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Aging and Alzheimer's disease are associated with chronic elevations in neuronal calcium influx via L-type calcium channels. The hippocampus, a primary memory encoding structure in the brain, is more vulnerable to calcium dysregulation in Alzheimer's disease. Recent research has suggested a link between L-type calcium channels and tau hyperphosphorylation. However, the precise mechanism of L-type calcium channel-mediated tau toxicity is not understood. In this study, we seeded a human tau pseudophosphorylated at 14 amino acid sites in rat hippocampal cornu ammonis 1 region to mimic soluble pretangle tau. Impaired spatial learning was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats as early as 1-3 months and worsened at 9-10 months post-infusion. Rats infused with wild-type human tau exhibited milder behavioural deficiency only at 9-10 months post-infusion. No tangles or plaques were observed in all time points examined in both human tau pseudophosphorylated at 14 amino acid sites and human tau-infused brains. However, human tau pseudophosphorylated at 14 amino acid sites-infused hippocampus exhibited a higher amount of tau phosphorylation at S262 and S356 than the human tau-infused rats at 3 months post-infusion, paralleling the behavioural deficiency observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Neuroinflammation indexed by increased Iba1 in the cornu ammonis 1 was observed in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 but not 9 months post-infusion. Spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats at 1-3 months post-infusion was paralleled by decreased neuronal excitability, impaired NMDA receptor-dependent long-term potentiation and augmented L-type calcium channel-dependent long-term potentiation at the cornu ammonis 1 synapses. L-type calcium channel expression was elevated in the soma of the cornu ammonis 1 neurons in human tau pseudophosphorylated at 14 amino acid sites-infused rats. Chronic L-type calcium channel blockade with nimodipine injections for 6 weeks normalized neuronal excitability and synaptic plasticity and rescued spatial learning deficiency in human tau pseudophosphorylated at 14 amino acid sites-infused rats. The early onset of L-type calcium channel-mediated pretangle tau pathology and rectification by nimodipine in our model have significant implications for preclinical Alzheimer's disease prevention and intervention.

The use of different mazes to assess spatial learning has become more common in fish behavior studies in recent decades. This increase in fish cognition research has opened the door to numerous possibilities for exciting and diverse questions, such as identifying ecological drivers of spatial cognition and understanding the role individual variation plays in navigational abilities. There are many different types of mazes, each with its own specific considerations, making it challenging to determine exactly which spatial test is the most relevant and appropriate for a particular experiment. Many spatial mazes, such as the T‐maze and Y‐maze, have been successfully adapted from rodent studies, particularly with respect to zebrafish, a widely accepted non‐mammalian model in biomedical studies. Standardization across studies is increasing with these easily accessible maze designs, validating them for use in fish; however, variations in design (e.g., length of arms and scale) and procedure still exist, and the impact of these variations on results is largely unknown. The efforts to standardize mazes outside zebrafish work are also more limited. Other mazes have been developed specifically for use on fish, with design modifications varying widely, making it difficult to draw comparisons. In this review, we have highlighted the many design and procedural elements that should be considered for the acquisition of reliable behavioral data, with the goal of drawing readers' attention to aspects of experimentation that are often not given the careful consideration that they deserve. We then argue that additional focused research and reporting is needed to produce more reliable methods in spatial learning research across a broader range of subjects. [ABSTRACT FROM AUTHOR]

Introduction: The vestibular system’s contribution to spatial learning and memory abilities may be clarified using the virtual Morris Water Maze Task (vMWMT). This is important because of the connections between the vestibular system and the hippocampus area. However, there is ongoing debate over the role of the vestibular system in developing spatial abilities. This study aimed to evaluate the relationship between Dynamic Visual Acuity (DVA) across three planes and spatial abilities. Methods: This cross-sectional study was conducted with 50 healthy adults aged 18 to 55 with normal stress levels and mental health and no neurological, audiological, or vestibular complaints. The Trail-Making Test (TMT) Forms A and B for the assessment of executive functions, the DVA test battery for the evaluation of visual motor functions, and the Virtual Morris Water Maze Test (vMWMT) for the assessment of spatial learning and spatial memory were performed. All participants also underwent the Benton Face Recognition Test (BFRT) and Digit Symbol Substitution Tests (DSST) to assess their relation with spatial memory. Results: DVA values in horizontal (H-DVA), vertical (V-DVA), and sagittal (S-DVA) planes ranged from (−0.26) to 0.36 logMAR, (−0.20) to 0.36 logMAR, and (−0.28) to 0.33 logMAR, respectively. The latency of three planes of DVA was affected by vMWMT (Horizontal, Vertical, and Sagittal; Estimate: 22.733, 18.787, 13.341, respectively p < 0.001). Moreover, a moderately significant correlation was also found, with a value of 0.571 between the Virtual MWM test and BFRT and a value of 0.539 between the DSST (p < 0.001). Conclusion: Spatial abilities in healthy adults were significantly influenced by dynamic visual functions across horizontal, vertical, and sagittal planes. These findings are expected to trigger essential discussions about the mechanisms that connect the vestibular-visual system to the hippocampus. The original vMWMT protocol is likely to serve as a model for future studies utilizing this technology. [ABSTRACT FROM AUTHOR]

