Similarities and differences in spatial learning and object recognition between young male C57Bl/6J mice and Sprague-Dawley rats.

Mice and rats are often used interchangeably in neuroscience research. However, species differences in brain structure and connectivity exist within the medial temporal lobe circuits that contribute to learning and memory. The hippocampus in particular contributes to both spatial learning and recognition memory, but the extent to which rats and mice are comparable in these two cognitive domains remains unclear. To evaluate potential species differences in spatial memory and object recognition, young adult male Sprague–Dawley rats and male C57Bl/6J mice were tested in the water maze and novel object recognition tasks. Following six days of training, with four trials per day, there was no difference in the ability of rats and mice to learn the location of a hidden platform. However, rats performed better than mice on the probe trial, indicative of superior retention. In the novel object preference test, no species differences in recognition memory were detected, although rats spent more time exploring the arena and took longer to approach the objects. These observations suggest that while species differences in spatial memory retention are present, they do not correlate with differences in object recognition memory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sex Differences in the Behavioral Response to Spatial and Object Novelty in Adult C57BL/6 Mice.

The present studies examined sex differences in object localization and recognition in C57BL/6 mice. Experiment 1 measured responses to spatial novelty (object displacement) and object novelty (object substitution). Males strongly preferred displaced and substituted objects over unchanged objects, whereas females showed a preference in only 1 measure of object novelty. Experiment 2 further examined object recognition by presenting mice with 2 identical objects, followed 24 hr or 7 days later by testing with a familiar and a novel object. After 24 hr, males preferentially explored the novel object, whereas females exhibited no such preference. Neither sex displayed a preference for the novel object after 7 days. The data suggest that male mice are superior to females at localizing and recognizing objects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Understanding developmental changes in the stability and flexibility of spatial categories based on object relatedness.

Two experiments examined the flexibility and stability with which children and adults organize locations into categories on the basis of object relatedness. Seven-, 9-, and 11-year-olds and adults learned the locations of 20 objects belonging to 4 categories. Displacement patterns revealed that children and adults used object cues to organize the locations into groups. The organization remained the same following a 7-day delay for all 4 ages, demonstrating stability. Moreover, for 11-year-olds and adults, this organization shifted after a new pattern of object-location pairings was introduced. The pattern was less clear for the younger children, suggesting that flexibility increases across childhood. Discussion focuses on the dynamics of organization processes, particularly stability and flexibility, and the integration of objects and locations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacological evidence of the role of dorsal striatum in spatial memory consolidation in mice.

This study investigated the role of dorsal striatum in spatial memory in mice. The mice were tested for their ability to detect a spatial displacement 24 hrs after training. In order to manipulate the dorsal striatum, focal administrations of the N-methyl-D-aspartate (NMDA) antagonist D-2-amino-5 phosphonopentanoic acid (AP-5) were performed immediately after training. AP-5 impaired the mice's ability to detect the spatial change only if their initial position was constant during training and testing. These findings demonstrate that NMDA receptor blockade within the dorsal striatum impairs spatial memory consolidation in a task in which no explicit reward or procedural learning is involved. The results are discussed with reference to a possible selective involvement of this structure in processing spatial information acquired through an egocentric, but not an allocentric, frame of reference. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys.

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Prefrontal contributions to delayed spatial and object alternation: A positron emission tomography study.

Delayed alternation tasks are frequently used as probes of frontal lobe functioning. To clarify the neural substrates of delayed alternation performance in humans, the authors measured regional cerebral blood flow with H?1?O positron emission tomography in healthy subjects as they performed delayed spatial and object alternation. Consistent with the monkey lesion literature, increased dorsolateral prefrontal activity emerged during delayed spatial alternation but not delayed object alternation, whereas orbitofrontal activations emerged in both alternation tasks. The possible cognitive processes contributing to the orbitofrontal and dorsolateral prefrontal involvement in delayed alternation are discussed. Additional activations localized to several nonfrontal. regions suggest caution in interpreting alternation deficits in patients as strictly reflecting frontal lobe impairment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extinction, renewal, and spontaneous recovery of a spatial preference in the water maze.

