Spatial Learning Paradigm Research Articles

Unbiased analysis of spatial learning strategies in a modified Barnes maze using convolutional neural networks

Assessment of spatial learning abilities is central to behavioral neuroscience and a useful tool for animal model validation and drug development. However, biases introduced by the apparatus, environment, or experimentalist represent a critical challenge to the test validity. We have recently developed the Modified Barnes Maze (MBM) task, a spatial learning paradigm that overcomes inherent behavioral biases of animals in the classical Barnes maze. The specific combination of spatial strategies employed by mice is often considered representative of the level of cognitive resources used. Herein, we have developed a convolutional neural network-based classifier of exploration strategies in the MBM that can effectively provide researchers with enhanced insights into cognitive traits in mice. Following validation, we compared the learning performance of female and male C57BL/6J mice, as well as that of Ts65Dn mice, a model of Down syndrome, and 5xFAD mice, a model of Alzheimer’s disease. Male mice exhibited more effective navigation abilities than female mice, reflected in higher utilization of effective spatial search strategies. Compared to wildtype controls, Ts65Dn mice exhibited delayed usage of spatial strategies despite similar success rates in completing this spatial task. 5xFAD mice showed increased usage of non-spatial strategies such as Circling that corresponded to higher latency to reach the target and lower success rate. These data exemplify the need for deeper strategy classification tools in dissecting complex cognitive traits. In sum, we provide a machine-learning-based strategy classifier that extends our understanding of mice’s spatial learning capabilities while enabling a more accurate cognitive assessment.

Intermixed levels of visual search difficulty produce asymmetric probability learning.

When performing novel tasks, we often apply the rules we have learned from previous, similar tasks. Knowing when to generalize previous knowledge, however, is a complex challenge. In this study, we investigated the properties of learning generalization in a visual search task, focusing on the role of search difficulty. We used a spatial probability learning paradigm in which individuals learn to prioritize their search toward the locations where a target appears more often (i.e., high-probable location) than others (i.e., low-probable location) in a search display. In the first experiment, during a training phase, we intermixed the easy and difficult search trials within blocks, and each was respectively paired with a distinct high-probable location. Then, during a testing phase, we removed the probability manipulation and assessed any generalization of spatial biases to a novel, intermediate difficulty task. Results showed that, as training progressed, the easy search evoked a stronger spatial bias to its high-probable location than the difficult search. Moreover, there was greater generalization of the easy search learning than difficult search learning at test, revealed by a stronger bias toward the former's high-probable location. Two additional experiments ruled out alternatives that learning during difficult search itself is weak and learning during easy search specifically weakens learning of the difficult search. Overall, the results demonstrate that easy search interferes with difficult search learning and generalizability when the two levels of search difficulty are intermixed.

Artificial selection for reversal learning reveals limited repeatability and no heritability of cognitive flexibility in great tits (Parus major).

Cognitive flexibility controls how animals respond to changing environmental conditions. Individuals within species vary considerably in cognitive flexibility but the micro-evolutionary potential in animal populations remains enigmatic. One prerequisite for cognitive flexibility to be able to evolve is consistent and heritable among-individual variation. Here we determine the repeatability and heritability of cognitive flexibility among great tits (Parus major) by performing an artificial selection experiment on reversal learning performance using a spatial learning paradigm over three generations. We found low, yet significant, repeatability (R = 0.15) of reversal learning performance. Our artificial selection experiment showed no evidence for narrow-sense heritability of associative or reversal learning, while we confirmed the heritability of exploratory behaviour. We observed a phenotypic, but no genetic, correlation between associative and reversal learning, showing the importance of prior information on reversal learning. We found no correlation between cognitive and personality traits. Our findings emphasize that cognitive flexibility is a multi-faceted trait that is affected by memory and prior experience, making it challenging to retrieve reliable values of temporal consistency and assess the contribution of additive genetic variation. Future studies need to identify what cognitive components underlie variation in reversal learning and study their between-individual and additive genetic components.

