Stereotypical Hippocampal Clustering Predicts Navigational Success in Virtualized Real-World Environments.

Structural differences along the hippocampal long axis are believed to underlie meaningful functional differences. Yet, recent data-driven parcellations of the hippocampus subdivide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where male and female participants were trained to virtually navigate a novel neighborhood in a Google Street View-like environment. Participants were scanned while navigating routes early in training and after a 2 week training period. Using the 10-cluster map as the ideal template, we found that participants who eventually learn the neighborhood well have hippocampal cluster maps consistent with the ideal-even on their second day of learning-and their cluster mappings do not deviate over the 2 week training period. However, participants who eventually learn the neighborhood poorly begin with hippocampal cluster maps inconsistent with the ideal template, though their cluster mappings may become more stereotypical after the 2 week training. Interestingly this improvement seems to be route specific: after some early improvement, when a new route is navigated, participants' hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure and instead is driven by a combination of anatomy, task, and, importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral axes.

Enhanced NMDA receptor pathway and glutamate transmission in the hippocampal dentate gyrus mediate the spatial learning and memory impairment of obese rats.

Obesity has been linked with the impairment of spatial memory and synaptic plasticity but the molecular mechanisms remained unidentified. Since glutamatergic transmission and NMDA receptor neural pathways in hippocampal dentate gyrus (DG) are essential in the learning and memory, we aimed to investigate glutamate (Glu) and NMDA receptor signaling of DG in spatial learning and memory in diet-induced obesity (DIO) rats. Spatial learning and memory were assessed via Morris water maze (MWM) test on control (Ctr) and DIO rats. Extracellular concentration of Glu in the DG was determined using in vivo microdialysis and HPLC. The protein expressions of NMDA receptor subunit 2B (NR2B), brain-derived neurotrophic factor (BDNF), the activation of calcium/calmodulin-dependent kinase II (CaMKII) and cAMP-response-element-binding protein (CREB) in the DG were observed by western blot. Spatial learning and memory were impaired in DIO rats compared to those of Ctr. NR2B expression was increased, while BDNF expression and CaMKII and CREB activation were decreased in DG of DIO rats. Extracellular concentration of Glu was increased in Ctr on the 3rd and 4th days of the MWM test, but significant further increment was observed in DIO rats. Microinjection of an NMDA antagonist (MK-801) into the DG reversed spatial learning and memory impairment. Such effects were accompanied by greater BDNF expression and CaMKII/CREB activation in the DG of DIO rats. In conclusion, the enhancement of Glu-NMDA receptor transmission in the hippocampal DG contributes to the impairment of spatial learning and memory in DIO rats, maybe via the modulation of CaMKII-CREB-BDNF signaling pathway.

Cerebral hypoperfusion exacerbates traumatic brain injury in male but not female mice.

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.

The effects of estrogens on spatial learning and memory in female rodents - A systematic review and meta-analysis.

Estrogens have inconsistent effects on learning and memory in both the clinical and preclinical literature. Preclinical literature has the advantage of investigating an array of potentially important factors contributing to the varied effects of estrogens on learning and memory, with stringently controlled studies. This study set out to identify specific factors in the animal literature that influence the effects of estrogens on cognition, for possible translation back to clinical practice. The literature was screened and studies meeting strict inclusion criteria were included in the analysis. Eligible studies included female ovariectomized rodents with an adequate vehicle for the estrogen treatment, with an outcome of spatial learning and memory in the Morris water maze. Training days of the Morris water maze were used to assess acquisition of spatial learning, and the probe trial was used to evaluate spatial memory recall. Continuous outcomes were pooled using a random effects inverse variance method and reported as standardized mean differences with 95 % confidence intervals. Subgroup analyses were developed a priori to assess important factors. The overall analysis favoured treatment for the later stages of training and for the probe trial. Factors including the type of estrogen, route, schedule of administration, age of animals, timing relative to ovariectomy, and duration of treatment were all found to be important. The subgroup analyses showed that chronic treatment with 17ß-estradiol, either cyclically or continuously, to young animals improved spatial recall. These results, observed in animals, can inform and guide further clinical research on hormone replacement therapy for cognitive benefits.

Intracranial self-stimulation reverses impaired spatial learning and regulates serum microRNA levels in a streptozotocin-induced rat model of Alzheimer disease.

