Preference For Novel Object Research Articles

Comprehensive behavioral analysis of RNG105 (Caprin1) heterozygous mice: Reduced social interaction and attenuated response to novelty.

RNG105 (also known as Caprin1) is a major RNA-binding protein in neuronal RNA granules, and is responsible for mRNA transport to dendrites and neuronal network formation. A recent study reported that a heterozygous mutation in the Rng105 gene was found in an autism spectrum disorder (ASD) patient, but it remains unclear whether there is a causal relation between RNG105 deficiency and ASD. Here, we subjected Rng105+/− mice to a comprehensive behavioral test battery, and revealed the influence of RNG105 deficiency on mouse behavior. Rng105+/− mice exhibited a reduced sociality in a home cage and a weak preference for social novelty. Consistently, the Rng105+/− mice also showed a weak preference for novel objects and novel place patterns. Furthermore, although the Rng105+/− mice exhibited normal memory acquisition, they tended to have relative difficulty in reversal learning in the spatial reference tasks. These findings suggest that the RNG105 heterozygous knockout leads to a reduction in sociality, response to novelty and flexibility in learning, which are implicated in ASD-like behavior.

Object recognition memory in zebrafish

The novel object recognition, or novel-object preference (NOP) test is employed to assess recognition memory in a variety of organisms. The subject is exposed to two identical objects, then after a delay, it is placed back in the original environment containing one of the original objects and a novel object. If the subject spends more time exploring one object, this can be interpreted as memory retention. To date, this test has not been fully explored in zebrafish (Danio rerio). Zebrafish possess recognition memory for simple 2- and 3-dimensional geometrical shapes, yet it is unknown if this translates to complex 3-dimensional objects. In this study we evaluated recognition memory in zebrafish using complex objects of different sizes. Contrary to rodents, zebrafish preferentially explored familiar over novel objects. Familiarity preference disappeared after delays of 5mins. Leopard danios, another strain of D. rerio, also preferred the familiar object after a 1min delay. Object preference could be re-established in zebra danios by administration of nicotine tartrate salt (50mg/L) prior to stimuli presentation, suggesting a memory-enhancing effect of nicotine. Additionally, exploration biases were present only when the objects were of intermediate size (2×5cm). Our results demonstrate zebra and leopard danios have recognition memory, and that low nicotine doses can improve this memory type in zebra danios. However, exploration biases, from which memory is inferred, depend on object size. These findings suggest zebrafish ecology might influence object preference, as zebrafish neophobia could reflect natural anti-predatory behaviour.

Centrally-administered oxytocin promotes preference for familiar objects at a short delay in ovariectomized female rats

Oxytocin has been previously associated with social attachment behaviors in various species, however, most studies focused on partner preference in the socially-monogamous prairie vole. In these, oxytocin treatment was shown to promote partner preference, such that females receiving either central or pulsatile peripheral administration would spend more time with a familiar male. This behavioral outcome was blocked by oxytocin receptor antagonist treatment. The aim of the current study was to further explore the preference-inducing properties of oxytocin by examining its effects on object preference on ovariectomized female rats. In other words, we assessed whether these effects would apply to objects and if they would be persistent across species. Eight rats were infused with oxytocin into the left ventricle and object preference was assessed at two delays: 30min and 4h. At the 30min delay, oxytocin-treated animals showed preference for the familiar object, whereas saline-treated controls exhibited preference for the novel object. At the 4h delay, both groups showed novel-object preference. Our findings show that oxytocin modulates object preference in the female rat at a shorter delay, similar to the findings from partner-preference studies in the prairie vole, suggesting that the mechanisms driving object preference might be in part similar to those responsible for partner preference.

Chronic transcranial focal stimulation from tripolar concentric ring electrodes does not disrupt memory formation in rats.

Non-invasive electrical brain stimulation has shown potential utility as a treatment for seizures in epilepsy patients. Transcranial focal stimulation (TFS) via tripolar concentric ring electrodes (TCREs) has been effective in reducing seizure severity in acute rodent models, but it has yet to be determined whether or not it will serve as a viable long-term treatment strategy. Prior experiments indicate that a single dose of TFS via TCRE does not impact short- or long-term memory formation. The present study investigated if five daily doses of TFS via a TCRE on the scalp affected the memory. The spontaneous object recognition (SOR) test was used to evaluate the memory. Sham and TFS-treated groups were evaluated and both showed comparable levels of preference for novel objects, indicating successful memory formation. More work on repeated dosage strategies is important for establishing the safety and efficacy of TFS as a putative treatment.

