Correlations of recognition memory performance with expression and methylation of brain-derived neurotrophic factor in rats

Object recognition memory allows discrimination between novel and familiar objects. This kind of memory consists of two components: recollection, which depends on the hippocampus, and familiarity, which depends on the perirhinal cortex (Pcx). The importance of brain-derived neurotrophic factor (BDNF) for recognition memory has already been recognized. Recent evidence suggests that DNA methylation regulates the expression of BDNF and memory. Behavioral and molecular approaches were used to understand the potential contribution of DNA methylation to recognition memory. To that end, rats were tested for their ability to distinguish novel from familiar objects by using a spontaneous object recognition task. Furthermore, the level of DNA methylation was estimated after trials with a methyl-sensitive PCR. We found a significant correlation between performance on the novel object task and the expression of BDNF, negatively in hippocampal slices and positively in perirhinal cortical slices. By contrast, methylation of DNA in CpG island 1 in the promoter of exon 1 in BDNF only correlated in hippocampal slices, but not in the Pxc cortical slices from trained animals. These results suggest that DNA methylation may be involved in the regulation of the BDNF gene during recognition memory, at least in the hippocampus.     

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.     

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.     

Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory

We establish the importance of cholinergic neurotransmission to both recognition memory and plasticity within the perirhinal cortex of the temporal lobe. The muscarinic receptor antagonist scopolamine impaired the preferential exploration of novel over familiar objects, disrupted the normal reduced activation of perirhinal neurones to familiar compared to novel pictures, and blocked production of long-term depression (LTD) but not long-term potentiation (LTP) of synaptic transmission in perirhinal slices. The consistency of these effects across the behavioral, systems, and cellular levels of analysis provides strong evidence for the involvement of cholinergic mechanisms in synaptic plastic processes within perirhinal cortex that are necessary for recognition memory.     

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。     

Sleep Deprivation in the Dark Period Does Not Impair Memory in OF1 Mice

There is increasing evidence that sleep facilitates memory acquisition and consolidation. Moreover, the sleep-wake history preceding memory acquisition and retention as well as circadian timing may be important. We showed previously that sleep deprivation (SD) following learning in OF1 mice impaired their performance on an object recognition task. The learning task was scheduled at the end of the 12 h dark period and the test 24 h later. To investigate the influence of the prominent circadian sleep-wake distribution typical for rodents, we now scheduled the learning task at the beginning of the dark period. Wakefulness following immediately after the learning task was attained either by gentle interference (SD; n?=?20) or by spontaneous wheel running (RW; n?=?20). Two control groups were used: one had no RW throughout the experiment (n?=?23), while the other group's wheel was blocked immediately after acquisition (n?=?16), thereby preventing its use until testing. Recognition memory, defined as the difference in exploration of a novel and of familiar objects, was assessed 24 h later during the test phase. Motor activity and RW use were continuously recorded. Remarkably, performance on the object recognition task was not influenced by the protocols; the waking period following acquisition did not impair memory, independent of the method inducing wakefulness (i.e., sleep deprivation or spontaneous running). Thus, all groups explored the novel object significantly longer than the familiar ones during the test phase. Interestingly, neither the amount of rest lost during the SD interventions nor the amount of rest preceding acquisition influenced performance. However, the total amount of rest obtained by the control and SD mice subjected to acquisition at “dark offset” correlated positively (r?=?0.66) with memory at test, while no such relationship occurred in the corresponding groups tested at dark onset. Neither the amount of running nor intermediate rest correlated with performance at test in the RW group. We conclude that interfering with sleep during the dark period does not affect object recognition memory consolidation.     