BACKGROUND: The assessment of deep brain stimulation (DBS) as a therapeutic alternative for treating Alzheimer disease (AD) is ongoing. We aimed to determine the effects of intracranial self-stimulation at the medial forebrain bundle (MFB-ICSS) on spatial memory, neurodegeneration, and serum expression of microRNAs (miRNAs) in a rat model of sporadic AD created by injection of streptozotocin. We hypothesized that MFB-ICSS would reverse the behavioural effects of streptozotocin and modulate hippocampal neuronal density and serum levels of the miRNAs. METHODS: We performed Morris water maze and light-dark transition tests. Levels of various proteins, specifically amyloid-ß precurser protein (APP), phosphorylated tau protein (pTAU), and sirtuin 1 (SIRT1), and neurodegeneration were analyzed by Western blot and Nissl staining, respectively. Serum miRNA expression was measured by reverse transcription polymerase chain reaction. RESULTS: Male rats that received streptozotocin had increased hippocampal levels of pTAU S202/T205, APP, and SIRT1 proteins; increased neurodegeneration in the CA1, dentate gyrus (DG), and dorsal tenia tecta; and worse performance in the Morris water maze task. No differences were observed in miRNAs, except for miR-181c and miR-let-7b. After MFB-ICSS, neuronal density in the CA1 and DG regions and levels of miR-181c in streptozotocin-treated and control rats were similar. Rats that received streptozotocin and underwent MFB-ICSS also showed lower levels of miR-let-7b and better spatial learning than rats that received streptozotocin without MFB-ICSS. LIMITATIONS: The reversal by MFB-ICSS of deficits induced by streptozotocin was fairly modest. CONCLUSION: Spatial memory performance, hippocampal neurodegeneration, and serum levels of miR-let-7b and miR-181c were affected by MFB-ICSS under AD-like conditions. Our results validate the MFB as a potential target for DBS and lend support to the use of specific miRNAs as promising biomarkers of the effectiveness of DBS in combatting AD-associated cognitive deficits.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

Impact of Sleep Deprivation on the Brain's Inflammatory Response Triggered by Lipopolysaccharide and Its Consequences on Spatial Learning and Memory and Long-Term Potentiation in Male Rats.

INTRODUCTION: Both sleep deprivation (SD) and inflammation can negatively affect cognitive function. This study aimed to investigate how SD impacts the brain's inflammatory response to lipopolysaccharide (LPS) and its subsequent effects on cognitive functions. METHODS: To this end, male rats were tested through a Morris water maze (MWM) to assess their spatial learning and memory. Also, in vivo field potential recordings (to evaluate synaptic plasticity) were done in the Saline, SD, LPS1 (1 mg/kg/7 days), and LPS1+SD groups. Cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Based on the results, the LPS1+SD group showed increased total distance and escape latency compared to the other groups in the MWM test. Besides, the LPS1+SD group exhibited a significant decrease in long-term potentiation (LTP) induction and maintenance in the CA1 area of the brain. Finally, the inflammatory cytokine interleukin-1ß (IL-1ß) levels were significantly higher in the LPS1+SD group than in the Saline group. CONCLUSION: These findings suggest that the combined effects of SD and brain inflammatory response can have more harmful effects on cognitive function, LTP, and inflammatory factors than either SD or LPS1 alone.

Visual artificial grammar learning across 1 year in 7-year-olds and adults.

Acquiring sequential information is of utmost importance, for example, for language acquisition in children. Yet, the long-term storage of statistical learning in children is poorly understood. To address this question, 27 7-year-olds and 28 young adults completed four sessions of visual sequence learning (Year 1). From this sample, 16 7-year-olds and 20 young adults participated in another four equivalent sessions after a 12-month-delay (Year 2). The first three sessions of each year used Stimulus Set 1, and the last session used Stimulus Set 2 to investigate transfer effects. Each session consisted of alternating learning and test phases in a modified artificial grammar learning task. In Year 1, 7-year-olds and adults learned the regularities and showed transfer to Stimulus Set 2. Both groups retained their final performance level over the 1-year period. In Year 2, children and adults continued to improve with Stimulus Set 1 but did not show additional transfer gains. Adults overall outperformed children, but transfer effects were indistinguishable between both groups. The current results suggest that long-term memory traces are formed from repeated sequence learning that can be used to generalize sequence rules to new visual input. However, the current study did not provide evidence for a childhood advantage in learning and remembering sequence rules.

Developmental changes in the visual, haptic, and bimodal perception of geometric angles.

Geometrical knowledge is typically taught to children through a combination of vision and repetitive drawing (i.e. haptics), yet our understanding of how different spatial senses contribute to geometric perception during childhood is poor. Studies of line orientation suggest a dominant role of vision affecting the calibration of haptics during development; however, the associated multisensory interactions underpinning angle perception are unknown. Here we examined visual, haptic, and bimodal perception of angles across three age groups of children: 6 to 8 years, 8 to 10 years, and 10 to 12 years, with age categories also representing their class (grade) in primary school. All participants first learned an angular shape, presented dynamically, in one of three sensory tracing conditions: visual only, haptic only, or bimodal exploration. At test, which was visual only, participants selected a target angle from four possible alternatives with distractor angle sizes varying relative to the target angle size. We found a clear improvement in accuracy of angle perception with development for all learning modalities. Angle perception in the youngest group was equally poor (but above chance) for all modalities; however, for the two older child groups, visual learning was better than haptics. Haptic perception did not improve to the level of vision with age (even in a comparison adult group), and we found no specific benefit for bimodal learning over visual learning in any age group, including adults. Our results support a developmental increment in both spatial accuracy and precision in all modalities, which was greater in vision than in haptics, and are consistent with previous accounts of cross-sensory calibration in the perception of geometric forms.