This study analyses behavioural adaptations in a recently discovered European cave fish. Navigation in standardized labyrinth conditions was compared between this cave fish, its epigean ancestor, the European stone loach, Barbatula barbatula , and hybrid specimens. Loach behaviour was tracked and recorded using an infrared camera. In open field tests, in both dark and light conditions, cave loaches showed reduced thigmotaxis compared to the other two groups. Hybrid loaches generally showed strong avoidance of the open field, whereas epigean loaches avoided the open field more in light than in dark conditions. Other tests were performed in darkness only. Cave loaches showed more consistent lateralization in turning behaviour during exploration of the Y-maze than the other two groups, indicating a search strategy optimized for nonvisual navigation. In all groups, complex maze learning was evident in the first half of the 15 trials, with a reduction in latency of departure from the starting chamber, and in both time and track length to reach the food chamber. However, cave loaches were far more successful in finding food than were epigean loaches and hybrid loaches. When the path to the food chamber was altered, epigean loaches generally responded by changing their route, whereas cave loaches tended to continue following a previously learned path and hybrid loaches exhibited intermediate behaviours. In conclusion, the enhanced ability of cave loaches to navigating labyrinths in the dark compared to their epigean ancestor suggests the evolution of behavioural traits that optimize survival in caves. • Cave loaches showed less open field avoidance in darkness than epigean loaches. • Cave loaches showed most consistent lateralization of exploration in Y-maze test. • Cave loaches achieved greatest foraging success in darkness in complex maze. • In darkness, epigean loaches were least able to learn a complex pattern to navigate. • Hybrids' behaviours in darkness were often not intermediate of cave × epigean fish. [ABSTRACT FROM AUTHOR]

Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here. [ABSTRACT FROM AUTHOR]

Background: The authors had previously developed AnaVu, a low-resource 3D visualization tool for stereoscopic/monoscopic projection of 3D models generated from pre-segmented MRI neuroimaging data. However, its utility in neuroanatomical education compared to conventional methods (specifically whether the stereoscopic or monoscopic mode is more effective) is still unclear. Methods: A three-limb randomized controlled trial was designed. A sample (n = 152) from the 2022 cohort of MBBS students at Government Medical College, Thiruvananthapuram (GMCT), was randomly selected from those who gave informed consent. After a one-hour introductory lecture on brainstem anatomy and a dissection session, students were randomized to three groups (S – Stereo; M – Mono and C – Control). S was given a 20-min demonstration on the brainstem lesson module in AnaVu in stereoscopic mode. M was given the same demonstration, but in monoscopic mode. The C group was taught using white-board drawn diagrams. Pre-intervention and post-intervention tests for four domains (basic recall, analytical, radiological anatomy and diagram-based questions) were conducted before and after the intervention. Cognitive loads were measured using a pre-validated tool. The groups were then swapped -S→ M, M →S and C→S, and they were asked to compare the modes. Results: For basic recall questions, there was a statistically significant increase in the pre/post-intervention score difference of the S group when compared to the M group [p = 0.03; post hoc analysis, Bonferroni corrections applied] and the C group [p = 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. For radiological anatomy questions, the difference was significantly higher for S compared to C [p < 0.001; ANOVA test; post hoc analysis, Bonferroni corrections applied]. Cognitive load scores showed increased mean germane load for S (33.28 ± 5.35) and M (32.80 ± 7.91) compared with C (28.18 ± 8.17). Subjective feedbacks showed general advantage for S and M compared to C. Out of the S and M swap cohorts, 79/102 preferred S, 13/102 preferred M, and 6/102 preferred both. Conclusions: AnaVu tool seems to be effective for learning neuroanatomy. The specific advantage seen when taught with stereoscopy in basic recall and radiological anatomy learning shows the importance of how visualization mode influences neuroanatomy learning. Since both S and M are preferred in subjective feedbacks, these results have implications in choosing methods (stereoscopic – needs 3D projectors; monoscopic – needs web based or hand-held devices) to scale AnaVu for anatomy teaching in medical colleges in India. Since stereoscopic projection is technically novel and cost considerations are slightly higher compared to monoscopic projection, the specific advantages and disadvantages of each are relevant in the Indian medical education scenario. [ABSTRACT FROM AUTHOR]

Reliance on digital navigation aids has already shown negative impacts on navigators' innate spatial abilities. How this happens is still an open research question. We report on an empirical study with twenty-four experienced (male) taxi drivers to evaluate the long-term impacts of in-car navigation system use on the spatial learning ability of these navigation experts. Specifically, we measured cognitive load by means of electroencephalography (EEG) coupled with eye tracking to assess their visuospatial attention allocation during a video-based route-following task while driving through an unknown urban environment. We found that long-term reliance on in-car navigation aids did not affect participants' visual attention allocation during spatial learning but rather limited their ability to encode viewed geographic information into memory, which, in turn, led to greater cognitive load, especially along route segments between intersections. Participants with greater dependence on in-car navigation aids performed worse on the spatial knowledge tests. Our combined behavioral and neuropsychological findings provide evidence for the impairment of expert navigators' spatial learning ability when exposed to long-term use of digital in-car navigation aids. [ABSTRACT FROM AUTHOR]

