Variations in the behaviors to novel objects among five inbred strains of mice

Novelty stimuli cause various behavioral responses, such as exploration and avoidance, and contextual variables may contribute to the behavioral outputs. Here, we tried to compare the behavioral responses to novel objects of five inbred strains of mice (C57BL/6J, 129/svJae, C3H/HeJ, BALB/cJ and DBA/2J) by using a modified novel object test where a small light-weight cube wrapped with paper was presented to mice in a home cage without beddings. In response to these objects, the C57BL/6J, 129/svJae and C3H/HeJ mice showed mild exploratory behaviors, such as approaching, sniffing or brief contact. In striking contrast, the BALB/cJ and DBA/2J mice, which have been known to show high avoidance/low exploration in other behavioral paradigms, exhibited play-like secondary reactions toward the objects after initial primary exploratory behaviors. Specifically, DBA/2J mice would move the object around in the cage, holding it with their mouths, and BALB/cJ mice would gnaw the object, eventually stripping off the wrapping paper. Such behaviors decreased when similar objects were presented repeatedly. The present results suggest that active manipulations of novel objects may be a relevant parameter for measuring novelty-induced behaviors in mice and appear to be strongly influenced by genetic factors.     

The Neural Basis of Object-Context Relationships on Aesthetic Judgment

The relationship between contextual information and object perception has received considerable attention in neuroimaging studies. In the work reported here, we used functional magnetic resonance imaging (fMRI) to investigate the relationship between aesthetic judgment and images of objects in their normal contextual setting versus images of objects in abnormal contextual settings and the underlying brain activity. When object-context relationships are violated changes in visual perception and aesthetic judgment emerges that exposes the contribution of vision to interpretations shaped by previous experience. We found that effects of context on aesthetic judgment modulates different memory sub-systems, while aesthetic judgment regardless of context recruit medial and lateral aspects of the orbitofrontal cortex, consistent with previous findings. Visual cortical areas traditionally associated with the processing of visual features are recruited in normal contexts, irrespective of aesthetic ratings, while prefrontal areas are significantly more engaged when objects are viewed in unaccustomed settings.     

Novel object exploration in ravens (Corvus corax): effects of social relationships

Social context has been shown to encourage, or to delay object exploration and learning. This ambiguity might be due to factors such as social relationships and personality of the individuals involved. Here, we investigated in ravens (Corvus corax) individuals' consistency in response to novel objects over development and across contexts: alone versus social. In the social setting we focussed on the effects of social relationships on social facilitation during the approach to novel objects. We tested 11 hand-raised ravens with novel objects individually at three and six months of age and in dyadic combinations at six months of age. Individuals were consistent over development and contexts in their response to different novel objects. Birds joined siblings faster to approach novel objects than non-siblings. They also spent more time sitting close to siblings than to non-siblings. In male-male dyads but not in female-female dyads, subordinates approached the novel objects significantly faster than dominant birds. In contrast, dominant males were the first to approach the novel objects in mixed-sex combinations. Hence, the effect of social context seems to depend on the social relationships towards the companions and on the combination of the sexes.     

Recognition memory in tree shrew (Tupaia belangeri) after repeated familiarization sessions

Recognition memories are formed during perceptual experience and allow subsequent recognition of previously encountered objects as well as their distinction from novel objects. As a consequence, novel objects are generally explored longer than familiar objects by many species. This novelty preference has been documented in rodents using the novel object recognition (NOR) test, as well is in primates including humans using preferential looking time paradigms. Here, we examine novelty preference using the NOR task in tree shrew, a small animal species that is considered to be an intermediary between rodents and primates. Our paradigm consisted of three phases: arena familiarization, object familiarization sessions with two identical objects in the arena and finally a test session following a 24-h retention period with a familiar and a novel object in the arena. We employed two different object familiarization durations: one and three sessions on consecutive days. After three object familiarization sessions, tree shrews exhibited robust preference for novel objects on the test day. This was accompanied by significant reduction in familiar object exploration time, occurring largely between the first and second day of object familiarization. By contrast, tree shrews did not show a significant preference for the novel object after a one-session object familiarization. Nonetheless, they spent significantly less time exploring the familiar object on the test day compared to the object familiarization day, indicating that they did maintain a memory trace for the familiar object. Our study revealed different time courses for familiar object habituation and emergence of novelty preference, suggesting that novelty preference is dependent on well-consolidated memory of the competing familiar object. Taken together, our results demonstrate robust novelty preference of tree shrews, in general similarity to previous findings in rodents and primates.     