Asymmetric stimulus representations bias visual perceptual learning.

The primate visual cortex contains various regions that exhibit specialization for different stimulus properties, such as motion, shape, and color. Within each region, there is often further specialization, such that particular stimulus features, such as horizontal and vertical orientations, are over-represented. These asymmetries are associated with well-known perceptual biases, but little is known about how they influence visual learning. Most theories would predict that learning is optimal, in the sense that it is unaffected by these asymmetries. However, other approaches to learning would result in specific patterns of perceptual biases. To distinguish between these possibilities, we trained human observers to discriminate between expanding and contracting motion patterns, which have a highly asymmetrical representation in the visual cortex. Observers exhibited biased percepts of these stimuli, and these biases were affected by training in ways that were often suboptimal. We simulated different neural network models and found that a learning rule that involved only adjustments to decision criteria, rather than connection weights, could account for our data. These results suggest that cortical asymmetries influence visual perception and that human observers often rely on suboptimal strategies for learning.

Current Developments in the Management of Amblyopia with the Use of Perceptual Learning Techniques.

Background and Objectives: Amblyopia is a neurodevelopmental disorder caused by interocular suppression of visual input, affecting visual acuity, stereopsis, contrast sensitivity, and other visual functions. Conventional treatment comprises occlusion of the sound eye. In recent years, novel therapies that deploy perceptual learning (PL) principles have been introduced. The purpose of this study is to assess the latest scientific data on this topic. Materials and Methods: For this purpose, we conducted a literature search for relevant studies published during the previous 4 years (2020-2023). Results: A plethora of visual perceptual learning protocols have been recently developed. Dichoptic video games, contrast rebalanced movies, and online perceptual training platforms are the main formats. Perceptual learning activates neuroplasticity, overcomes interocular suppression, and improves the visual impairments induced by amblyopia. Conclusions: This novel treatment is effective in both children and adults, as well as in patients non-responding to patching.

Contribution of statistical learning in learning to read across languages.

Statistical Learning (SL) refers to human's ability to detect regularities from environment Kirkham, N. Z. (2002) & Saffran, J. R. (1996). There has been a growing interest in understanding how sensitivity to statistical regularities influences learning to read. The current study systematically examined whether and how non-linguistic SL, Chinese SL, and English SL contribute to Chinese and English word reading among native Chinese-speaking 4th, 6th and 8th graders who learn English as a second language (L2). Children showed above-chance learning across all SL tasks and across all grades. In addition, developmental improvements were shown across at least two of the three grade ranges on all SL tasks. In terms of the contribution of SL to reading, non-linguistic auditory SL (ASL), English visual SL (VSL), and Chinese ASL accounted for a significant amount of variance in English L2 word reading. Non-linguistic ASL, Chinese VSL, English VSL, and English ASL accounted for a significant amount of variance in Chinese word reading. Our results provide clear and novel evidence for cross-linguistic contribution from Chinese SL to English reading, and from English SL to Chinese reading, highlighting a bi-directional relationship between SL in one language and reading in another language.

Does bilingual experience influence statistical language learning?

Statistical language learning (SL) tasks measure different aspects of foreign language learning. Studies have used SL tasks to investigate whether bilingual experience confers advantages in acquiring additional languages through implicit processes. However, the results have been inconsistent, which may be related to bilingualism-related features (e.g., degree of dissimilarity between the specific language pair) and other variables such as specific processes that are targeted by the SL task. In the present study, we compared the performance of one Spanish monolingual and two bilingual (Spanish-Basque and Spanish-English) groups across three well-established SL tasks. Each task targeted a different aspect of foreign language learning; specifically, word segmentation, morphological rule generalization, and word-referent learning. In Experiment 1, we manipulated sub-lexical phonotactic patterns to vary the difficulty of three SL tasks, with the results showing no differences between the groups in word segmentation. In Experiment 2, we included non-adjacent dependencies to target affixal morphology rule learning, but again no group-related differences were found. In Experiment 3, we addressed word learning using an audio-visual SL task combining exclusive and multiple word-referent mappings, and found that bilinguals outperformed monolinguals, suggesting that bilingualism may exert influences on SL at the lexical level. This advantage might have been mediated by the high working memory demands required to perform the task. Summarizing, this study shows no evidence for a general bilingual advantage in SL, although bilinguals may outperform monolinguals under specific experimental conditions such as SL tasks that place high demands on working memory processes. In addition, the similar performance of Spanish-Basque and Spanish-English bilinguals across all three SL tasks suggests that the degree of dissimilarity between pairs of spoken languages does not modulate SL skills.