Systemic and intra-rhinal-cortical 17-β estradiol administration modulate object-recognition memory in ovariectomized female rats

Previous studies using the novel-object-preference (NOP) test suggest that estrogen (E) replacement in ovariectomized rodents can lead to enhanced novelty preference. The present study aimed to determine: 1) whether the effect of E on NOP performance is the result of enhanced preference for novelty, per se, or facilitated object-recognition memory, and 2) whether E affects NOP performance through actions it has within the perirhinal cortex/entorhinal cortex region (PRh/EC). Ovariectomized rats received either systemic chronic low 17-β estradiol (E2; ~20pg/ml serum) replacement alone or in combination with systemic acute high administration of estradiol benzoate (EB; 10μg), or in combination with intracranial infusions of E2 (244.8pg/μl) or vehicle into the PRh/EC. For one of the intracranial experiments, E2 was infused either immediately before, immediately after, or 2h following the familiarization (i.e., learning) phase of the NOP test. In light of recent evidence that raises questions about the internal validity of the NOP test as a method of indexing object-recognition memory, we also tested rats on a delayed nonmatch-to-sample (DNMS) task of object recognition following systemic and intra-PRh/EC infusions of E2. Both systemic acute and intra-PRh/EC infusions of E enhanced novelty preference, but only when administered either before or immediately following familiarization. In contrast, high E (both systemic acute and intra-PRh/EC) impaired performance on the DNMS task. The findings suggest that while E2 in the PRh/EC can enhance novelty preference, this effect is probably not due to an improvement in object-recognition abilities.

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.

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.

Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris)

Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study, we first established the applicability of the visual paired comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved.

Object familiarization and novel-object preference in rats

We investigated whether object familiarization was related to novel-object preference in the novel-object preference (NOP) test in rats. In Experiment 1, we found that no significant correlation existed between the time spent investigating 2 identical copies of a sample object and the degree of preference for a novel object. In Experiment 2, rats investigated 2 identical sample objects for a total of 5, 30, 60, 90 or 120s. Investigatory preference for the novel object was compared to chance expectancy as well as between the groups. Only the 90-s group and the 120-s group displayed above-chance investigatory preference for the novel object, but novel-object preference for these 2 groups did not differ from each other, suggesting that a minimal amount of sample object investigation is necessary for rats to develop a novel-object preference, beyond which no increase in novel-object preference was found. In Experiments 3 and 4, normal rats and rats with hippocampal lesions were given repeated test trials, with the same sample object presented with a different novel object, at 24-h and (Experiment 3) and 35-s intervals (Experiment 4). In both experiments, novel-object preference did not increase in magnitude with repeated sample object exposures, suggesting that increased familiarity with the sample object does not result in increased novel-object preference. Rats with lesions of the dorsal hippocampus showed an unreliable investigatory preference for the novel object. These results are discussed in terms of the potential limitations of the NOP test as a tool for the assessment of object-recognition memory in rats.

A limited role for the hippocampus in the modulation of novel-object preference by contextual cues

Recent evidence suggests that rats require an intact hippocampus in order to recognize familiar objects when they encounter them again in a different context. The two experiments reported here further examined how changes in context affect rats' performance on the novel-object preference (NOP) test of object-recognition memory, and how those effects interact with the effects of HPC damage. Rats with HPC lesions and control rats received NOP testing in either the same context in which they had previously encountered sample objects, or in a different but equally familiar context. In Experiment 1, the two contexts had very few overlapping cues within or outside the apparatus; thus, the differences between them were global. Consistent with previous results, control rats showed a novel-object preference in both the unchanged and (globally) changed contexts, whereas rats with HPC lesions displayed a preference only in the unchanged context. In Experiment 2, the context shift included only local features proximal to the test objects. The main results were the reverse of Experiment 1--rats with HPC lesions displayed a novel-object preference in both the unchanged and (locally) changed contexts, whereas control rats displayed a preference only in the unchanged context. The findings are consistent with the view that HPC damage does not cause a general inability to recognize objects, nor an inability to encode or store a representation of the context in which the objects are encountered. They suggest instead that HPC damage impairs the ability to remember specific locations of familiar objects within a particular context.

Neophilia in domestic dogs (Canis familiaris) and its implication for studies of dog cognition

This study examined novel-object preference in dogs. In a free choice test 17 dogs were presented with a novel toy in a line up with two familiar toys. The unfamiliar object was chosen first in 38 out 50 tests suggesting a strong preference for novel over familiar items. Neophilia may be an adaptive trait for domestic dogs that has helped their adaptation towards man.