The neurosteroid allopregnanolone impairs object memory and contextual fear memory in male C57BL/6J mice

Allopregnanolone (ALLO, or 3α-hydroxy-5α-pregnan-20-one) is a steroid metabolite of progesterone and a potent endogenous positive allosteric modulator of GABA-A receptors. Systemic ALLO has been reported to impair spatial, but not nonspatial learning in the Morris water maze (MWM) and contextual memory in rodents. These cognitive effects suggest an influence of ALLO on hippocampal-dependent memory, although the specific nature of the neurosteroid's effects on learning, memory or performance is unclear. The present studies aimed to determine: (i) the memory process(es) affected by systemic ALLO using a nonspatial object memory task; and (ii) whether ALLO affects object memory via an influence within the dorsal hippocampus. Male C57BL/6J mice received systemic ALLO either before or immediately after the sample session of a novel object recognition (NOR) task. Results demonstrated that systemic ALLO impaired the encoding and consolidation of object memory. A subsequent study revealed that bilateral microinfusion of ALLO into the CA1 region of dorsal hippocampus immediately following the NOR sample session also impaired object memory consolidation. In light of debate over the hippocampal-dependence of object recognition memory, we also tested systemic ALLO-treated mice on a contextual and cued fear-conditioning task. Systemic ALLO impaired the encoding of contextual memory when administered prior to the context pre-exposure session. Together, these results indicate that ALLO exhibits primary effects on memory encoding and consolidation, and extend previous findings by demonstrating a sensitivity of nonspatial memory to ALLO, likely by disrupting dorsal hippocampal function.     

Altered expression of synaptotagmin 13 mRNA in adult mouse brain after contextual fear conditioning

Contextual fear memory processing requires coordinated changes in neuronal activity and molecular networks within brain. A large number of fear memory-related genes, however, still remain to be identified. Synaptotagmin 13 (Syt13), an atypical member of synaptotagmin family, is highly expressed in brain, but its functional roles within brain have not yet been clarified. Here, we report that the expression of Syt13 mRNA in adult mouse brain was altered following contextual fear conditioning. C57BL/6 mice were exposed to a novel context and stimulated by strong electrical footshock according to a contextual fear conditioning protocol. After 24h, the mice were re-exposed to the context without electrical footshock for the retrieval of contextual fear memory. To investigate the relationship between Syt13 and contextual fear memory, we carried out in situ hybridization and analyzed gene expression patterns for Syt13 at four groups representing temporal changes in brain activity during contextual fear memory formation. Contextual fear conditioning test induced significant changes in mRNA levels for Syt13 within various brain regions, including lateral amygdala, somatosensory cortex, piriform cortex, habenula, thalamus, and hypothalamus, during both acquisition and retrieval sessions. Our data suggest that Syt13 may be involved in the process of contextual fear memory.     

A reduction in hippocampal GABAA receptor α5 subunits disrupts the memory for location of objects in mice

The memory for location of objects, which binds information about objects to discrete positions or spatial contexts of occurrence, is a form of episodic memory particularly sensitive to hippocampal damage. Its early decline is symptomatic for elderly dementia. Substances that selectively reduce α5‐GABA_A receptor function are currently developed as potential cognition enhancers for Alzheimer's syndrome and other dementia, consistent with genetic studies implicating these receptors that are highly expressed in hippocampus in learning performance. Here we explored the consequences of reduced GABA_Aα5‐subunit contents, as occurring in α5(H105R) knock‐in mice, on the memory for location of objects. This required the behavioral characterization of α5(H105R) and wild‐type animals in various tasks examining learning and memory retrieval strategies for objects, locations, contexts and their combinations. In mutants, decreased amounts of α5‐subunits and retained long‐term potentiation in hippocampus were confirmed. They exhibited hyperactivity with conserved circadian rhythm in familiar actimeters, and normal exploration and emotional reactivity in novel places, allocentric spatial guidance, and motor pattern learning acquisition, inhibition and flexibility in T‐ and eight‐arm mazes. Processing of object, position and context memories and object‐guided response learning were spared. Genotype difference in object‐in‐place memory retrieval and in encoding and response learning strategies for object–location combinations manifested as a bias favoring object‐based recognition and guidance strategies over spatial processing of objects in the mutants. These findings identify in α5(H105R) mice a behavioral–cognitive phenotype affecting basal locomotion and the memory for location of objects indicative of hippocampal dysfunction resulting from moderately decreased α5‐subunit contents.     