Gonadectomy impairs T-maze acquisition in adult male rats

Recent studies have shown that chronic gonadectomy increases the density of dopaminergic axons in prefrontal but not sensorimotor cortices in adult male rats. Since supranormal prefrontal cortical dopamine stimulation is known to impair rats' performance in T-maze delayed alternation paradigms, we tested whether long-term gonadectomy might also impair T-maze performance. For comparison, sensorimotor functions were also assessed. Adult male rats were gonadectomized and placebo-, estradiol-, or testosterone propionate-treated or were sham operated and placebo-treated. Four weeks after surgery, the subjects were tested using a rotorod apparatus and in the acquisition of a T-maze delayed alternation paradigm. Gonadectomized placebo-treated and estradiol-treated rats took significantly longer to acquire the T-maze rule than controls, and gonadectomized, testosterone-treated rats acquired the task within the same time frame as controls. No group differences were detected in rotorod performance. Thus, chronic gonadectomy induced testosterone-sensitive, estradiol-insensitive acquisition deficits in a spatial learning task but had no demonstrable effects on the sensorimotor functions tested.     

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.     

Prenatal testosterone improves the spatial learning and memory by protein synthesis in different lobes of the brain in the male and female rat

The high density of the steroid hormone receptors in the structures of temporal lobe involved in learning and memory, such as the hippocampus, perirhinal cortex, entorhinal cortex and amigdaloid complex, shows that there must be a direct relationship between gonadal hormones and organizational effects of steroid hormones in those structures during development of the nervous system. The present study was undertaken in order to investigate the effect of testosterone administration during the third week of gestation on the spatial memory formation of the offspring rats and the level of soluble proteins in the temporal lobe and frontal lobe of brain, as evidence of important organizational effects of androgens during prenatal development in brain sexual dimorphism. Animals have received testosterone undecanoate on days 14, 15, 16 and 19, 20, 21 of gestation. Learning and memory tests were started 100 days after the testosterone treatment. At the end of the experiments, the temporal and frontal lobes of brain were removed for assessing the level of soluble proteins. Testosterone treatment significantly improved spontaneous alternations percentage of male offspring in Y-maze task comparative with female offspring and reference memory in radial 8 arm-maze task (decreasing in number of reference memory errors in both male and female offspring groups), suggesting effects of both short and long-term memory. Also, testosterone significantly increased the brain soluble protein level of treated female rats in 14–16 prenatal days compared with the control group as well as the brain soluble protein level of treated male rats. These results suggest that steroid hormones play an important role in the spatial learning and memory formation by means of protein synthesis in different lobes of the brain.     

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.     

Size-Sensitive Perceptual Representations Underlie Visual and Haptic Object Recognition

A variety of similarities between visual and haptic object recognition suggests that the two modalities may share common representations. However, it is unclear whether such common representations preserve low-level perceptual features or whether transfer between vision and haptics is mediated by high-level, abstract representations. Two experiments used a sequential shape-matching task to examine the effects of size changes on unimodal and crossmodal visual and haptic object recognition. Participants felt or saw 3D plastic models of familiar objects. The two objects presented on a trial were either the same size or different sizes and were the same shape or different but similar shapes. Participants were told to ignore size changes and to match on shape alone. In Experiment 1, size changes on same-shape trials impaired performance similarly for both visual-to-visual and haptic-to-haptic shape matching. In Experiment 2, size changes impaired performance on both visual-to-haptic and haptic-to-visual shape matching and there was no interaction between the cost of size changes and direction of transfer. Together the unimodal and crossmodal matching results suggest that the same, size-specific perceptual representations underlie both visual and haptic object recognition, and indicate that crossmodal memory for objects must be at least partly based on common perceptual representations.     

A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat

Background

We aimed to further understand the relationship between cAMP concentration and mnesic performance.

Methods and Findings

Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p.), rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p.) and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p.) before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices) before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold), prefrontal (1.3 fold) and perirhinal (1.3 fold) cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold) from drug-treated rats (except for milrinone+RS 67333 treatment). After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold) and the perirhinal cortex (2.1 fold) from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold) and milrinone (respectively 1.46 fold and 1.56 fold)-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h).

Conclusions

Our results strongly suggest that a “pre-sample” early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.     