D-Serine and a glycine transporter inhibitor improve MK-801-induced cognitive deficits in a novel object recognition test in rats

Compounds enhancing N-methyl-d-aspartate (NMDA) glutamate receptor function have been reported to improve cognitive deficits. Since cognitive deficits are considered to be the core symptom of schizophrenia, enhancing NMDA receptor function represents a promising approach to treating schizophrenia. In the present study, we investigated whether d-serine or a glycine transporter inhibitor N-[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl]sarcosine (NFPS), both of which enhance NMDA receptor function, could improve MK-801-induced cognitive deficits in rats, and compared their effects with those of the atypical antipsychotic clozapine and of the typical antipsychotic haloperidol. To assess cognitive function, we used a novel object recognition test in rats that measured spontaneous exploratory activity of a novel object when paired with a familiar object. We then evaluated the effects of the compounds on cognitive deficits induced by treatment with MK-801, the NMDA receptor antagonist. Pretreatment with clozapine (1, 5mg/kg, i.p.) but not haloperidol (0.03, 0.1mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits. Pretreatment with d-serine at 800mg/kg (i.p.) or NFPS (0.3, 1mg/kg, i.p.) significantly improved MK-801-induced cognitive deficits under this test paradigm. These findings suggest that impaired preference for novel objects induced by MK-801 in the novel object recognition test could be a useful animal model for evaluating the efficacy of compounds targeting the cognitive deficits observed in schizophrenic patients. The results also suggest that enhancing NMDA receptor function is an effective way for treating the cognitive deficits associated with schizophrenia.

Perirhinal cortex damage and anterograde object-recognition in rats after long retention intervals

Damage to the perirhinal cortex (PRh) in rats impairs anterograde object-recognition memory after retention intervals of up to several hours, but there is little direct evidence to link PRh function to object-recognition abilities after substantially longer intervals that span several days or weeks. We assessed the effects of PRh lesions on anterograde object recognition using a novel-object preference test, with retention intervals lasting 24 h and 3 weeks. The rats received multiple exposures to the sample object during the learning phase—5 min per day on 5 consecutive days. Control rats displayed a significant novel-object preference after both retention intervals, indicating recognition of the sample object, whereas the rats with PRh lesions displayed a significant preference after the 24-h interval, but not after the 3-week interval. When the learning phase of the trial was shortened to a single 5-min session, the PRh group was impaired in the 24-h condition. The findings indicate that the disruptive effects of PRh damage on anterograde object recognition persist over very long postlearning intervals. The results indicate further that object recognition impairments following PRh damage are not ubiquitous, and that learning conditions play a significant role in determining the subsequent recognition performance in rats with PRh damage.

Enhanced context-dependency of object recognition in rats with hippocampal lesions

Object recognition memory was assessed on a novel-object preference (NOP) task in rats with lesions of the hippocampal formation (HPC). The learning and test phases of NOP trials occurred in either the same context or in different contexts. When the learning and test contexts were the same, rats with HPC lesions performed like control rats, displaying a significant tendency to investigate a novel object more than a familiar sample object. When the test occurred in a context that was familiar but different from the learning context, performance was unaffected in control rats, but rats with HPC lesions no longer discriminated between the objects, and therefore showed no evidence of recognizing the sample object. When the test context was unfamiliar, novel-object preference in control rats was attenuated but still above chance levels, whereas rats with HPC lesions did not show a preference. The data suggest that the HPC is not critical for encoding or retrieving conjunctive representations of the context in which incidental learning occurs, whereas it plays an essential role in recognition of objects that are subsequently encountered in different contexts.

Hippocampal damage and anterograde object-recognition in rats after long retention intervals

Although several studies in rats have found that hippocampal damage has negligible effects on anterograde object-recognition memory, the findings are not entirely conclusive, because most studies have used retention intervals lasting only a few hours. We assessed the effects of neurotoxic hippocampal lesions on anterograde object recognition, using a novel-object preference test, with retention intervals that were considerably longer than in previous studies-24 h, 1 week, and 3 weeks. To promote object recognition after such long intervals, rats were familiarized with a sample object in an open field for 5 min/day for 5 consecutive days. Recognition was assessed by comparing the amount of time spent investigating the sample versus a novel object on a preference test at one of the postlearning intervals. The rats with hippocampal lesions displayed a normal novelty preference after a 3-week interval, and their performance across the three delay conditions was not significantly different from that of control rats. The findings indicate that extensive hippocampal damage spares anterograde object recognition in rats, even after retention intervals lasting days or weeks.

Retrograde and anterograde object recognition in rats with hippocampal lesions.

