides eliciting automatic or implicit emotional memory in rodents. This study aims at investigating the implementation of a novel task for studying the formation of limbic memory engrams as a result of the acquisition- and retrieval- of fear-conditioning – biased declarative memory traces, measured by animal discrimination of an “emotional-object”. Moreover, by using this new method we investigated the potential interactions between stimulation of cannabinoid transmission and integration of emotional information and cognitive functioning. New methodThe Emotional-Object Recognition task is composed of 3 following sessions: habituation; cued fear-conditioned learning; emotional recognition. Rats are exposed to Context “B chamber” for habituation and cued fear-conditioning, and tested in Context “A chamber” for emotional-object recognition. ResultsCued fear-conditioning induces a reduction in emotional-object exploration time during the Emotional-Object Recognition task in controls. The activation of cannabinoid signalling impairs limbic memory formation, with respect to vehicle. Comparison to existing methodsThe Emotional-Object Recognition test overcomes several limitations of commonly employed methods that explore declarative-, spatial memory and fear-conditioning in a non-integrated manner. It allows the assessment of unbiased cognitive indicators of emotional learning and memory. ConclusionsThe Emotional-Object Recognition task is a valuable tool for investigating whether, and at what extent, specific drugs or pathological conditions that interfere with the individual affective/emotional homeostasis, can modulate the formation of emotionally salient explicit memory traces, thus jeopardizing control and regulation of animal behavioural strategy.

Hippocampal GluA2 and GluA4 protein but not corresponding mRNA and promoter methylation levels are modulated at retrieval in spatial learning of the rat.

AMPA receptors mediate most fast excitatory synaptic transmission in the brain. Highly dynamic AMPA receptors are subjected to trafficking, recycling, and/or degradation and replacement. Changes in AMPA receptor abundance is an important mechanism involved in learning and memory formation. Results obtained with the Morris water maze (MWM), a paradigm for testing spatial memory in rodent, correlate with hippocampal synaptic plasticity and NMDA function. Different phases of spatial learning like acquisition and retrieval involve AMPA receptors. Long-term memory formation requires dynamic changes in gene transcription and protein synthesis. It is, however, not known so far if epigenetic marks such as DNA methylation and mRNA levels participate in regulation of AMPA receptors in hippocampus during memory retrieval. In the present study, rats were trained or untrained in the MWM. Steady state levels of hippocampal GluA1-4 mRNA were determined by RT-PCR and promoter methylation levels of GluA1-4 by in-house developed bisulfite pyrosequencing methods. GluA1-4 protein levels were determined in parallel in a membrane fraction by SDS-PAGE followed by Western blotting. Our results indicate that changes of hippocampal membrane AMPA receptors were modulated at the protein level, while no changes were observed at the mRNA and at the promoter methylation level of hippocampal GluA1-4. Training in the MWM at retrieval may, therefore, involve GluA2 and GluA4 subunits that may be regulated by protein stability or trafficking as protein determinations were carried out in a hippocampal membrane fraction.

Forebrain neurone-specific deletion of insulin-regulated aminopeptidase causes age related deficits in memory

Central infusion of Insulin-Regulated Aminopeptidase (IRAP) inhibitors improves memory in both normal rodents and in models of memory deficit. However, in contrast, the global IRAP knockout mice (KO) demonstrate age-accelerated spatial memory deficits and no improvements in performance in any memory tasks. Potentially, the observed memory deficit could be due to the absence of IRAP in the developing brain. We therefore generated a postnatal forebrain neuron-specific IRAP knockout mouse line (CamKIIalphaCre; IRAPlox/lox). Unexpectedly, we demonstrated that postnatal deletion of IRAP in the brain results in significant deficits in both spatial reference and object recognition memory at three months of age, although spatial working memory remained intact. These results indicate a significant role for IRAP in postnatal brain development and normal function of the hippocampus in adulthood.

Impact of Chronic Stress Protocols in Learning and Memory in Rodents: Systematic Review and Meta-Analysis.

The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals’ strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests’ performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments.

Influence of Proximal, Distal, and Vestibular Frames of Reference in Object-Place Paired Associate Learning in the Rat.