Blocking mineralocorticoid receptors prior to retrieval reduces contextual fear memory in mice

Background

Corticosteroid hormones regulate appraisal and consolidation of information via mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) respectively. How activation of these receptors modulates retrieval of fearful information and the subsequent expression of fear is largely unknown. We tested here whether blockade of MRs or GRs during retrieval also affects subsequent expression of fear memory.

Methodology/Principal Findings

Mice were trained in contextual or tone cue fear conditioning paradigms, by pairing mild foot shocks with a particular context or tone respectively. Twenty-four hours after training, context-conditioned animals were re-exposed to the context for 3 or 30 minutes (day 2); tone-conditioned animals were placed in a different context and re-exposed to one or six tones. Twenty-four hours (day 3) and one month later, freezing behavior to the aversive context/tone was scored again. MR or GR blockade was achieved by giving spironolactone or RU486 subcutaneously one hour before retrieval on day 2. Spironolactone administered prior to brief context re-exposure reduced freezing behavior during retrieval and 24 hours later, but not one month later. Administration of spironolactone without retrieval of the context or immediately after retrieval on day 2 did not reduce freezing on day 3. Re-exposure to the context for 30 minutes on day 2 significantly reduced freezing on day 3 and one month later, but freezing was not further reduced by spironolactone. Administration of spironolactone prior to tone-cue re-exposure on day 2 did not affect freezing behavior. Treatment with RU486 prior to re-exposure did not affect context or tone-cue fear memories at any time point.

Conclusions/Significance

We conclude that MR blockade prior to retrieval strongly reduces the expression of contextual fear, implying that MRs, rather than GRs, play an important role in retrieval of emotional information and subsequent fear expression.     

Comparison of preferences for object properties in the rat using paired- and free-choice paradigms

A common method for testing preference for objects is to determine which of a pair of objects is approached first in a paired-choice paradigm. In comparison, many studies of preference for environmental enrichment (EE) devices have used paradigms in which total time spent with each of a pair of objects is used to determine preference. While each of these paradigms gives a specific measure of the preference for one object in comparison to another, neither method allows comparisons between multiple objects simultaneously. Since it is possible that several EE objects would be placed in a cage together to improve animal welfare, it is important to determine measures for rats’ preferences in conditions that mimic this potential home cage environment. While it would be predicted that each type of measure would produce similar rankings of objects, this has never been tested empirically. In this study, we compared two paradigms: EE objects were either presented in pairs (paired-choice comparison) or four objects were presented simultaneously (simultaneous presentation comparison). We used frequency of first interaction and time spent with each object to rank the objects in the paired-choice experiment, and time spent with each object to rank the objects in the simultaneous presentation experiment. We also considered the behaviours elicited by the objects to determine if these might be contributing to object preference. We demonstrated that object ranking based on time spent with objects from the paired-choice experiment predicted object ranking in the simultaneous presentation experiment. Additionally, we confirmed that behaviours elicited were an important determinant of time spent with an object. This provides convergent evidence that both paired choice and simultaneous comparisons provide valid measures of preference for EE objects in rats.     

Spaced initial stimulus familiarization enhances novelty preference in Long-Evans rats

Berlyne [Berlyne, D.E., 1950. Novelty and curiosity as determinants of exploratory behaviour. Brit. J. Psychol. 41, 68–80] first illustrated that rats prefer to explore novel objects over ones with which they have had previous experience. Recently, variants on this novel object recognition (NOR) task have become widely popular and have been employed in numerous neuroscience and behavioral pharmacological studies investigating memory processes. Given this popularity, a thorough understanding of the various behavioral processes involved in novelty reaction and preference is essential. The current study compared the effects of spaced and massed initial stimulus exposures upon later object exploration and novel stimulus preference in Long-Evans rats. Results illustrated that a distributed initial stimulus familiarization procedure promoted greater novel object preference than did a massed procedure, and suggest that the novel object recognition task is sensitive to spacing effects in a similar fashion to more traditional learning paradigms. The mechanisms underlying such spacing effects are briefly discussed.     