Retrograde and anterograde object-recognition memory was assessed in rats with cytotoxic lesions of the hippocampal formation (HPC), using a paradigm based on the natural tendency of rats to spend more time exploring novel objects than familiar objects. The rats were allowed to explore a sample object for 5 min/day on 5 consecutive days, either 5 weeks or 1 week before surgery. After surgery, retrograde recognition was assessed by comparing the amount of time spent exploring the sample versus a novel object in a free-choice situation. Control rats spent more time exploring the novel object than the sample objects from both presurgery time periods, whereas rats with HPC lesions did not discriminate between the novel objects and sample objects from either presurgery time period. Despite their deficits on the retrograde recognition test, the rats with HPC lesions performed like control rats on anterograde recognition tests, displaying a strong exploratory preference for novel objects over sample objects, with retention delays of either 15 min or 24 h. The findings suggest that extrahippocampal circuitry is capable of supporting object recognition, but only if the HPC does not participate in encoding the original encounter with the object.

The role of environmental familiarization in novel-object preference

The experiments in this report examined the behavioral variables modulating novel-object preference in a widely used ‘object recognition’ preparation. This preparation takes advantage of the tendency of rats to interact more with a novel than a familiar ‘sample’ object in a free-choice situation. Experiment 1 examined the interaction between environmental familiarization and the duration of sample-object exposure in the development of a novel-object preference. Interaction with the sample object during sample-object exposure was increased when rats were given time in the environment prior to presentation of the sample object. Also, provided that the sample-object exposure was greater than 2 min, rats given environmental familiarization time prior to sample-object exposure displayed a novel-object preference. Rats that received the same amount of sample-object exposure without prior exposure to the environment alone did not discriminate between the sample and novel object. In Experiments 2 and 3, sample-object exposure occurred in a different environment than the novel-object test. Novel-object preference was not affected regardless of whether that testing environment was familiar or novel. This result differs from previous work that finds that an object recovers some novelty when moved to a new spatial location.

Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition

The natural preference for novel objects which is displayed by rats has been used as a behavioural index to test object recognition. In this series of experiments the standard spontaneous recognition task was extended to look at other types of recognition memory; memory for place (recognition that an object is in a location where previously there had been no object), memory for object in place (recognition that a specific object has changed position with another object) and memory for context (recognition that a familiar object is in a context different to that in which it was previously encountered). We also included a standard test of object recognition in which successful discrimination relied primarily on visual cues. In addition, we looked at how the differential exploration of objects varied within the 3 min of the test phase. The results showed that rats were sensitive to the changes made in all of the test conditions and that the level of discrimination varied within the 3 min test phase. In the standard condition and the context condition, the first 2 min were found to be the most sensitive period. In the two conditions involving a position change, discrimination was only evident in the first minute.

Development of orienting to locations and objects in human infants.

Two experiments investigated preference for orienting to novel locations and novel objects in young infants. Adults and infants of six months and older show a propensity to orient to locations that have not recently been inspected (inhibition of return). Preference for novel locations undergoes development. We show that, similar to adults, its development is related to the ability to program eye movements to attended locations. This preference appears to emerge as infants gain the ability to program eye movements to target locations. Experiment 1 demonstrates that three-month-olds show inhibition of return for 10 degrees target eccentricities, but not for 30 degrees target eccentricities. In a second experiment, three- and six-month-old infants oriented to 10 degrees targets that varied in location and object identity. Infants of both ages strongly preferred orienting to novel objects at novel locations. At three months, the preference for novel objects was equal to the preference for novel locations, while at six months a tendency to prefer novel objects over novel locations emerged. Overall, the findings support separate development of these two forms of novelty preference, and suggest that novel location preferences (inhibition of return) relates closely to the eye movement system. The findings are discussed in relation to issues concerning development, physiology, and cognition.

The Maudsley rat strains as a probe to investigate noradrenergic-cholinergic interaction in cognitive function

Central noradrenergic function in relation to cognitive performance was studied in the Maudsley rat strains. Neurochemical studies revealed a higher response to acute stressin the locus coeruleus (LC) in the Maudsley reactives (MR) than in the Maudsley non-reactives (MNRA). Autoradiographic studies showed that MNRAs had greater 125I clonidine binding to α2 receptors in LC, which was accompanied by a higher behavioral sensitivity to clonidene. MRs had a deficit in working memory, but were superior to MNRAs in two reference memory tasks. MRs displayed a stronger preference for novel objects, with no strain differences in general exploratory activity. The behavioral profile of the MRs is similar to rats treated with drugs which enhance noradrenergic function. Furthermore, MNRA rats had greater availability of muscarinic receptors, which correlated with behavioral performance in the spatial working memory task. The differences in noradrenergic and cholinergic systems and their relationship to the behavioral profile make the Maudsley strains a useful tool to probe the interaction between the two neurotransmitter systems in cognitive function.