Cognitive abilities are crucial for survival and adaptation, enabling animals to navigate their environment, recognize predators and remember the location of food resources. However, underlying factors related to learning and memory can be energetically demanding and thus may vary depending on an individual's metabolism or aerobic capacity, potentially affecting individuals' cognitive performance. In this study, we explored the link between cognitive performance and whole-body metabolic traits, including aerobic scope (AS), maximum metabolic rate (MMR) and standard metabolic rate (SMR). European minnows, Phoxinus phoxinus , were trained over 20 days to locate a food reward in a maze. Individuals were trained in either a simple (two-door) or a complex (four-door) maze. Fish in the simpler maze had consistently higher success and a lower latency to reach the reward, suggesting the two-door maze was less cognitively challenging. We found a correlation between metabolic traits and cognitive performance traits (i.e. success and latency to reach the reward) at the end of training. However, this relationship varied depending on maze complexity. In the two-door maze, individuals with higher MMR and SMR had higher success and a lower latency to reach the reward. However, in the more complex maze, fish with lower metabolic rates (MMR and SMR) had higher success and lower latency to reach the reward. AS followed similar patterns but mostly affected the success to reach the reward. In simpler environments, having a higher metabolism may be more beneficial for cognitive performance, whereas in complex environments, having a lower metabolism may be more beneficial as it could be associated with a slower but more thorough exploration and learning process. • Fish in two-door mazes had higher success and lower latency to reach a reward. • Fish with higher metabolic rates (MMR, SMR) performed better in two-door mazes. • Fish with lower MMR and SMR performed better in four-door mazes. • Aerobic scope followed similar patterns but mostly affected success to reach a reward. • Metabolic traits and cognitive performance were correlated at the end of training. [ABSTRACT FROM AUTHOR]

Objective; Oxidative stress results in neuronal degeneration leading to cognitive decline. Microglia in brain tissue produces reactive oxygen species (ROS), which modulate synaptic communication between neurons. ROS can lead to neuroinflammation, which can cause neurodegeneration and memory loss. Talinum triangulare was investigated for its cognitive, anti-oxidative and anti-inflammatory potentials in male wistar rats. Materials and methods; 25 adult female rats weighing between 150 g–200 g were grouped (n = 5) into Group 1 (control group) received 1 mL/kg of distilled water, group 2–5 were administered with 100 mg/kg, 200 mg/kg and 400 mg/kg T. triangulare methanol extract and 2.5 mg/kg donepezil, 100 mg/kg cadmium respectively via oral gavage. The administration lasted for 21 days and neuro behavioural parameters, biochemical and histological analysis of the hippocampus were evaluated. The assessment of spatial learning and memory was evaluated using Classic labyrinth task. Results; There was significantly (p < 0.05) reduced escape time latency and increased time latency in the probe trial in Morris water maze; and reduced time latency in the labyrinth by T. triangulare methanol extract (100, 200 and 400 mg/kg) compared with the control and cadmium treated groups. T. triangulare methanol extract and donepezil significantly (p < 0.05) reduced acetylcholinesterase (AChE), tissue necrosis factor-α (TNF-α), interleukin-6 (IL-6) activities and significantly (p < 0.05) increased gluthathione peroxidase activity (GPx) and catalase (CAT) respectively. Conclusion; These findings revealed that T. triangulare methanol extract enhanced cognitive function and exhibited anti-oxidative and anti-inflammatory potentials. [ABSTRACT FROM AUTHOR]

How the development and function of neural circuits governing learning and memory are affected by insults in early life remains poorly understood. The goal of this study was to identify putative changes in cortico-hippocampal signaling mechanisms that could lead to learning and memory deficits in a clinically relevant developmental pathophysiological rodent model, Febrile status epilepticus (FSE). FSE in both pediatric cases and the experimental animal model, is associated with enduring physiological alterations of the hippocampal circuit and cognitive impairment. Here, we deconstruct hippocampal circuit throughput by inducing slow theta oscillations in rats under urethane anesthesia and isolating the dendritic compartments of CA1 and dentate gyrus subfields, their reception of medial and lateral entorhinal cortex inputs, and the efficacy of signal propagation to each somatic cell layer. We identify FSE-induced theta-gamma decoupling at cortical synaptic input pathways and altered signal phase coherence along the CA1 and dentate gyrus somatodendritic axes. Moreover, increased DG synaptic activity levels are predictive of poor cognitive outcomes. We propose that these alterations in cortico-hippocampal coordination interfere with the ability of hippocampal dendrites to receive, decode and propagate neocortical inputs. If this frequency-specific syntax is necessary for cortico-hippocampal coordination and spatial learning and memory, its loss could be a mechanism for FSE cognitive comorbidities.