Sex Differences in Olfactory Spatial Learning in Postnatal Day 13 Mice (P7-9.012)

<h3>Objective:</h3> Sex differences in the ability of C57BL6/J mice to complete OSL has not been reported. <h3>Background:</h3> Mouse models of early-life brain injury are useful for studying injury to the hippocampus. At postnatal day 13 (P13), there are few methods that assess hippocampal function. At this developmental time point, a mouse’s eyes are still closed and they use olfaction to navigate their environment. The Olfactory Spatial Learning (OSL) paradigm tests whether mouse pups can create an olfactory spatial map to reach a goal containing their littermates. <h3>Design/Methods:</h3> Male and female naive mice were tested on the OSL paradigm at P13, in either a Fixed or an Altered condition. Each corner of the OSL chamber had a cotton swab containing a different scent. Each mouse completed four Training Trials where they could navigate the chamber until they found the goal petri dish containing littermates, or a maximum of 150 seconds. The mouse then completed one Test Trial where the petri dish was removed and the mouse had to navigate to the goal location of the removed petri dish. <h3>Results:</h3> Data passed Shapiro-Wilk test for normality. Mixed-effect analysis revealed significant difference in latency to goal across Training Trials (p&lt;0.05), indicating that mice learn how to reach the goal faster across trials. On the Test Trial, male mice in the Fixed condition reached the goal location faster than male mice in the Altered condition (p&lt;0.05), but this difference was not observed in female mice. <h3>Conclusions:</h3> These data suggest that P13 male mice, but not female mice, exhibit olfactory-dependent spatial learning. This is the first demonstration of sex differences in hippocampal-dependent spatial learning at this young developmental timepoint. Future directions include using OSL to study sex differences in hippocampal function in mouse models of early life brain injury including perinatal hypoxia-ischemia. <b>Disclosure:</b> Miss Doebley has nothing to disclose. Ms. Nicolayevsky has nothing to disclose. Miss Sheyenne Gillis has nothing to disclose. Dr. Yun has nothing to disclose. The institution of Prof. Eisch has received research support from NIH . The institution of Prof. Eisch has received research support from NASA. Prof. Eisch has received personal compensation in the range of $0-$499 for serving as a Study section member with NIH. Prof. Eisch has received personal compensation in the range of $0-$499 for serving as a Grant reviewer with NASA. The institution of Dr. Barber has received research support from NIH.

Using Appetitive Motivation to Train Mice for Spatial Learning in the Barnes Maze.

The Barnes maze, a well-known spatial-learning paradigm, is based on the innate fear of rodents of large open spaces and their drive to hide. However, additional aversive stimuli (strong light and threatening sounds) are often necessary to provoke the hiding response while rendering the method cumbersome and more stressful. Our objective was to establish a Barnes maze-learning paradigm in mice using palatable food as a reward. After habituating male C57BL6/J or NMRI mice to the reward, the experimenter and the apparatus, either a slow (2 trials/day) or a massive conditioning schedule (4 trials/day), was run. Acquisition training was carried out until mice could locate the reward box with a maximum of one hole error. Then, the box was replaced to another location (reversal phase). Mice needed to relearn the new position with the same criterion. One week later, retention trials were performed. Both strains could reach the learning criteria; in the massive training within a shorter period. Spatial memory was demonstrated in the reversal and retention trials. Our results show that palatable food can be used as an efficient motivator to acquire allocentric navigation in the Barnes maze with the additional advantage of being less stressful.

Ameliorative effect of vanillin on scopolamine-induced dementia-like cognitive impairment in a mouse model.