Four experiments with C57BL/6 mice investigated extinction of a spatial preference in the Morris water maze. In Experiment 1, a spatial preference was extinguished by exposing mice to the water maze in the absence of a platform but in the presence of the distal spatial cues. In Experiment 2, extinction occurred when the platform was removed from the pool, when it was presented in random locations, or when it was presented consistently in the opposite location. Contextual renewal (Experiment 3) and spontaneous recovery (Experiment 4) of spatial preferences argue against an interpretation of extinction in terms of unlearning and instead suggest that extinction in the water maze, like extinction in Pavlovian conditioning, suppresses the original association. Implications of these findings for theories of spatial learning and hippocampal function are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increase of locomotor activity underlying the behavioral disinhibition in Tg2576 mice.

The transgenic Tg2576 mouse is a widely used animal model that develops some of the cognitive and neuropathological deteriorations observed in patients suffering Alzheimer's disease. The authors investigated 9-month-old Tg2576 mice with respect to behavioral and endocrinological (hypothalamic- pituitary-adrenal [HPA] axis activity) parameters. The locomotor activity test revealed that Tg2576 mice moved almost twice as much as controls. Tg2576 mice spent significantly more time visiting the open arms and performed more entries into these open arms than did controls. However, the amount of time that Tg2576 mice remained in each entry to the open arm was similar to that of controls, and the number of arm entries correlated positively to locomotor activity. In the forced swimming test, Tg2576 mice showed a significant decrease in immobility time, which correlated negatively to locomotor activity. Parameters of the HPA axis, such as plasma level of corticosterone, adrenal gland weight, and noradrenaline or adrenaline release, did not differ between controls and Tg2576 mice. These data suggest that the disinhibitory behavior of Tg2576 mice seems to be related to increased locomotor activity but not to any disturbance of the HPA axis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running.

The hippocampus is important for the acquisition of new memories. It is also one of the few regions in the adult mammalian brain that can generate new nerve cells. The authors tested the hypothesis that voluntary exercise increases neurogenesis and enhances spatial learning in mice selectively bred for high levels of wheel running (S mice). Female S mice and outbred control (C) mice were housed with and without running wheels for 40 days. 5-Bromodeoxyuridine was used to label dividing cells. The Morris water maze was used to measure spatial learning. C runners showed a strong positive correlation between running distance and new cell number, as well as improved learning. In S runners, neurogenesis increased to high levels that reached a plateau, but no improvement in learning occurred. This is the first evidence that neurogenesis can occur without learning enhancement. The authors propose an alternative function of neurogenesis in the control of motor behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estradiol-induced enhancement of object memory consolidation involves NMDA receptors and protein kinase A in the dorsal hippocampus of female C57BL/6 mice.

This study examined the role of dorsal hippocampal NMDA receptors and PKA activation in 17β-estradiol (E?)-induced enhancement of object memory consolidation. Mice explored two identical objects during training, after which they immediately received intraperitoneal injections of 0.2 mg/kg E?, and bilateral dorsal hippocampal infusions of Vehicle, the NMDA receptor antagonist APV (2.5 μg/side), or the cAMP inhibitor Rp-cAMPS (18.0 μg/side). Retention was tested 48 hours later. The enhanced object memory and increased ERK phosphorylation observed with E? alone was reduced by APV and Rp-cAMPS, suggesting that estrogenic enhancement of object memory involves NMDA receptors and PKA activation within the dorsal hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral and neurobiological changes in C57BL/6 mice exposed to cuprizone.

C57BL/6 mice were given 0.2% cuprizone (CPZ) for 2 to 6 weeks while controls ate the same diet without CPZ. At various time points the animals were subjected to behavioral tests and their brains were analyzed. Mice exposed to CPZ for 2 and 3 weeks displayed more climbing behavior and lower prepulse inhibition, suggesting an increase in central nervous system activity and impaired sensorimotor gating. In addition, they showed lower activities of monoamine oxidase and dopamine beta hydroxylase in the hippocampus and prefrontal cortex, and had higher dopamine but lower norepinephrine levels in the prefrontal cortex. Mice exposed to CPZ for 4 to 6 weeks had less social interaction, which is an animal correlate of social withdrawal of patients with schizophrenia. Also, these CPZ-exposed mice showed evident brain demyelination, myelin break down, and loss of oligodendrocytes. At all time points the CPZ-exposed mice spent more time in the open arms of an elevated plus maze and exhibited spatial working memory impairment. These data are in line with evidence from human studies suggesting a putative role of white matter abnormality in the pathophysiology of schizophrenia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Physical activity and cognitive function in a cross-section of younger and older community-dwelling individuals.