Object-place paired associate learning has been used to test hypotheses regarding the neurobiological basis of memory in rodents. Much of this work has focused on the role of limbic and hippocampal-parahippocampal regions, as well as the use of spatial information derived from allothetic visual stimuli to determine location in an environment. It has been suggested that idiothetic self-motion (vestibular) signals and internal representations of directional orientation might play an important role in disambiguating between spatial locations when forming object-place associations, but this hypothesis has not been explicitly tested. In the present study, we investigated the relationship between allothetic (i.e., distal and proximal cues) and vestibular stimuli on performance of an object-place paired-associate task. The paired-associate task was composed of learning to discriminate between an identical pair of objects presented in 180° opposite arms of a radial arm maze. Thus, animals were required to select a particular object on the basis of spatial location (i.e., maze arm). After the animals acquired the object-place rule, a series of probe tests determined that rats utilize self-generated vestibular cues to discriminate between the two maze arms. Further, when available, animals showed a strong preference for local proximal cues associated with the maze. Together, the work presented here supports the establishment of an object-place task that requires both idiothetic and allothetic stimulus sources to guide choice behavior, and which can be used to further investigate the dynamic interactions between neural systems involved in pairing sensory information with spatial locations.

Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine.

BackgroundPhosphatidylcholine (PC), the major source of dietary choline, has been demonstrated to improve the capability of learning and memory in rodent and the amelioration of long-chain n-3 polyunsaturated fatty acids (PUFA) on anti-aging and anti-oxidation is widely known as well. In this study, three kinds of PC were chose to demonstrate the role of different fatty acids composition on glycerol backbone in improving the brain function of mice induced by scopolamine which was used to impair cholinergic system and cause oxidative stress.MethodsMale BALB/c mice were randomly divided into 5 groups: model (M) group, control (Con) group, egg yolk lecithin (EL) group, squid PC (SQ-PC) group and sea cucumber PC (SC-PC) group. The intraperitoneal injection of scopolamine hydrobromide (5 mg/kg) was carried out on the 8th of group feeding and sustained daily until the end of test. Morris water maze test was used to evaluate the improvement of cognitive decline and the activity of acetylcholinesterase (AchE), superoxide dismutase (SOD) and monoamine oxidase (MAO) and malondialdehyde (MDA) content in brain were measured to assess the physiological changes.ResultsIn behavior test, the latency of PC groups was significantly reduced, while number of crossing the platform and time in target quadrant were increased in comparison with M group and the improvements of SQ-PC and SC-PC were better than that of EL (P < 0.05). Similar trend was observed in physiological changes. The AchE activity was effectively decreased and the SOD activity increased in hippocampus, cortex and white matter when comparing PC groups with M group. SQ-PC, SC-PC and EL respectively showed 22.82, 28.80 and 11.81 % decrease in MDA level in brain compared with M group. The MAO activity in white matter of SQ-PC, SC-PC and EL group separately depressed 33.05, 33.64 and 19.73 % in comparison with M group. No significance between SQ-PC and SC-PC was found in these indicators except the SOD activity in hippocampus and white matter. SQ-PC group had a higher SOD activity in hippocampus (103.68U/mg · prot.) and lower in white matter (120.57 U/mg · prot.) than SC-PC group (95.53 U/mg · prot. in hippocampus, 134.49 U/mg · prot. in white matter). PC rich in n-3 PUFA acted more ameliorative effects than that barely contained on the indicators above.ConclusionsDifferent fatty acids composition of PC all could diminish the cognitive decline and biological damage and protect the brain. EPA and DHA partly enhaced to the advantageous effects.

The Amygdala and Prioritization of Declarative Memories

The present review highlights results from recent studies that delivered brief electrical stimulation to the basolateral complex of the amygdala in rats to reveal its capacity to prioritize declarative memories on a moment-to-moment basis even after the moment has passed. The results indicate that this memory enhancement depends on the hippocampus and elicits intrahippocampal gamma synchrony that possibly corresponds with sharpened hippocampal spike-timing dependent plasticity. These recent findings are discussed in relation to past studies of emotional memory in rodents and humans.

Effects of the cannabinoid 1 receptor peptide ligands hemopressin, (m)RVD-hemopressin(α) and (m)VD-hemopressin(α) on memory in novel object and object location recognition tasks in normal young and Aβ1–42-treated mice