Alzheimer's disease (AD) is the most common form of dementia, which is among the top five causes of death in the United States. It is a neurodegenerative disorder that causes permanent loss of memory and cognition. The current pharmacotherapy for AD is based on providing symptomatic relief only and has many side effects. There is a need for a safer, disease-modifying drug for the treatment of AD. The PASS online software was used to screen phytoconstituents based on their predicted effects on various AD-related targets. Vanillin was selected as the compound of interest, as it has not been researched elaborately on any animal model of AD. The acetylcholinesterase inhibitory activity of vanillin was established in vitro. Thereafter, ameliorative effect of vanillin was evaluated using the exteroceptive memory model in scopolamine-induced cognitive impairment mice model. Vanillin showed an acetylcholinesterase inhibitory activity in vitro, and the IC50 value was calculated to be 0.033 mM. Vanillin significantly reversed the memory and behavioral deficits caused by scopolamine as demonstrated by significant improvement in memory in negative reinforcement, elevated plus maze, and spatial learning paradigms. Vanillin also proved to have a nootropic effect. Also, vanillin proved to have significantly better antioxidant and acetylcholinesterase inhibitory effects in vivo than donepezil hydrochloride. The potential anti-AD activity of vanillin was also confirmed by the reduction in IL-6 levels and TNF-α levels. Our results suggest that vanillin is a safe and effective natural drug candidate having a great potential for the treatment of AD. However, more research is required to evaluate its effect on A beta plaques and Tau neurofibrillary tangles in vivo.

ΔFosB accumulation in hippocampal granule cells drives cFos pattern separation during spatial learning

Mice display signs of fear when neurons that express cFos during fear conditioning are artificially reactivated. This finding gave rise to the notion that cFos marks neurons that encode specific memories. Here we show that cFos expression patterns in the mouse dentate gyrus (DG) change dramatically from day to day in a water maze spatial learning paradigm, regardless of training level. Optogenetic inhibition of neurons that expressed cFos on the first training day affected performance days later, suggesting that these neurons continue to be important for spatial memory recall. The mechanism preventing repeated cFos expression in DG granule cells involves accumulation of ΔFosB, a long-lived splice variant of FosB. CA1 neurons, in contrast, repeatedly expressed cFos. Thus, cFos-expressing granule cells may encode new features being added to the internal representation during the last training session. This form of timestamping is thought to be required for the formation of episodic memories.

MiR-124 protects against cognitive dysfunction induced by sevoflurane anesthesia in vivo and in vitro through targeting calpain small subunit 1 via NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is an impairment of cognition that affects post-surgery patients. Sevoflurane anesthesia is linked to cognitive dysfunction correlated to the expression of miRNA levels. In the current study, we investigated if miR-124 can offer protection against cognitive deficits induced by sevoflurane in a spatial learning paradigm, and examined the molecular mechanisms through cell cultures. Escape latency, platform crossings in probe trials and swimming speed in the Morris water maze in sevoflurane-treated mice were utilized as a measure of cognitive function. The relative miR-124 expression, and mRNA expressions of Bax, caspase-3 and Bcl-2 in sevoflurane-treated hippocampal cultures were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, the changes in interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α) and IL-6 were determined using enzyme-linked immunosorbent assay (ELISA). The binding between miR-124 and calpain small subunit 1 (Capn4) was verified with site-directed mutagenesis. The involvement of the nuclear factor kappa B (NF-κB) signaling pathway was examined using western blot analysis. Our findings indicated that the miR-124 expression was inhibited by sevoflurane treatment in live rats and mouse hippocampal neurons to prevent apoptosis and inflammatory responses. We confirmed Capn4 as a target of miR-124. Treatment with sevoflurane enhanced the expression of Capn4, while overexpression of miR124 suppressed the enhanced expression of Capn4. Also, miR-124 inhibited apoptosis in murine hippocampal neurons induced by sevoflurane via the NF-κB signaling pathway. Our findings demonstrated that miR-124 exerted its neuroprotective role against sevoflurane via targeting Capn4 and NF-κB signaling pathways. Our work may provide a novel and efficacious treatment for sevoflurane anesthesia-related cognitive dysfunction.

Unraveling Early Signs of Navigational Impairment in APPswe/PS1dE9 Mice Using Morris Water Maze.

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.

Spatial Learning in Japanese Eels Using Extra- and Intra-Maze Cues.