Structural differences along the hippocampal long axis are believed to underlie meaningful functional differences. Yet, recent datadriven 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. [ABSTRACT FROM AUTHOR]

Duchenne muscular dystrophy is a severe neuromuscular disorder that is caused by mutations in the DMD gene, resulting in a disruption of dystrophin production. Next to dystrophin expression in the muscle, different isoforms of the protein are also expressed in the brain and lack of these isoforms leads to cognitive and behavioral deficits in patients. It remains unclear how the loss of the shorter dystrophin isoform Dp140 affects these processes. Using a variety of behavioral tests, we found that mdx and mdx4cv mice (which lack Dp427 or Dp427 + Dp140, respectively) exhibit similar deficits in working memory, movement patterns and blood–brain barrier integrity. Neither model showed deficits in spatial learning and memory, learning flexibility, anxiety or spontaneous behavior, nor did we observe differences in aquaporin 4 and glial fibrillary acidic protein. These results indicate that in contrast to Dp427, Dp140 does not play a crucial role in processes of learning, memory and spontaneous behavior. [ABSTRACT FROM AUTHOR]

Previous studies have shown that whip spiders (Amblypygi) can use a variety of cues to navigate to and recognize a home refuge. The current study aimed to determine whether whip spiders were capable of using the boundary geometry of an experimental space (geometric information) to guide goal-directed navigation and to investigate any preferential use of geometric or feature (visual) information. Animals were first trained to find a goal location situated in one corner of a rectangular arena (geometric information) fronting a dark-green-colored wall, which created a brightness contrast with the other three white walls (feature information). Various probe trials were then implemented to determine cue use. It was found that animals were capable of directing their choice behavior towards geometrically correct corners at a rate significantly higher than chance, even when the feature cue was removed. By contrast, choice behavior dropped to random chance when geometric information was removed (test in a square arena) and only feature information remained. Choice behavior was also reduced to chance when geometric and feature information were set in conflict (by moving the feature cue to one of the longer walls in the rectangular arena). The data thus suggest that whip spiders are capable of using geometric information to guide goal-directed navigation and that geometric information is preferred over feature guidance, although a feature cue may set the context for activating geometry-guided navigation. Experimental design limitations and future directions are discussed. [ABSTRACT FROM AUTHOR]

Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals’ brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributesto the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function. [ABSTRACT FROM AUTHOR]

Literature reported mixed evidence on whether active exploration benefits spatial knowledge acquisition over passive exploration. Active spatial learning typically involves at least physical control of one's movement or navigation decision-making, while passive participants merely observe during exploration. To quantify the effects of active exploration in learning large-scale, unfamiliar environments, we analysed previous findings with the multi-level meta-analytical model. Potential moderators were identified and examined for their contributions to the variability in effect sizes. Of the 128 effect sizes retrieved from 33 experiments, we observed a small to moderate advantage of active exploration over passive observation. Important moderators include gender composition, decision-making, types of spatial knowledge, and matched visual information. We discussed the implications of the results along with the limitations. [ABSTRACT FROM AUTHOR]

Spatial learning, memory, and reactivity of the hypothalamic—pituitary—adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny. [ABSTRACT FROM AUTHOR]

Perceptual learning, the improvement of perceptual judgments with practice, occurs in many visual tasks. There are, however, relatively fewer studies examining perceptual learning in spatial frequency judgments. In addition, perceptual learning has generally been studied in two-alternative tasks, occasionally in n-alternative tasks, and infrequently in identification. Recently, perceptual learning was found in an orientation identification task (eight-alternatives) and was well accounted for by a new identification integrated reweighting theory (I-IRT) (Liu et al., submitted). Here, we examined perceptual learning in a similar eight-alternative spatial frequency absolute identification task in two different training protocols, finding learning in the majority but not all observers. We fit the I-IRT to the spatial frequency learning data and discuss possible model explanations for variations in learning.

Although sex differences in learning behaviors are well documented, sexual dimorphism in the synaptic processes of encoding is only recently appreciated. Studies in male rodents have built upon the discovery of long-term potentiation (LTP), and acceptance of this activity-dependent increase in synaptic strength as a mechanism of encoding, to identify synaptic receptors and signaling activities that coordinate the activity-dependent remodeling of the subsynaptic actin cytoskeleton that is critical for enduring potentiation and memory. These molecular substrates together with other features of LTP, as characterized in males, have provided an explanation for a range of memory phenomena including multiple stages of consolidation, the efficacy of spaced training, and the location of engrams at the level of individual synapses. In the present report, we summarize these findings and describe more recent results from our laboratories showing that in females the same actin regulatory mechanisms are required for hippocampal LTP and memory but, in females only, the engagement of both modulatory receptors such as TrkB and synaptic signaling intermediaries including Src and ERK1/2 requires neuron-derived estrogen and signaling through membrane-associated estrogen receptor α (ERα). Moreover, in association with the additional ERα involvement, females exhibit a higher threshold for hippocampal LTP and spatial learning. We propose that the distinct LTP threshold in females contributes to as yet unappreciated sex differences in information processing and features of learning and memory.

