Impaired "episodic-like" object memory in adult APPswe transgenic mice.

An early clinical symptom of Alzheimer's disease is impaired episodic memory. However, the precise pathological event(s) that underpins this deficit remains unclear. In the present study, the authors examined whether wild-type mice and Tg2576 mice expressing an amyloid precursor protein (APP) mutation are able to form an integrated memory of the spatio-temporal context in which objects are presented. In Experiment 1, wild-type mice, but not Tg2576 mice that were 10-12 months old, explored objects presented in a novel location. In Experiment 2, wild-type mice explored an object that was presented both earlier in a sequence and in a different location relative to other objects that possessed only one of these properties (i.e., memory for "what," "where," and "when" items were presented). In contrast, the behavior of adult Tg2576 mice was influenced only by the temporal order in which objects were presented. These results demonstrate that wild-type, but not APP-mutant, mice are able to form an "episodic-like" memory of the spatio-temporal properties of objects and support the hypothesis that aberrant APP processing contributes to impairments in event memory. (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)     

Inactivation of sodium channel Scn8A (Nav1.6) in purkinje neurons impairs learning in Morris Water Maze and delay but not trace eyeblink classical conditioning.

To examine the isolated effects of altered currents in cerebellar Purkinje neurons, the authors used Scn8aflox/flox, Purkinje cell protein-CRE (Pcp-CRE) mice in which Exon 1 of Scn8a is deleted only in Purkinje neurons. Twenty male Purkinje Scn8a knockout (PKJ Scn8a KO) mice and 20 male littermates were tested on the Morris water maze (MWM). Subsequently, half were tested in 500-ms delay and half were tested in 500-ms trace eyeblink conditioning. PKJ Scn8a KO mice were impaired in delay conditioning and MWM but not in trace conditioning. These results provide additional support for the necessary participation of cerebellar cortex in normal acquisition of delay eyeblink conditioning and MWM and raise questions about the role, if any, of cerebellar cortex in trace eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin 5-HT1A and 5-HT? receptors in an impulsive–aggressive phenotype.

In adult male hamsters, individual differences in offensive aggression are correlated with differences in impulsive choice and decreased serotonin (5-HT) innervation. As serotonin 1A (5-HT1A) receptors participate in the inhibition of aggression, whereas 5-HT?receptor activation facilitates aggression, the authors hypothesized that differences in their expression are associated with differences in behavior. The authors confirmed previous behavioral associations, using a delay-discounting paradigm with various delays, as high-aggression (H-Agg) hamsters preferred the immediate-reward lever over the delayed-reward lever under most delays, compared with low-aggression (L-Agg) hamsters. Although the authors observed a greater density of 5-HT1A receptor immunoreactivity in H-Agg hamsters within several areas, it appears to be related to a lack of serotonin release, as supported by further observations of decreased immunoreactive perikarya and 5-HT1A receptors in fluoxetine-treated hamsters. Also, 5-HT? receptor density was greater in H-Agg hamsters within select areas. The data indicate a convergence of impulsive and aggressive characteristics to one phenotype that is associated with various aspects of serotonin function, such as serotonin release and differential expression of 5-HT1A and 5-HT? receptors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Correction to Rhodes et al. (2003): Exercise Increases Hippocampal Neurogenesis to High Levels but Does Not Improve Spatial Learning in Mice Bred for Increased Voluntary Wheel Running.

Reports an error in the original article by Justin S. Rhodes, Henriette van Praag, Susan Jeffrey, Isabelle Girard, Gordon S. Mitchell, Theodore Garland Jr., and Fred H. Gage (Behavioral Neuroscience, 2003, Vol. 117, No. 5, pp. 1006-1016. In Figure 3, the symbols representing the "Control runners" and "Selected no wheels" groups were reversed in Panel B. They should match the legend in Panel A: Open circles should appear as solid squares, and solid squares as open circles. (The following abstract of this article originally appeared in record 2003-08567-013.) 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... (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Learning about environmental geometry: A flaw in Miller and Shettleworth's (2007) operant model.

Many studies have examined how humans and other animals reestablish a sense of direction following disorientation in enclosed environments. Results showing that geometric shape of an enclosure is typically encoded, sometimes to the exclusion of featural cues, have led to suggestions that geometry might be encoded in a dedicated geometric module. Recently, Miller and Shettleworth (2007; see record 2007-09968-001) proposed that the reorientation task be viewed as an operant task and they presented an associative operant model that appears to account for many empirical findings from reorientation studies. In this paper we show that, although Miller and Shettleworth's insights into the operant nature of the reorientation task may be sound, their mathematical model has a serious flaw. We present simulations to illustrate the implications of the flaw. We also propose that the output of a simple neural network, the perceptron, can be used to conduct operant learning within the reorientation task and can solve the problem in Miller and Shettleworth's model. (PsycINFO Database Record (c) 2010 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)     

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)     

Somatosensory Processing and Schizophrenia Liability: Proprioception, Exteroceptive Sensitivity, and Graphesthesia Performance in the Biological Relatives of Schizophrenia Patients.