The cannabinoid system plays an important role in memory processes, many studies have indicated that cannabinoid receptor ligands have ability to modulate memory in rodents. A nonapeptide hemopressin (Hp) derived from rat brain, acts as a peptide antagonist or selective inverse peptide agonist of cannabinoid 1 (CB1) receptor. N-terminally extended forms of Hp isolated from mouse brain, (m)RVD-hemopressin(α) (RVD) and (m)VD-hemopressin(α) (VD) also bind CB1 receptor, however, as peptide agonists. Here, we investigated the roles of Hp, RVD, and VD on memory in mice using novel object recognition (NOR) and object location recognition (OLR) tasks.In normal young mice, intracerebroventricular (i.c.v.) infusion of Hp before training not only improved memory formation, but also prolonged memory retention in the tasks, these effects could be inhibited by RVD or VD at the same dose and intraperitoneal (i.p.) injection of a small molecule agonist of CB1 receptor WIN55, 212-2 15min before administration of Hp inhibited the memory-improving effect of Hp. In addition, under the same experimental conditions, i.c.v. RVD or VD displayed memory-impairing effects, which could be prevented by Hp (i.c.v.) or AM251 (i.p.), a small molecule antagonist of CB1 receptor.Infusion of amyloid-β (1–42) (Aβ1–42) 14days before training resulted in impairment of memory in mice which could be used as animal model of Alzheimer’s disease (AD). In these mice, RVD or VD (i.c.v.) reversed the memory impairment induced by Aβ1–42, and the effects of RVD and VD could be suppressed by Hp (i.c.v.) or AM251 (2mg/kg, i.p.). Separate administration of Hp had no effect in Aβ1–42-treated mice.The above results suggested that Hp, RVD and VD, as CB1 receptor peptide ligands, may be potential drugs to treatment of the memory deficit-involving disease, just as AD.

Relevance of Test- and Subject-Related Factors on Inhibitory Avoidance (Performance) of Zebrafish for Psychopharmacology Studies

Background: The inhibitory (or passive) avoidance paradigm is widely used to assess the effects of drugs on emotion, learning and memory in rodents. The zebrafish is gaining more and more popularity as an animal model in, among others, psychopharmacological research. In zebrafish, inhibitory avoidance is also used as assay to assess the effects of drugs and other treatments on fear-associated learning. The inhibitory avoidance paradigm is based on the conflict between (i) the innate response to enter a dark area to avoid a brightly lit area (scototaxis) and (ii) avoiding exposure to a shock in the dark area, i.e. contextual (shock-environment) fear-learning. Objective: This review summarises recent studies that characterised different features of the inhibitory avoidance paradigm. This knowledge is necessary to fully appreciate drug-related effects in this task. Results: These studies have revealed factors that affect performance of zebrafish in the task, e.g. test-related parameters (such as shock intensity) and subject-characteristics at the time of testing (including age, strain and rearing conditions). In addition, they allowed generating hypotheses on physiological and genetic mechanisms underlying inhibitory avoidance in zebrafish. Conclusion: The inhibitory avoidance assay is a useful research tool to study emotion, learning and memory in zebrafish. Directions for future research are indicated, which may further optimise the use of the inhibitory avoidance assay in zebrafish as research tool. Keywords: Zebrafish, inhibitory avoidance, fear learning, memory, genetics, physiology.

Unbiased classification of spatial strategies in the Barnes maze.

Spatial learning is one of the most widely studied cognitive domains in neuroscience. The Morris water maze and the Barnes maze are the most commonly used techniques to assess spatial learning and memory in rodents. Despite the fact that these tasks are well-validated paradigms for testing spatial learning abilities, manual categorization of performance into behavioral strategies is subject to individual interpretation, and thus to bias. We have previously described an unbiased machine-learning algorithm to classify spatial strategies in the Morris water maze. Here, we offer a support vector machine-based, automated, Barnes-maze unbiased strategy (BUNS) classification algorithm, as well as a cognitive score scale that can be used for memory acquisition, reversal training and probe trials. The BUNS algorithm can greatly benefit Barnes maze users as it provides a standardized method of strategy classification and cognitive scoring scale, which cannot be derived from typical Barnes maze data analysis. Freely available on the web at http://okunlab.wix.com/okunlab as a MATLAB application. eitan.okun@biu.ac.ilSupplementary information: Supplementary data are available at Bioinformatics online.

In search of the memory molecule

The protein PKM-ζ has been proposed to regulate the maintenance of memory in rodents, but this theory has been questioned. The finding that another isoform of the protein acts as a backup if PKM-ζ is lacking will influence this debate.

The anterior versus posterior hippocampal oscillations debate in human spatial navigation: evidence from an electrocorticographic case study.