IntroductionThe vestibular system’s contribution to spatial learning and memory abilities may be clarified using the virtual Morris Water Maze Task (vMWMT). This is important because of the connections between the vestibular system and the hippocampus area. However, there is ongoing debate over the role of the vestibular system in developing spatial abilities. This study aimed to evaluate the relationship between Dynamic Visual Acuity (DVA) across three planes and spatial abilities.MethodsThis cross-sectional study was conducted with 50 healthy adults aged 18 to 55 with normal stress levels and mental health and no neurological, audiological, or vestibular complaints. The Trail-Making Test (TMT) Forms A and B for the assessment of executive functions, the DVA test battery for the evaluation of visual motor functions, and the Virtual Morris Water Maze Test (vMWMT) for the assessment of spatial learning and spatial memory were performed. All participants also underwent the Benton Face Recognition Test (BFRT) and Digit Symbol Substitution Tests (DSST) to assess their relation with spatial memory.ResultsDVA values in horizontal (H-DVA), vertical (V-DVA), and sagittal (S-DVA) planes ranged from (−0.26) to 0.36 logMAR, (−0.20) to 0.36 logMAR, and (−0.28) to 0.33 logMAR, respectively. The latency of three planes of DVA was affected by vMWMT (Horizontal, Vertical, and Sagittal; Estimate: 22.733, 18.787, 13.341, respectively p < 0.001). Moreover, a moderately significant correlation was also found, with a value of 0.571 between the Virtual MWM test and BFRT and a value of 0.539 between the DSST (p < 0.001).ConclusionSpatial abilities in healthy adults were significantly influenced by dynamic visual functions across horizontal, vertical, and sagittal planes. These findings are expected to trigger essential discussions about the mechanisms that connect the vestibular-visual system to the hippocampus. The original vMWMT protocol is likely to serve as a model for future studies utilizing this technology.

ABSTRACTMixed reality technology has been increasingly used for navigation. While most MR-based navigation systems are currently based on hand-held devices, for example, smartphones, head-mounted MR devices have become more and more popular in navigation. Much research has been conducted to investigate the navigation experience in MR. However, it is still unclear how ordinary users react to the first-person view and FOV (field of view)-limited navigation experience, especially in terms of spatial learning. In our study, we investigate how visualization in MR navigation affects spatial learning. More specifically, we test two related hypotheses: incorrect virtual information can lead users into incorrect spatial learning, and the visualization style of direction can influence users’ spatial learning and experience. We designed a user interface in Microsoft HoloLens 2 and conducted a user study with 40 participants. The user study consists of a walking session in which users wear Microsoft HoloLens 2 to navigate to an unknown destination, pre- and post-walking questionnaires, sketch map drawing, and a semi-structured interview about the user interface design. The results provide preliminary confirmation that users’ spatial learning can be misled by incorrect information, even in a small study area, but this misleading effect can be compensated by considerate visualization, for example, including lines instead of using only arrows as direction indicators. Arrows with or without lines as two visualization alternatives also influenced the user’s spatial learning and evaluation of the designed elements. Besides, the study shows that users’ preferences for navigation interfaces are diverse, and an adaptable interface should be provided. The results contribute to the design of head-mounted MR-based navigation interfaces and the application of MR in navigation in general.

Dendrites of hippocampal CA1 pyramidal cells amplify clustered glutamatergic input by activation of voltage-gated sodium channels and N-methyl-D-aspartate receptors (NMDARs). NMDAR activity depends on the presence of NMDAR co-agonists such as D-serine, but how co-agonists influence dendritic integration is not well understood. Using combinations of whole-cell patch clamp, iontophoretic glutamate application, two-photon excitation fluorescence microscopy and glutamate uncaging in acute rat and mouse brain slices we found that exogenous D-serine reduced the threshold of dendritic spikes and increased their amplitude. Triggering an astrocytic mechanism controlling endogenous D-serine supply via endocannabinoid receptors (CBRs) also increased dendritic spiking. Unexpectedly, this pathway was activated by pyramidal cell activity primarily in the theta range, which required HCN channels and astrocytic CB1Rs. Therefore, astrocytes close a positive and frequency-dependent feedback loop between pyramidal cell activity and their integration of dendritic input. Its disruption in mice led to an impairment of spatial memory, which demonstrated its behavioral relevance.