Gonadal hormones modulate sex differences in judgments of relative numerousness in meadow voles, Microtus pennsylvanicus

Animals in a variety of taxa discriminate between a greater quantity and a lesser quantity of the same object, an ability that is referred to as relative numerousness judgment. For example, meadow voles can distinguish between areas containing more over-marks by one opposite-sex scent donor and fewer over-marks by another opposite-sex scent donor. Females appear to be able to make better discriminations between more or less over-marks than do males. In that gonadal hormones have been implicated in modulating cognitive function associated with spatial tasks, we tested the hypothesis that high titers of testosterone and estradiol are necessary for male and female voles, respectively, to distinguish between the top- and bottom-scent donors in an area containing mixed over-marks. We gonadectomized voles, giving them either gonadal hormone replacement (testosterone for males and estradiol for females) or no hormone replacement, and tested their spontaneous judgments of distinguishing between the top- and bottom-scent donors in an area containing mixed over-marks; a task involving judgments of relative numerousness. Female voles given replacement estradiol performed better than did female voles not given replacement estradiol in determining the top-scent and bottom-scent males in areas containing mixed over-marks. In contrast, males not treated with replacement testosterone performed better than did males treated with testosterone in determining the top-scent and bottom-scent males in areas containing mixed over-marks. Thus, high titers of estradiol and low titers of testosterone are associated with better performance on tasks involving relative numerousness in female and male voles, respectively. The results of this task on relative numerousness judgments are discussed in relation to the effects of gonadal steroid hormone on spatial ability, a closely related cognitive domain, and the social biology of meadow voles.     

Object/Context Specific Memory Deficits following Medial Frontal Cortex Damage in Mice

Recent evidence suggests that the medial prefrontal cortex (MFC) is important for processing contextual information. Here we evaluate the performance of mice with MFC damage in a discrimination task that requires an association between an object and the context in which it was experienced (the object/context mismatch task), as well as a version of the novel object preference task that does not require knowledge of contextual information to resolve. Adult C57/BL6 mice received aspiration lesions of the MFC or control surgery. Upon recovery, mice were tested in the object/context mismatch and novel object preference tasks. The object/context mismatch task involved exposing mice to two different contexts, each of which housed a unique pair of identical objects. After a brief delay, mice were re-exposed to one of the contexts, this time with one object that was congruent with that context and one that was not. Novel object preference was performed within a single context, housing an identical pair of objects. After the initial exposure and following a brief delay, mice were re-exposed to the context, this time housing a familiar and a novel object. Control mice were able to successfully resolve the object/context mismatch and novel object preference discriminations, investigating the incongruent/novel object within each task significantly greater than chance. Mice with MFC damage experienced deficits in the object/context mismatch task but not the novel object preference task. These findings add to a growing body of evidence that demonstrate a critical role for the MFC in contextual information processing.     

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.     

Neural Androgen Receptor Deletion Impairs the Temporal Processing of Objects and Hippocampal CA1-Dependent Mechanisms

We studied the role of testosterone, mediated by the androgen receptor (AR), in modulating temporal order memory for visual objects. For this purpose, we used male mice lacking AR specifically in the nervous system. Control and mutant males were gonadectomized at adulthood and supplemented with equivalent amounts of testosterone in order to normalize their hormonal levels. We found that neural AR deletion selectively impaired the processing of temporal information for visual objects, without affecting classical object recognition or anxiety-like behavior and circulating corticosterone levels, which remained similar to those in control males. Thus, mutant males were unable to discriminate between the most recently seen object and previously seen objects, whereas their control littermates showed more interest in exploring previously seen objects. Because the hippocampal CA1 area has been associated with temporal memory for visual objects, we investigated whether neural AR deletion altered the functionality of this region. Electrophysiological analysis showed that neural AR deletion affected basal glutamate synaptic transmission and decreased the magnitude of N-methyl-D-aspartate receptor (NMDAR) activation and high-frequency stimulation-induced long-term potentiation. The impairment of NMDAR function was not due to changes in protein levels of receptor. These results provide the first evidence for the modulation of temporal processing of information for visual objects by androgens, via AR activation, possibly through regulation of NMDAR signaling in the CA1 area in male mice.     