Japanese eels (Anguilla japonica) were trained on a spatial-learning paradigm in a pool placed in an experimental room where several extra-maze cues were present. Four tubes were placed in the pool, of which one was open and could be entered by the eels. The open tube was placed at a fixed position in the pool and contained a triangular block that served as an intra-maze cue. The eels learned to identify the open tube, and their performance was maintained when the pool was rotated. However, they were unable to maintain their performance in a dark room, which suggests that spatial learning is based on visual cues. To determine the influence of the extra- and intra-maze cues, the tube with the triangle was moved to a new position and another open tube was kept in its place. The eels chose either the tube at the original position or the tube with the triangle at its new position, suggesting that spatial discrimination may be based on either extra- or intra-maze cues. We thus conclude that the eels employed an adjunctive strategy of multiple cues. In the next experiment, the eels were trained to visually discriminate the position of the stimulus (triangle), which changed in every trial. After the training, the eels were submitted to a test in which, in addition to the triangular pattern, a rectangular pattern was introduced. The eels discriminated between the tubes with the triangular and rectangular patterns, suggesting that they had the ability to discriminate visual patterns.

Modifications to cytoskeleton-associated proteins in dendritic spines underlie the adaptive plasticity involved in long term reference memory

Spatial learning and memory enables individuals to orientate themselves in an external environment. Synaptic stimulation of dendritic spines on hippocampal place cells underlies adaptive cognitive performance, inducing plastic changes such as spinogenesis, pruning and structural interconversion. Such plastic changes are driven by complex molecular machinery that relies on several actin cytoskeleton-associated proteins (ACAP's), these interacting with actin filaments in the postsynaptic density to guide the conformational changes to spines in accordance with the synaptic information they receive. However, the specific dynamics of the plastic changes in spines driven by ACAP's are poorly understood. Adult rats exhibit efficient allocentric reference memory 30days after training in a spatial learning paradigm in the Morris water maze. A Golgi study revealed this behavior to be associated with a reduction in both spine density and in mushroom spines, as well as a concomitant increase in thin spines. These changes were accompanied by the overexpression of mRNA encoding β-actin, Spinophilin and Cortactin, whilst the expression of Profilin, α-actinin, Drebrin, Synaptopodin and Myosin decreased. By contrast, no changes were evident in Cofilin, Gelsolin and Arp2/3 mRNA. From this analysis, it appears that neither spinogenesis nor new mushroom spines are necessary for long-term spatial information retrieval, while thin spines could be potentiated to retrieve pre-learned spatial information. Further studies that focus on the signaling pathways and their related molecules may shed further light on the molecular dynamics of the plastic changes to dendritic spines that underlie cognitive performance, both under normal and pathological conditions.

The Environmental Geometry in Spatial Learning by Zebrafish (Danio rerio).

During navigation, disoriented animals learn to use the spatial geometry of rectangular environments to gain rewards. The length of macroscopic surfaces (metric: short/long) and their spatial arrangement (sense: left/right) are powerful cues that animals prove to encode for reorientation. The aim of this study was to investigate if zebrafish (Danio rerio) could take advantage of such geometric properties in a rewarded exit task, by applying a reference memory procedure. The experiment was performed in a rectangular arena having four white walls, where fish were required to choose the two geometrically equivalent exit corners lying on the reinforced diagonal. Results showed that zebrafish encoded the geometry of the arena during reorientation, solving the spatial task within the first 5 days of training. With the aim to avoid the possible influence of extravisual cues on the zebrafish success, we performed a geometric test in extinction of response after the learning day. At test, fish persisted in choosing the two correct corners, thus confirming that the navigation strategy used at training was based on geometric cues. This study adds evidence about the role of geometric frameworks in fish species, and it further validates an effective spatial learning paradigm for zebrafish.

Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory.

The notion of "immune privilege" of the brain has been revised to accommodate its infiltration, at steady state, by immune cells that participate in normal neurophysiology. However, the immune mechanisms that regulate learning and memory remain poorly understood. Here, we show that noninflammatory interleukin-17 (IL-17) derived from a previously unknown fetal-derived meningeal-resident γδ T cell subset promotes cognition. When tested in classical spatial learning paradigms, mice lacking γδ T cells or IL-17 displayed deficient short-term memory while retaining long-term memory. The plasticity of glutamatergic synapses was reduced in the absence of IL-17, resulting in impaired long-term potentiation in the hippocampus. Conversely, IL-17 enhanced glial cell production of brain-derived neurotropic factor, whose exogenous provision rescued the synaptic and behavioral phenotypes of IL-17-deficient animals. Together, our work provides previously unknown clues on the mechanisms that regulate short-term versus long-term memory and on the evolutionary and functional link between the immune and nervous systems.