Cortical analysis of visual context

Objects in our environment tend to be grouped in typical contexts. How does the human brain analyze such associations between visual objects and their specific context? We addressed this question in four functional neuroimaging experiments and revealed the cortical mechanisms that are uniquely activated when people recognize highly contextual objects (e.g., a traffic light). Our findings indicate that a region in the parahippocampal cortex and a region in the retrosplenial cortex together comprise a system that mediates both spatial and nonspatial contextual processing. Interestingly, each of these regions has been identified in the past with two functions: the processing of spatial information and episodic memory. Attributing contextual analysis to these two areas, instead, provides a framework for bridging between previous reports.     

The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts

Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1) monetary gain or loss based directly on performance, 2) monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3) success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences.     

Genetic and environmental influences on one-trial conditioned context aversion in mice

Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness-inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre-exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl-induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.     

Effects of suppressing gonadal hormones on response to novel objects in adolescent rats

Human adolescents exhibit higher levels of novelty-seeking behaviour than younger or older individuals, and novelty-seeking is higher in males than females from adolescence onwards. Gonadal hormones, such as testosterone and estradiol, have been suggested to underlie age and sex difference in response to novelty; however, empirical evidence in support of this hypothesis is limited. Here, we investigated whether suppressing gonadal hormone levels during adolescence affects response to novelty in laboratory rats. Previously, we have shown that male adolescent Lister-hooded rats (postnatal day, pnd, 40) exhibit a stronger preference than same-aged females for a novel object compared to a familiar object. In the current study, 24 male and 24 female Lister-hooded rats were administered with Antide (a gonadotrophin-releasing hormone antagonist), or with a control vehicle solution, at pnd 28. Antide provided long-term suppression of gonadal hormone production, as confirmed by ELISA assays and measurement of internal organs. Response to novel objects was tested at pnd 40 in Antide-treated and control subjects using a ‘novel object recognition’ task with a short (2-minute) inter-trial interval. In support of previous findings, control males exhibited a stronger preference than control females for novelty when presented with a choice of objects. Antide-treated males exhibited a significantly lower preference for novel objects compared to control males, whilst Antide-treated females did not differ significantly from control females in their preference for novelty. Antide treatment did not affect total time spent interacting with objects. We discuss how gonadal hormones might influence sex differences in preference for novelty during adolescence.     

昆明小鼠物体识别模型的建立及其在检测化学药物对记忆损伤中的应用

本研究的主要目的是建立昆明小鼠物体识别模型并评价该模型在安全药理学研究中的潜在应用价值。研究了昆明小鼠物体识别记忆随时间而减弱的特性,在训练结束后4h或1h,检测昆明小鼠的物体识别记忆,并评价了东莨胆碱对昆明小鼠物体识别记忆的影响。结果表明:1h间隔组昆明小鼠熟悉期探究物体的时间差和测试期探究物体的时间差存在显著差异(P<0.05),昆明小鼠在训练结束后1h记忆保持良好,可以进行物体识别;东莨胆碱组昆明小鼠熟悉期探究物体的时间差和测试期探究物体的时间差比较(P>0.05),没有显著性差异。因此,东莨胆碱损伤了昆明小鼠的物体识别记忆。用昆明小鼠建立的物体识别模型具有简单、快速、可靠等特点,在安全药理学研究中可用于检测化学药物对记忆的损伤。     

Effects of suppressing gonadal hormones on response to novel objects in adolescent rats

Human adolescents exhibit higher levels of novelty-seeking behaviour than younger or older individuals, and novelty-seeking is higher in males than females from adolescence onwards. Gonadal hormones, such as testosterone and estradiol, have been suggested to underlie age and sex difference in response to novelty; however, empirical evidence in support of this hypothesis is limited. Here, we investigated whether suppressing gonadal hormone levels during adolescence affects response to novelty in laboratory rats. Previously, we have shown that male adolescent Lister-hooded rats (postnatal day, pnd, 40) exhibit a stronger preference than same-aged females for a novel object compared to a familiar object. In the current study, 24 male and 24 female Lister-hooded rats were administered with Antide (a gonadotrophin-releasing hormone antagonist), or with a control vehicle solution, at pnd 28. Antide provided long-term suppression of gonadal hormone production, as confirmed by ELISA assays and measurement of internal organs. Response to novel objects was tested at pnd 40 in Antide-treated and control subjects using a ‘novel object recognition’ task with a short (2-minute) inter-trial interval. In support of previous findings, control males exhibited a stronger preference than control females for novelty when presented with a choice of objects. Antide-treated males exhibited a significantly lower preference for novel objects compared to control males, whilst Antide-treated females did not differ significantly from control females in their preference for novelty. Antide treatment did not affect total time spent interacting with objects. We discuss how gonadal hormones might influence sex differences in preference for novelty during adolescence.     