IntroductionHippocampal oscillations have been regularly described as playing a dominant role in spatial memory and navigation in rodents. In humans, the relative role of anterior versus posterior rhythms during navigational memory is not established.MethodsHere, we tested this hypothesis using direct brain ECoG recordings in the anterior and posterior hippocampus of a patient, in a navigational task requiring spatial memory. We assessed multiple oscillatory bands during encoding and retrieval phases.ResultsWe found navigation related 1–3.5 Hz activity during retrieval, both in the anterior and posterior hippocampus. Activity between 4 and 8 Hz was identified during both encoding and retrieval, only in the anterior hippocampus.ConclusionsOur findings are consistent with the view that an anterior/posterior functional gradient is present in the hippocampus, and involves two distinct neuronal networks, supporting either encoding or retrieval processes. Although this is a single case scenario, these findings suggest that neural oscillations during spatial navigation do vary across hippocampal subregions, as a function of encoding versus retrieval processes during the mnemonic process. In this single case study, the results point to the presence of a dual involvement of multiple frequency bands across hippocampal subregions during encoding and retrieval. Although these results need generalization, they provide a new perspective on distinct physiological properties of the anterior and posterior hippocampus in human spatial navigation during encoding and retrieval.

Guppies Show Behavioural but Not Cognitive Sex Differences in a Novel Object Recognition Test

The novel object recognition (NOR) test is a widely-used paradigm to study learning and memory in rodents. NOR performance is typically measured as the preference to interact with a novel object over a familiar object based on spontaneous exploratory behaviour. In rats and mice, females usually have greater NOR ability than males. The NOR test is now available for a large number of species, including fish, but sex differences have not been properly tested outside of rodents. We compared male and female guppies (Poecilia reticulata) in a NOR test to study whether sex differences exist also for fish. We focused on sex differences in both performance and behaviour of guppies during the test. In our experiment, adult guppies expressed a preference for the novel object as most rodents and other species do. When we looked at sex differences, we found the two sexes showed a similar preference for the novel object over the familiar object, suggesting that male and female guppies have similar NOR performances. Analysis of behaviour revealed that males were more inclined to swim in the proximity of the two objects than females. Further, males explored the novel object at the beginning of the experiment while females did so afterwards. These two behavioural differences are possibly due to sex differences in exploration. Even though NOR performance is not different between male and female guppies, the behavioural sex differences we found could affect the results of the experiments and should be carefully considered when assessing fish memory with the NOR test.

Erythrocyte intracellular Mg(2+) concentration as an index of recognition and memory.

Magnesium (Mg2+) plays an important role in the neural system, and yet scarcely any research has quantitatively analyzed the link between endogenous Mg2+ level and memory. Using our original technique, we measured erythrocyte intracellular ionized Mg2+ concentration (RBC [Mg2+]i), which linearly correlated to recognition and spatial memory in normal aging rats. In the brain, RBC [Mg2+]i significantly correlated to hippocampus extracellular fluid Mg2+ concentration, and further correlated to hippocampal synapse density. Elevation of Mg2+ intake in aged rats demonstrated an association between RBC [Mg2+]i increase and memory recovery. The therapeutic effect of Mg2+ administration was inversely correlated to individual basal RBC [Mg2+]i. In summary, we provide a method to measure RBC [Mg2+]i, an ideal indicator of body Mg2+ level. RBC [Mg2+]i represents rodent memory performance in our study, and might further serve as a potential biomarker for clinical differential diagnosis and precise treatment of Mg2+-deficiency-associated memory decline during aging.

Conducting and automating Morris water maze test under SPF conditions

The Morris water maze is the basic test to study spatial learning and memory in laboratory rodents. It is part of the set of tests necessary for behavioral phenotyping of mutant and transgenic mice. However, the SPF conditions impose very strict regulations on pathogen control, which hinders performance of this test. Another problem is a low contrast of a white animal on the whitened water surface, interfering with automated animal tracking. A unique installation based on EthoStudio has been designed at the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences and Institute of Automation and Electrometry, Siberian Branch, Russian Academy of Sciences. This tool automates the tracking of mice of any coat color under SPF conditions and comprises a plastic water tank (110 × 40 cm), a digital camera, and a light source. The water for the tank is sterilized using a Van Erp Blue Lagoon UV-C Tech 15000 ultraviolet decontaminator. The image of an animal is processed in a frame-by-frame manner using the EthoStudio software; the following parameters are calculated: escape latency, path length, cumulative distance to the platform, and the time spent in the sectors of tank. This installation has allowed us to study the spatial learning and memory in C57BL/6 and C57BL/6/Kaiso mice; in the latter strain, the gene encoding the methyl-DNA binding Kaiso protein is knocked out. It has been shown that the mice of these strains are capable of learning to find the platform in the Morris water maze and remember the location of the platform for at least the next four days.