Spatial Learning Paradigm Can Increase Post-Stress Total Time of REM Sleep in Immobilized Rats

Spatial Learning Paradigm Can Increase Post-Stress Total Time of REM Sleep in Immobilized Rats

LY379268 Does Not Have Long-Term Procognitive Effects nor Attenuate Glutamatergic Signaling in AβPP/PS1 Mice.

Chronically elevated basal glutamate levels are hypothesized to attenuate detection of physiological signals thereby inhibiting memory formation and retrieval, while inducing excitotoxicity-mediated neurodegeneration observed in Alzheimer's disease (AD). However, current medication targeting the glutamatergic system, such as memantine, shows limited efficacy and is unable to decelerate disease progression, possibly because it modulates postsynaptic N-methyl-D-aspartate receptors rather than glutamate release or clearance. To determine if decreasing presynaptic glutamate release leads to long-term procognitive effects, we treated AβPP/PS1 mice with LY379268 (3.0 mg/kg; i.p.), a metabotropic glutamate receptor (mGluR)2/3 agonist from 2-6 months of age when elevated glutamate levels are first observed but cognition is unaffected. C57BL/6J genetic background control mice and another cohort of AβPP/PS1 mice received normal saline (i.p.) as vehicle controls. After 6 months off treatment, mice receiving LY379268 did not show long-term improvement as assessed by the Morris water maze (MWM) spatial learning and memory paradigm. Following MWM, mice were isoflurane anesthetized and a glutamate selective microelectrode was used to measure in vivo basal and stimulus-evoked glutamate release and clearance independently from the dentate, CA3, and CA1 hippocampal subregions. Immunohistochemistry was used to measure hippocampal astrogliosis and plaque pathology. Similar to previous studies, we observed elevated basal glutamate, stimulus evoked glutamate release, and astrogliosis in AβPP/PS1 vehicle mice versus C57BL/6J mice. Treatment with LY379268 did not attenuate these responses nor diminish plaque pathology. The current study builds upon previous research demonstrating hyperglutamatergic hippocampal signaling in AβPP/PS1 mice; however, long-term therapeutic efficacy of LY379268 in AβPP/PS1 was not observed.

Non-motor Behavioral Alterations of PGC-1α-Deficient Mice - A Peculiar Phenotype With Slight Male Preponderance and No Apparent Progression.

Dysfunction of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) has been linked to various neurodegenerative and neuropsychiatric disorders; however, reports on psychic behavioral alterations on PGC-1α-deficient animals are sparse. The present study revisited prior observations of anxiety-related, depression-related, and hippocampal memory-related observations having been made on different PGC-1α-deficient murine strains, in a large-scale analysis on whole-body full-length (FL-)PGC-1α-deficient mice. The examinations were performed on animals covering a wide age range enrolled from both sexes, and included paradigms such as the open-field, elevated plus maze, light-dark box, tail suspension test, and spatial recognition two-trial Y-maze. The findings revealed no signs of previously reported anxiety-like behavior, but revealed an unexpected phenotype with decreased anxiety behavior consistent throughout different paradigms, with slight male preponderance. This was associated with despair-like anhedonic behavior, consistent with that reported previously, but did not associate with either peripheral or brain alterations in kynurenic acid synthesis, which was previously proposed. Though male FL-PGC-1α-deficient mice tended to perform poorer in the hippocampus-based spatial learning paradigm, the genotype overall was not associated with impairment in spatial memory, contradicting with prior observations. None of the observed alterations deteriorated with age, similarly to motor alterations as reported previously. The most likely contributors of this peculiar phenotype are discussed, with clinicopathological correlations drawn. Being the first to address these behavioral domains within the same PGC-1α-deficient strain, our findings extend the knowledge about the complex in vivo effect of PGC-1α dysfunction and add important notes to research in the field of PGC-1α in connection with neuropsychiatric disorders.