Background: Caloric restriction (CR) has been recognized for its benefits in delaying age-related diseases and extending lifespan. While its effects on amyloid pathology in Alzheimer's disease (AD) mouse models are well-documented, its effects on tauopathy, another hallmark of AD, are less explored. Objective: To assess the impact of a short-term 30% CR regimen on age-dependent spatial learning deficits and pathological features in a tauopathy mouse model. Methods: We subjected male PS19 tau P301S (hereafter PS19) and age-matched wildtype mice from two age cohorts (4.5 and 7.5 months old) to a 6-week 30% CR regimen. Spatial learning performance was assessed using the Barnes Maze test. Tau pathology, neuroinflammation, hippocampal cell proliferation, and neurogenesis were evaluated in the older cohort by immunohistochemical staining and RT-qPCR. Results: CR mitigated age-dependent spatial learning deficits in PS19 mice but exhibited limited effects on tau pathology and the associated neuroinflammation. Additionally, we found a decrease in hippocampal cell proliferation, predominantly of Iba1+ cells. Conclusions: Our findings reinforce the cognitive benefits conferred by CR despite its limited modulation of disease pathology. Given the pivotal role of microglia in tau-driven pathology, the observed reduction in Iba1+ cells under CR suggests potential therapeutic implications, particularly if CR would be introduced early in disease progression. [ABSTRACT FROM AUTHOR]

Hippocampal afferent inputs, terminating on proximal and distal subfields of the cornus ammonis (CA), enable the functional discrimination of 'what' (item identity) and 'where' (spatial location) elements of a spatial representation. This kind of information is supported by structures such as the retrosplenial cortex (RSC). Spatial content learning promotes the expression of hippocampal synaptic plasticity, particularly long-term depression (LTD). In the CA1 region, this is specifically facilitated by the learning of item-place features of a spatial environment. Gene-tagging, by means of time-locked fluorescence in situ hybridization (FISH) to detect nuclear expression of immediate early genes, can reveal neuronal populations that engage in experience-dependent information encoding. In the current study, using FISH, we examined if learning-facilitated LTD results in subfield-specific information encoding in the hippocampus and RSC. Rats engaged in novel exploration of small items during stimulation of Schaffer collateral-CA1 synapses. This resulted in LTD (> 24 h). FISH, to detect nuclear expression of Homer1a, revealed that the distal-CA1 and proximal-CA3 subcompartments were particularly activated by this event. By contrast, all elements of the proximodistal cornus ammonis-axis showed equal nuclear Homer1a expression following LTD induction solely by means of afferent stimulation. The RSC exhibited stronger nuclear Homer1a expression in response to learning-facilitated LTD, and to novel item-place experience, compared to LTD induced by sole afferent stimulation in CA1. These results show that both the cornus ammonis and RSC engage in differentiated information encoding of item-place learning that is salient enough, in its own right, to drive the expression of hippocampal LTD. These results also reveal a novel role of the RSC in item-place learning. [ABSTRACT FROM AUTHOR]

Phenotypic variation may influence social structure if animals associate nonrandomly based on phenotypic traits. For animals that rely on cognition for survival, variation in cognitive ability may also affect social structure. Individuals with worse cognitive abilities could benefit from preferentially associating with conspecifics with better cognition, from being more gregarious, or both, allowing them access to resources. Climatic conditions influence resource availability, which may also affect the relative benefits of assortment or gregariousness, resulting in spatiotemporal variation of social patterns. Using 5 years of data, we investigated assortment by spatial cognitive ability and associations between sociality and spatial cognition in food-caching mountain chickadees, Poecile gambeli, inhabiting harsher environments at higher elevations and milder environments at lower elevations. Elevation environments differ in overwinter severity and in the harshest winter, high elevation chickadees with better spatial learning and memory abilities were less gregarious and showed lower social differentiation (or choosiness) than those with worse spatial learning and memory abilities but did not assort based on these traits. In two other seasons, including the second harshest winter, high elevation chickadees that were less cognitively flexible showed more social differentiation than those that were more cognitively flexible. In these two seasons alone, chickadees negatively assorted by spatial learning and memory performance. Chickadees from low elevations only demonstrated negative assortment in the second harshest winter. All other results were nonsignificant, suggesting that overall, individual spatial cognitive abilities or those of their associates have little influence on social preferences. Significance statement: We showed that under certain environmental conditions, social behavior may be related to spatial cognitive abilities in mountain chickadees that rely heavily on spatial cognition for overwinter survival, but that overall, cognition does not appear to influence social behavior. In the few years that patterns were present, they fit three trends: 1) chickadees with worse spatial cognitive abilities were more gregarious; 2) chickadees with worse spatial cognitive abilities were choosier; and/or 3) chickadees had stronger associations with social partners that had spatial cognitive abilities that differed from their own and weaker associations with those of similar cognitive abilities. While it is unclear under which specific circumstances these patterns emerge, they coincided with extreme snowfall, suggesting that individuals with worse spatial cognition alter their social behavior to buffer against their relatively greater risk of starvation under extenuating circumstances. [ABSTRACT FROM AUTHOR]