A single-rate context-dependent learning process underlies rapid adaptation to familiar object dynamics

Motor learning has been extensively studied using dynamic (force-field) perturbations. These induce movement errors that result in adaptive changes to the motor commands. Several state-space models have been developed to explain how trial-by-trial errors drive the progressive adaptation observed in such studies. These models have been applied to adaptation involving novel dynamics, which typically occurs over tens to hundreds of trials, and which appears to be mediated by a dual-rate adaptation process. In contrast, when manipulating objects with familiar dynamics, subjects adapt rapidly within a few trials. Here, we apply state-space models to familiar dynamics, asking whether adaptation is mediated by a single-rate or dual-rate process. Previously, we reported a task in which subjects rotate an object with known dynamics. By presenting the object at different visual orientations, adaptation was shown to be context-specific, with limited generalization to novel orientations. Here we show that a multiple-context state-space model, with a generalization function tuned to visual object orientation, can reproduce the time-course of adaptation and de-adaptation as well as the observed context-dependent behavior. In contrast to the dual-rate process associated with novel dynamics, we show that a single-rate process mediates adaptation to familiar object dynamics. The model predicts that during exposure to the object across multiple orientations, there will be a degree of independence for adaptation and de-adaptation within each context, and that the states associated with all contexts will slowly de-adapt during exposure in one particular context. We confirm these predictions in two new experiments. Results of the current study thus highlight similarities and differences in the processes engaged during exposure to novel versus familiar dynamics. In both cases, adaptation is mediated by multiple context-specific representations. In the case of familiar object dynamics, however, the representations can be engaged based on visual context, and are updated by a single-rate process.     

Aging,Culture, and Memory for Socially Meaningful Item-Context Associations: An East-West Cross-Cultural Comparison Study

Research suggests that people in Eastern interdependent cultures process information more holistically and attend more to contextual information than do people in Western independent cultures. The current study examined the effects of culture and age on memory for socially meaningful item-context associations in 71 Canadians of Western European descent (35 young and 36 older) and 72 native Chinese citizens (36 young and 36 older). All participants completed two blocks of context memory tasks. During encoding, participants rated pictures of familiar objects. In one block, objects were rated either for their meaningfulness in the independent living context or their typicality in daily life. In the other block, objects were rated for their meaningfulness in the context of fostering relationships with others or for their typicality in daily life. The encoding in each block was followed by a recognition test in which participants identified pictures and their associated contexts. The results showed that Chinese outperformed Canadians in context memory, though both culture groups showed similar age-related deficits in item and context memory. The results suggest that Chinese are at an advantage in memory for socially meaningful item-context associations, an advantage that continues from young adulthood into old age.     

Progesterone can enhance consolidation and/or performance in spatial, object and working memory tasks in Long-Evans rats

Progesterone has a ubiquitous role in reproduction and fitness and may influence cognitive performance. We examined the effects of administration of progesterone (a regimen that facilitates sexual behaviour) on consolidation of complex information in Long-Evans rats, Rattus norvegicus, that may be relevant for social engagement. We also examined the effects of subcutaneous progesterone administration (4 mg/kg versus oil vehicle placebo) on memory of ovariectomized rats during various cognitive tasks. Ovariectomized rats that received progesterone, versus the vehicle, immediately post-training were better able to find a hidden platform in the water maze. In a recognition task, rats that received progesterone spent more time in the novel arm of the Y-maze task than rats that received the vehicle. Ovariectomized rats that received progesterone immediately after training spent significantly more time exploring a novel object (compared to a familiar object) than did vehicle-administered rats. When socially relevant stimuli (i.e. objects with the scent of familiar or novel conspecifics) were used in the social cognition task, ovariectomized rats that received progesterone spent more time exploring the object with the novel conspecifics' scent than did vehicle-administered rats. Pairing of progesterone, but not the vehicle, conditioned a place preference to the originally nonpreferred side of the conditioning chamber. We found no significant differences in motor activity measures in these tasks due to progesterone treatment. These results suggest that progesterone's effects to improve cognitive processes with nonsocial and socially relevant stimuli, as well as have reinforcing effects, may underlie some of its salient effects on reproduction-related behaviours.