Previous reports have indicated a small, positive relationship between physical activity and cognition. However, the majority of research has focused on older adults, with few studies examining this relationship during earlier periods of the life span. This study examined the relationship of physical activity to cognition in a cross-section of 241 community-dwelling individuals 15-71 years of age with a task requiring variable amounts of executive control. Data were analyzed with multiple regression, which controlled for age, sex, and IQ. Participants reported their physical activity behavior and were tested for reaction time (RT) and response accuracy on congruent and incongruent conditions of a flanker task, which manipulates interference control. After controlling for confounding variables, an age-related slowing of RT was observed during both congruent and incongruent flanker conditions. However, physical activity was associated with faster RT during these conditions, regardless of age. Response accuracy findings indicated that increased physical activity was associated with better performance only during the incongruent condition for the older cohort. Findings suggest that physical activity may be beneficial to both general and selective aspects of cognition, particularly among older adults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Haloperidol induced microcatalepsy differs in CD-1, BALB/c, and C57BL/6 mice.

The degree of arrest of movement (microcatalepsy) induced by haloperidol at doses equipotent for operant rate suppression was measured with computerized instrumentation. The inbred C57BU6 mouse strain displayed more susceptibility to microcatalepsy than the CD-1 and BALB/c strains. In addition, the C57BL/6 strain exhibited a greater degree of sensitization to repeated dosing than did the other 2 strains. The results were consistent with the C57BL/6 mouse's hypodopaminergic profile reported in the literature but were at odds with results reported for conventional catalepsy testing. The C57BL/6 mouse may serve as a model for genetic vulnerability to extrapyramidal motor side effects and may be useful in quantifying the mild extrapyramidal motor side effects of atypical antipsychotic drugs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of amiloride on operantly conditioned performance in an NaCl taste detection task and NaCl preference in C57BL/6J mice.

A 2-response operant taste discrimination procedure, modified to assess taste sensitivity in water-restricted C57BL/6J mice, revealed a detection threshold of 0.065 M sodium chloride. Amiloride increased the threshold by –1 log?? unit. These results are the first to demonstrate the necessity of the amiloride-sensitive taste transduction pathway in the normal detection of low concentrations of sodium chloride in mice and provide a functional context in which to evaluate electrophysiological findings. Two-bottle preference tests performed with these mice and additional naive mice revealed only marginal, if any, effects of amiloride on salt intake behavior, highlighting the importance of considering the relative attributes and limitations of different behavioral assays of taste function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Allocentric Coding of Object-to-Object Relations in Overlearned and Novel Environments.

R. F. Wang and E. S. Spelke's (2000) finding that disorientation disrupts knowledge is consistent with egocentric but not allocentric coding of object location. The present experiments tested the hypothesis that egocentric coding may dominate early on but that once an allocentric representation is established, then target location is retrieved from it. This hypothesis predicts that disorientation will disrupt configuration knowledge in a novel environment, such as that used by Wang and Spelke, but not in an overlearned environment. Experiments 1 and 2 tested whether disorientation disrupted configuration knowledge of an overlearned environment, and Experiments 3-7 tested whether disorientation disrupted configuration knowledge of a novel, room-sized environment. In none of the experiments did disorientation disrupt configuration knowledge. Hence, in addition to showing allocentric coding of overlearned interlandmark relations, the present findings are consistent with the immediate availability of allocentric location codes in a novel, room-sized environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired Visuospatial Recognition Memory but Normal Object Novelty Detection and Relative Familiarity Judgments in Adult Mice Expressing the APPswe Alzheimer's Disease Mutation.

The present study examined the effects of a human APPswe mutation on object recognition memory in adult Tg2576 mice. The results showed that 14-month old Tg2576 mice were able to detect object novelty as well as control mice, even with delays of up to 24 hr. In addition, transgenic mice showed a normal recency effect and explored the most recently encountered object significantly less than an object encountered earlier in a trial. However, adult Tg2576 mice showed impairments in detecting a change in the relative positions of an array of familiar objects. The results suggest that the formation of representations involving a combination of object identity and spatial information are particularly sensitive to amyloid pathology in adult APPswe mutant mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: Context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 2 and 3 hr after contextual fear conditioning training. D2 mice showed less freezing at 15 min, 30 min, and 24 hr after training. B6 mice exhibited exaggerated generalized freezing and poor discrimination between the context and altered context 7-30 days after training. The acoustic startle response in B6 mice was also enhanced at 14 days after training. D2 mice did not show this pattern of generalized freezing. B6, but not D2, mice retained contextual memories for at least 60 days. (PsycINFO Database Record (c) 2010 APA, all rights reserved)