Negative transfer effects between reference memory and working memory training in the water maze in C57BL/6 mice

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals – regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended.

Predictably harsh environment is associated with reduced cognitive flexibility in wild food-caching mountain chickadees

Cognition is one of the mechanisms underlying behavioural flexibility, but flexibility of cognition itself may vary as a result of trade-offs between the ability to learn new information and the ability to retain old memories. How and when cognitive flexibility is constrained by this trade-off remains poorly understood. We investigated cognitive flexibility in wild food-caching mountain chickadees, Poecile gambeli, at different elevations experiencing different levels of environmental harshness during the nonbreeding season, using a spatial learning and memory reversal paradigm. There were no significant differences in sampling strategies between elevations, but high-elevation chickadees performed worse than low-elevation chickadees on the reversal task, indicating lower cognitive flexibility. Compared to the initial learning task, low-elevation chickadees improved their performance during the reversal task, while high-elevation chickadees performed worse. High-elevation birds inspected previously rewarding locations more frequently than other locations, suggesting that reduced cognitive flexibility is associated with proactive interference. Considering that high-elevation chickadees cache more food and are likely more dependent on these caches than their conspecifics from low elevation, and that chickadees from both elevations use similar sampling strategies, our findings suggest that stronger memories of more caches might interfere with acquisition and retention of new memories. Overall, our results suggest that predictably harsh environments might favour stronger memories at the expense of decreased cognitive flexibility, which is likely driven by increased proactive interference.

The Effects of Restricted Peripheral Field-of-View on Spatial Learning while Navigating.

Recent work with simulated reductions in visual acuity and contrast sensitivity has found decrements in survey spatial learning as well as increased attentional demands when navigating, compared to performance with normal vision. Given these findings, and previous work showing that peripheral field loss has been associated with impaired mobility and spatial memory for room-sized spaces, we investigated the role of peripheral vision during navigation using a large-scale spatial learning paradigm. First, we aimed to establish the magnitude of spatial memory errors at different levels of field restriction. Second, we tested the hypothesis that navigation under these different levels of restriction would use additional attentional resources. Normally sighted participants walked on novel real-world paths wearing goggles that restricted the field-of-view (FOV) to severe (15°, 10°, 4°, or 0°) or mild angles (60°) and then pointed to remembered target locations using a verbal reporting measure. They completed a concurrent auditory reaction time task throughout each path to measure cognitive load. Only the most severe restrictions (4° and blindfolded) showed impairment in pointing error compared to the mild restriction (within-subjects). The 10° and 4° conditions also showed an increase in reaction time on the secondary attention task, suggesting that navigating with these extreme peripheral field restrictions demands the use of limited cognitive resources. This comparison of different levels of field restriction suggests that although peripheral field loss requires the actor to use more attentional resources while navigating starting at a less extreme level (10°), spatial memory is not negatively affected until the restriction is very severe (4°). These results have implications for understanding of the mechanisms underlying spatial learning during navigation and the approaches that may be taken to develop assistance for navigation with visual impairment.

Expression regulation and targeting of the peroxisome proliferator-activated receptor γ following electrically-induced status epilepticus

The neuroprotective and anti-inflammatory effects of the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone are of particular interest for disease-modifying and antiepileptogenic approaches. We studied the expression of PPARγ and the impact of rosiglitazone on the consequences of status epilepticus (SE) in a rat post-SE model. Immunohistochemical analysis revealed a selective overexpression of PPARγ in the piriform cortex of rats with spontaneous seizures. Rosiglitazone administration initiated following SE failed to exert relevant effects on the development of spontaneous seizures and neuronal cell loss. Whereas spatial learning in the Morris water maze was delayed in SE animals with vehicle administration, the learning curve of rosiglitazone-treated SE rats showed no significant difference to that of controls. The study provides first evidence arguing against a robust antiepileptogenic effect. However, the findings in the spatial learning paradigm indicate disease-modifying effects.