Mixed reality technology has been increasingly used for navigation. While most MR-based navigation systems are currently based on hand-held devices, for example, smartphones, head-mounted MR devices have become more and more popular in navigation. Much research has been conducted to investigate the navigation experience in MR. However, it is still unclear how ordinary users react to the first-person view and FOV (field of view)-limited navigation experience, especially in terms of spatial learning. In our study, we investigate how visualization in MR navigation affects spatial learning. More specifically, we test two related hypotheses: incorrect virtual information can lead users into incorrect spatial learning, and the visualization style of direction can influence users' spatial learning and experience. We designed a user interface in Microsoft HoloLens 2 and conducted a user study with 40 participants. The user study consists of a walking session in which users wear Microsoft HoloLens 2 to navigate to an unknown destination, pre- and post-walking questionnaires, sketch map drawing, and a semi-structured interview about the user interface design. The results provide preliminary confirmation that users' spatial learning can be misled by incorrect information, even in a small study area, but this misleading effect can be compensated by considerate visualization, for example, including lines instead of using only arrows as direction indicators. Arrows with or without lines as two visualization alternatives also influenced the user's spatial learning and evaluation of the designed elements. Besides, the study shows that users' preferences for navigation interfaces are diverse, and an adaptable interface should be provided. The results contribute to the design of head-mounted MR-based navigation interfaces and the application of MR in navigation in general. [ABSTRACT FROM AUTHOR]

Objectives: Spatial cognition is a perceptual-motor function that pertains to the comprehension and processing of two-dimensional and three-dimensional space. The impairment of any sensory system can have adverse effects on cognitive functioning. The objective of this study is to examine spatial cognition in adults with hearing impairments. Methods: There were a total of 61 individuals in this study: thirty-six with hearing loss and 25 with normal hearing. The Spatial Orientation Test (SOT), the Mental Rotation test (MR), and the Money's Road Map Test (RMT) were administered to assess participants' spatial learning-orientation, mental imagery-rotation, and spatial navigation abilities. A high number of errors in RMT, high angle difference in SOT and a low score in MR suggest poor spatial abilities. Results: Participants with hearing loss had a greater number of RMT errors and SOT angle difference, but lower MR scores than those with normal hearing (P <.001). Hearing impairment negatively impacted all 3 spatial cognitive assessments. Hearing loss was associated with a 6.9 increase in the number of RMT errors (95% Confidence Interval (CI): 4.8, 9), a 23.6 increase in the SOT angle difference (95% CI: 16, 31.2), and an 8.5 decrease in the MR score (95% CI: −10.8, −6.2). Conclusions: The study found that individuals with hearing loss exhibited lower performance in various cognitive tasks related to spatial orientation, navigation, spatial learning, mental imagery, and rotation abilities when compared to an age and sex matched control group. In future study, it is imperative to place greater emphasis on hearing loss as a potential detrimental factor in the prediction of spatial cognition impairment. [ABSTRACT FROM AUTHOR]

Coercive mating is a sexual selection strategy that is likely to influence female cognition. Female harassment levels have been linked to altered brain gene expression patterns and brain size evolution, suggesting females may respond to coercive mating by investing energy into “outsmarting” males. However, females exposed to coercive males have decreased foraging efficiency and likely increased stress levels, suggesting their brain function might instead be impaired. While it is therefore likely that coercive mating impacts female cognitive abilities, a direct test of this idea is currently lacking. In this study, we investigate the impact of coercive mating on female spatial memory and cognitive flexibility in a species with prevalent coercive mating. We compared the performance of female porthole livebearers (Poeciliopsis gracilis), which had been previously housed alone or with a coercive male, in both a spatial food localization task and a reversal learning task. While we found that both single and paired fish exhibited high proficiency in learning both tasks, we found no differences in learning ability between females that had or had not experienced coercive mating. In addition, our study found that the presence of a coercive male had no impact on female fecundity, but did influence female mass and standard length. Several studies have assumed that the presence of males, particularly coercive males, may affect the cognitive performance of female fish. However, our study shows that for some species females adapted to coercive mating regimes may be unaffected by male presence with regards to some cognitive tasks. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) affects neurogenesis and spatial learning, and increases neuroinflammation after a pediatric mild traumatic brain injury (mTBI). Previous studies have shown that ELS has minimal effects in juveniles but shows age-dependent effects in adults. Hence, we aimed to evaluate the effects of ELS in adult male rats after an mTBI. Maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days was used as the ELS model. At P110, the rats were subjected to a mild controlled cortical impact injury (2.6 mm) or sham surgery. Spatial learning was evaluated in the Morris water maze (MWM) 14 days after surgery and both microglial activation and neurogenesis were quantified. The results indicate that MS180 + mTBI, but not control (CONT) + mTBI, rats show deficiencies in the acquisition of spatial learning. mTBI led to comparable increases in microglial activation in both the hilus and cortical regions for both groups. However, MS180 + mTBI rats exhibited a greater increase in microglial activation in the ipsilateral CA1 hippocampus subfield compared with CONT + mTBI. Interestingly, for the contralateral CA1 region, this effect was observed exclusively in MS180 + mTBI. ELS and mTBI independently caused a decrease in hippocampal neurogenesis and this effect was not increased further in MS180 + mTBI rats. The findings demonstrate that ELS and mTBI synergistically affect cognitive performance and neuroinflammation, thus supporting the hypothesis that increased inflammation resulting from the combination of ELS and mTBI could underlie the observed effects on learning. [ABSTRACT FROM AUTHOR]