Barnes maze test for spatial memory: A new, sensitive scoring system for mouse search strategies.

The Barnes maze is a task used to assess spatial learning and memory in rodents. It requires animals to learn the position of a hole that can be used as an escape from a bright and open arena. The often-used parameters of latency and path length to measure learning and memory do not reflect the different navigation strategies chosen by the animals. Here, we propose an 11-point scoring scheme to classify the search strategies developed by the animals during the initial training as well as after the change of the escape target to a new position. Strategy scores add an important dimension to time and path length to assess the behavior in this popular maze.

Quaternion Cross-Modality Spatial Learning for Multi-Modal Medical Image Segmentation.

Recently, the Deep Neural Networks (DNNs) have had a large impact on imaging process including medical image segmentation, and the real-valued convolution of DNN has been extensively utilized in multi-modal medical image segmentation to accurately segment lesions via learning data information. However, the weighted summation operation in such convolution limits the ability to maintain spatial dependence that is crucial for identifying different lesion distributions. In this paper, we propose a novel Quaternion Cross-modality Spatial Learning (Q-CSL) which explores the spatial information while considering the linkage between multi-modal images. Specifically, we introduce to quaternion to represent data and coordinates that contain spatial information. Additionally, we propose Quaternion Spatial-association Convolution to learn the spatial information. Subsequently, the proposed De-level Quaternion Cross-modality Fusion (De-QCF) module excavates inner space features and fuses cross-modality spatial dependency. Our experimental results demonstrate that our approach compared to the competitive methods perform well with only 0.01061 M parameters and 9.95G FLOPs.

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.

Teaching Zebrafish Development in a STEM-Based Science Camp for Middle School Students.

Zebrafish have been used as an education tool for students of all ages and can be used in many learning environments to teach different fields of science. In this study, we focus on the biology of zebrafish. We describe an educational program within a weeklong science camp for students between 12 and 14 years old. The methodology described is based on running annual science camps over an 11-year period. In these camps, students learnt about the developmental stages of zebrafish, as well as general zebrafish biology, husbandry, ecology, behavior, and reproduction. This article describes how to provide students and educators with an educational program to explore, discover, and contribute to the ever-evolving landscape of biological understanding through active and visual learning. We describe the methodology, the evaluation, revisions to our program over time, and future directions for expansion.

The role of intraamygdaloid oxytocin in spatial learning and avoidance learning.

The goal of the present study is to investigate the role of intraamygdaloid oxytocin in learning-related mechanisms. Oxytocin is a neuropeptide which is involved in social bonding, trust, emotional responses and various social behaviors. By conducting passive avoidance and Morris water maze tests on male Wistar rats, the role of intraamygdaloid oxytocin in memory performance and learning was investigated. Oxytocin doses of 10 ng and 100 ng were injected into the central nucleus of the amygdala. Our results showed that 10 ng oxytocin significantly reduced the time required to locate the platform during the Morris water maze test while significantly increasing the latency time in the passive avoidance test. However, the 100 ng oxytocin experiment failed to produce a significant effect in either of the tests. Wistar rats pretreated with 20 ng oxytocin receptor antagonist (L-2540) were administered 10 ng of oxytocin into the central nucleus of the amygdala and were also subjected to the aforementioned tests to highlight the role of oxytocin receptors in spatial- and avoidance learning. Results suggest that oxytocin supports memory processing during both the passive avoidance and the Morris water maze tests. Oxytocin antagonists can however block the effects of oxytocin in both tests. The results substantiate that oxytocin uses oxytocin receptors to enhance memory and learning performance.

Spatial transfer of object-based statistical learning.

A large number of recent studies have demonstrated that efficient attentional selection depends to a large extent on the ability to extract regularities present in the environment. Through statistical learning, attentional selection is facilitated by directing attention to locations in space that were relevant in the past while suppressing locations that previously were distracting. The current study shows that we are not only able to learn to prioritize locations in space but also locations within objects independent of space. Participants learned that within a specific object, particular locations within the object were more likely to contain relevant information than other locations. The current results show that this learned prioritization was bound to the object as the learned bias to prioritize a specific location within the object stayed in place even when the object moved to a completely different location in space. We conclude that in addition to spatial attention prioritization of locations in space, it is also possible to learn to prioritize relevant locations within specific objects. The current findings have implications for the inferred spatial priority map of attentional weights as this map cannot be strictly retinotopically organized.