Physiological Targets for the Treatment of Diabetic Encephalopathy

Diabetes mellitus is a chronic degenerative disease responsible for hyperglycemic episodes through insulin secretion deficiency or cellular resistance. Clinical diagnosis in diabetic patients established that this disease affects the CNS, damaging the brain and impairing cognition, and thus establishing a clinical diabetic condition named diabetic encephalopathy. Despite the physiological mechanisms responsible for the development diabetic encephalopathy are still unclear, an excessive formation of reactive oxygen species, an alteration of acetylcholinesterase activity, and a reduction of growth factor levels, may be related with the pathogenesis of this condition. Pharmacological treatments with natural compounds have been proven useful to treat and cure a wide variety of diseases through their antioxidant actions. This study built a compendium of chemical compounds used for the treatment of diabetic encephalopathy demonstrating the most important physiological targets that future drugs should aim for, reviewing them. As previously suspected, antioxidants and acetylcholinesterase inhibitors were useful to prevent memory loss in streptozotocin-induced animals. In addition, growth factors showed an improvement of memory in diabetic rodents. Most studies focused on antioxidant compounds despite cross studies researched both antioxidants and acetylcholinesterase activities. Therefore, it could be suggested that future studies regarding treatments for diabetic encephalopathy should focus on the antioxidant profile and acetylcholinesterase, since they seem to play pivotal roles in cognitive impairment in diabetes. No less important, studies with growth factors are also important physiological targets for treating the diabetic encephalopathy.

Y-미로에서 작업기억을 평가하는 새로운 방법 개발

The Y-maze is widely used to test working memory in behavioral science. For this purpose, spontaneous alternation behavior is monitored, and an increased percentage of spontaneous alternation is regarded as enhanced working memory. However, in some cases, the percentage of spontaneous alternation does not accurately reflect the extent of working memory in rodents. To complement the shortcomings of this measure, we developed a new method to evaluate working memory on the Y-maze. This is done by defining all spontaneous alternation cases and P i , the probability that the rodent achieved spontaneous alternation from each alternation case. After all P i -values acquired in each animal are summarized, the result is considered as entropy. To validate the new analytical method, mice were raised under either control or an enriched environmental condition for 10 weeks, and working memory behavior on the Y-maze was monitored. The results showed that the new analytical method successfully reproduced significance. In addition, the new method turned out to be more accurate than measurement of the percentage of spontaneous alternation, meaning that, to get higher entropy, alternation should be recorded in all arms and directions. Together, these data indicate that the new analytical method is a useful supplement to the method that compares the percentage of spontaneous alternation, and thus is a good tool with which to evaluate working memory in rodents.

Hippocampal-dependent memory in the plus-maze discriminative avoidance task: The role of spatial cues and CA1 activity

The plus-maze discriminative avoidance task (PMDAT) has been used to investigate interactions between aversive memory and an anxiety-like response in rodents. Suitable performance in this task depends on the activity of the basolateral amygdala, similar to other aversive-based memory tasks. However, the role of spatial cues and hippocampal-dependent learning in the performance of PMDAT remains unknown. Here, we investigated the role of proximal and distal cues in the retrieval of this task. Animals tested under misplaced proximal cues had diminished performance, and animals tested under both misplaced proximal cues and absent distal cues could not discriminate the aversive arm. We also assessed the role of the dorsal hippocampus (CA1) in this aversive memory task. Temporary bilateral inactivation of dorsal CA1 was conducted with muscimol (0.05μg, 0.1μg, and 0.2μg) prior to the training session. While the acquisition of the task was not altered, muscimol impaired the performance in the test session and reduced the anxiety-like response in the training session. We also performed a spreading analysis of a fluorophore-conjugated muscimol to confirm selective inhibition of CA1. In conclusion, both distal and proximal cues are required to retrieve the task, with the latter being more relevant to spatial orientation. Dorsal CA1 activity is also required for aversive memory formation in this task, and interfered with the anxiety-like response as well. Importantly, both effects were detected by different parameters in the same paradigm, endorsing the previous findings of independent assessment of aversive memory and anxiety-like behavior in the PMDAT. Taken together, these findings suggest that the PMDAT probably requires an integration of multiple systems for memory formation, resembling an episodic-like memory rather than a pure conditioning behavior. Furthermore, the concomitant and independent assessment of emotionality and memory in rodents is relevant to elucidate how these memory systems interact during aversive memory formation. Thus, the PMDAT can be useful for studying hippocampal-dependent memory when it involves emotional content.