In the present study, the authors examined somatosensory processing in 30 biological relatives of persons with schizophrenia (hereafter called "schizophrenia relatives"), 30 biological relatives of persons with bipolar affective disorder (psychiatric family control subjects), and 30 healthy control subjects with no family history of psychopathology. All 3 groups completed a weight discrimination task, a 2-point discrimination task, and a complex cognitive somatosensory task (i.e., graphesthesia). The schizophrenia relatives performed significantly worse on all 3 somatosensory tasks compared with both the healthy control subjects and the bipolar relatives. The healthy control subjects and psychiatric family control subjects showed no significant differences on any of the somatosensory tasks. Within the weight discrimination and 2-point discrimination tasks, schizophrenia relatives showed group differences on the d' index, the measure of sensitivity, whereas all 3 groups did not differ on lnβ, the measure of response bias, suggesting a genuine difference in weight and touch sensitivity. The d' value of the weight discrimination task was significantly associated with both the cognitive-perceptual factor and negative symptom factor of the clinical questionnaire (e.g., Schizotypal Personality Questionnaire; SPQ), whereas the 2-point discrimination d' value and graphesthesia scores were significantly associated only with the cognitive-perceptual factor of the SPQ. Implications for the possible relation between somatosensory task performance and schizophrenia liability are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive decline and human (Homo sapiens) aging: An investigation using a comparative neuropsychological approach.

Using a comparative neuropsychological approach, the authors compared performance of younger and healthy older adults ages 65 and over on tasks originally developed to measure cognition in animals. A battery of 6 tasks was used to evaluate object discrimination, egocentric spatial abilities, visual and spatial working memory, and response shifting. Older adults performed more poorly than younger adults on tasks that evaluate egocentric spatial abilities, response shifting, and to a lesser extent object recognition. The two groups did not differ for tasks that evaluate spatial working memory and object discrimination. The impairments the authors observed in tasks that evaluate response shifting and object recognition are consistent with those found in canines and primates as well as those found in Alzheimer's disease. The results are consistent with the notion that cognitive processes supported by the amygdala and the orbitofrontal cortex are among the first to decline with increasing age in both humans and animals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

How do room and apparatus cues control navigation in the Morris water task? Evidence for distinct contributions to a movement vector.

The present study compared the relative influence of location and direction on navigation in the Morris water task. Rats were trained with a fixed hidden or cued platform, and probe trials were conducted with the pool repositioned such that the absolute spatial location of the platform was centered in the opposite quadrant of the pool. Rather than swimming to the platform location, rats swam in the direction that was reinforced during training, resulting in navigation to the relative location of the platform in the pool and search at the appropriate distance from the pool wall. Pool relocation tests revealed disruptions in cued navigation if the cued platform remained at the absolute location, whereas no disruption was observed if the platform remained at the relative location (same direction). The results indicate that direction holds greater influence than does location and further demonstrate that this observation is not altered by the amount of training or time on the platform. The authors propose that navigation in the water task involves a movement vector in which the distal cues and apparatus provide direction and distance information, respectively. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploratory Activity and Fear Conditioning Abnormalities Develop Early in R6/2 Huntington's Disease Transgenic Mice.

The Huntington's disease R6/2 transgenic mouse model, containing exon 1 of the human huntingtin gene with a greatly increased CAG repeat length, shows multiple effects of the altered polyglutamine in the resultant protein. The authors report that exploratory and fear conditioning behavioral changes appear well before the onset of obvious pathology. The first differences in exploratory and fear conditioning behavior emerge by 4 and 5 weeks of age, respectively. These behaviors correlate with the earliest neurochemical and molecular changes previously reported and provide insight into functional mechanisms by which cellular and subcellular disease changes may mediate neurological symptoms. These studies provide behavioral protocols suitable for high-throughput screening of therapeutic agents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased maternal corticosterone levels in rats: Effects on brain 5-HT1A receptors and behavioral coping with stress in adult offspring.

This study examined the consequences of elevated corticosterone levels in lactating rats on their offspring's serotonergic 5-hydroxytryptamine (5-HT)1A receptor system and behavioral coping with stress. The mothers received normal drinking water or water with corticosterone, which, via the milk, enters the circulation and brains of the pups, In adulthood, the corticosterone-nursed offspring showed a consistently more passive way of coping with environmental challenges. However, they did not seem to be more anxious. Autoradiographic analysis of the 5-HT1A receptor system revealed a decrease in the adult 5-HT1A receptor binding in the hippocampal CAI region. The results support the hypothesis that differences in behavioral coping with stress by adult rats are associated with differences in the serotonergic system. At the same time, it suggests that adult coping and its neuronal substrates are not solely determined by genes but depend on subtle developmental factors as well. (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)     

Inhibitory Control and Response Selection in Problem Solving: How Cotton-Top Tamarins (Saguinus oedipus) Overcome a Bias for Selecting the Larger Quantity of Food.

When presented with a choice between 1 and 3 pieces of food in a type of reversed contingency task, 4 cotton-top tamarins (Saguinus oedipus) consistently chose the 3 pieces of food and received nothing, even though the choice of 1 piece would have yielded 3. However, in a task in which the tamarins received the 1 piece of food when they chose it, all subjects learned to select 1 over 3. Thus, the tamarins' prior failure on the reversed contingency task did not result entirely from an inherent inability to suppress the prepotent response of reaching to the larger of 2 quantities of food. After the experience of selecting the smaller quantity and receiving it, all of the tamarins solved the version of the reversed contingency task that they failed initially. These results suggest that the tamarins' initial failure may have reflected a difficulty with selecting an alternative response option. (PsycINFO Database Record (c) 2010 APA, all rights reserved)