Single, brief exposure to a 50 Hz magnetic field does not affect the performance of an object recognition task in adult mice

A number of studies have shown that power frequency magnetic fields may affect spatial memory functions in rodents. An experiment was performed using a spontaneous object recognition task to investigate if nonspatial working memory was similarly affected. Memory changes in adult, male C57BL/6J mice were assessed by measuring the relative time within which the animals explored familiar or novel stimulus objects. Between initial testing and retesting, the animals were exposed for 45 min to a 50 Hz magnetic field at either 7.5 microT, 75 microT or 0.75 mT. Other animals were sham-exposed with ambient fields of less than 50 nT. No significant field-dependent effects on the performance of the task were observed at any flux density (for all measures, P > 0.05). These data provide no evidence to suggest that nonspatial working memory was affected in mice by acute exposure to an intense 50 Hz magnetic field.     

Chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment

We hypothesized that chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, to young adult male rats would prevent/ameliorate fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment. Eighty 12-14-week-old young adult male Fischer 344 rats received either: (1) sham irradiation, (2) 40 Gy of fractionated whole-brain irradiation delivered as two 5 Gy fractions/week for 4 weeks, (3) sham irradiation plus continuous administration of 15 mg/L of ramipril in the drinking water starting 3 days before irradiation, or (4) fractionated whole-brain irradiation plus ramipril. Cognitive function was assessed using a perirhinal cortex-dependent version of the novel object recognition task 26 weeks after irradiation. Microglial activation was determined in the perirhinal cortex and the dentate gyrus of the hippocampus 28 weeks after irradiation using the ED1 antibody. Neurogenesis was assessed in the granular cell layer and subgranular zones of the dentate gyrus using a doublecortin antibody. Fractionated whole-brain irradiation led to: (1) a significant impairment in perirhinal cortex-dependent cognitive function, (2) a significant increase in activated microglia in the dentate gyrus but not in the perirhinal cortex, and (3) a significant decrease in neurogenesis. Continuous administration of ramipril before, during, and after irradiation prevented the fractionated whole-brain irradiation-induced changes in perirhinal cortex-dependent cognitive function, as well as in microglial activation in the dentate gyrus. Thus, as hypothesized, continuous administration of the angiotensin-converting enzyme inhibitor, ramipril, can prevent the fractionated whole-brain irradiation-induced impairment in perirhinal cortex-dependent cognitive function.     

Object recognition as a measure of memory in 1–2?years old transgenic minipigs carrying the APPsw mutation for Alzheimer’s disease

Alzheimer??s disease (AD) is a disabling, fatal disease, where animal models potentially can enable investigation of aetiology and treatment. The first litter of G?ttingen minipigs carrying a mutation for human AD was born in 2007, showing transgene expression. In human AD patients, memory impairment is the most striking and consistent feature. The aim of the present study was to examine effects of the APPsw transgene on memory of AD minipigs compared with non-transgenic controls at two ages (1?C2?years) using the spontaneous object recognition test (SORT), which is based on behavioural discrimination of familiar and novel objects. No significant difference between AD minipigs and controls was found when comparing object recognition as a measure of memory. The minipigs did explore the novel object significantly more than the familiar, indicating the expected recognition of the familiar object. Two different inter-phase intervals were used (IPI: 10?C40?min). For both ages, object recognition was evident using 10?min IPI. When using 40?min IPI, object recognition was evident only at age 1?year. Comparing memory of a relatively small group of AD minipigs and controls at two rather young ages using the SORT, we were not able to show memory impairment in APPsw carrying minipigs. Being an age-dependent disease, the transgene is expected to cause AD-like symptoms in this porcine model, and the SORT should be repeated at older ages.     

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.