Methamphetamine (MA) is a highly addictive drug, and MA use disorder is often comorbid with anxiety and cognitive impairment. These comorbid conditions are theorized to reflect glutamate-related neurotoxicity within the frontal cortical regions. However, our prior studies of MA-sensitized mice indicate that subchronic, behaviorally non-contingent MA treatment is sufficient to dysregulate glutamate transmission in mouse brain. Here, we extend this prior work to a mouse model of high-dose oral MA self-administration (0.8, 1.6, or 3.2 g/L; 1 h sessions × 7 days) and show that while female C57BL/6J mice consumed more MA than males, MA-experienced mice of both sexes exhibited some signs of anxiety-like behavior in a behavioral test battery, although not all effects were concentration-dependent. No MA effects were detected for our measures of visually cued spatial navigation, spatial learning, or memory in the Morris water maze; however, females with a history of 3.2 g/L MA exhibited reversal-learning deficits in this task, and mice with a history of 1.6 g/L MA committed more working-memory incorrect errors and relied upon a non-spatial navigation strategy during the radial-arm maze testing. Relative to naïve controls, MA-experienced mice exhibited several changes in the expression of certain glutamate receptor-related proteins and their downstream effectors within the ventral and dorsal areas of the prefrontal cortex, the hippocampus, and the amygdala, many of which were sex-selective. Systemic pretreatment with the mGlu1-negative allosteric modulator JNJ 162596858 reversed the anxiety-like behavior expressed by MA-experienced mice in the marble-burying test, while systemic pretreatment with NMDA or the NMDA antagonist MK-801 bi-directionally affected the MA-induced reversal-learning deficit. Taken together, these data indicate that a relatively brief history of oral MA is sufficient to induce some signs of anxiety-like behavior and cognitive dysfunction during early withdrawal that reflect, at least in part, MA-induced changes in the corticolimbic expression of certain glutamate receptor subtypes of potential relevance to treating symptoms of MA use disorder. [ABSTRACT FROM AUTHOR]

Over the last two decades, animal models have been used to evaluate the physiological and cognitive effects of mobile phone exposure. Here, we used a head-only exposure system in rats to determine whether exposure to 900 MHz GSM electromagnetic fields (EMFs) induces regional changes in neuronal activation as revealed by c-Fos imaging. In a first study, rats were exposed for 2 h to brain average specific absorption rates (BASARs) ranging from 0.5 to 6 W/kg. Changes in neuronal activation were found to be dose-dependent, with significant increases in c-Fos expression occurring at BASAR of 1 W/kg in prelimbic, infralimbic, frontal, and cingulate cortices. In a second study, rats were submitted to either a spatial working memory (WM) task in a radial maze or a spatial reference memory (RM) task in an open field arena. Exposures (45 min) were conducted before each daily training session (BASARs of 1 and 3.5 W/kg). Control groups included sham-exposed and control cage animals. In both tasks, behavioral performance evolved similarly in the four groups over testing days. However, c-Fos staining was significantly reduced in cortical areas (prelimbic, infralimbic, frontal, cingulate, and visual cortices) and in the hippocampus of animals engaged in the WM task (BASARs of 1 and 3.5 W/kg). In the RM task, EMF exposure-induced decreases were limited to temporal and visual cortices (BASAR of 1 W/kg). These results demonstrate that both acute and subchronic exposures to 900 MHz EMFs can produce region-specific changes in brain activity patterns, which are, however, insufficient to induce detectable cognitive deficits in the behavioral paradigms used here.

Introduction: This study aimed to investigate the potential neuroprotective effects of sodium hydrosulfide (NaHS) as an H2S donor on spatial learning and memory in the streptoztocin (STZ) rat model of Alzheimer’s disease. Methods: The animals were divided into the following groups: Control, NaHS (2.8 mg/kg per day), and Alzheimer's disease (AD) groups, which included STZ, STZ+saline, and STZ+NaHS. The last three groups consisted of Alzheimer's rats that were administered either saline or NaHS at doses of 2.8 and 5.6 mg/kg per day for a duration of 10 days. To induce AD, STZ at a dose of 3 mg/kg (10 μl per injection site) was administered into the lateral ventricles. All rats underwent training in the Morris water maze. Results: Our results showed that the intraventricular injection of STZ resulted in a significant increase in both the time taken and distance traveled to reach the platform compared to the control group. The memory deficits induced by STZ were mitigated by the administration of sodium hydrosulfide, leading to a decrease in the time and distance needed to reach the platform. Additionally, in the probe test, the percentage of time spent and distance traveled in the target quadrant was significantly higher in the group treated with sodium hydrosulfide group compared to the saline-treated STZ group. Conclusion: Sodium hydrosulfide was found to enhance learning and memory in AD rats. These findings indicate that sodium hydrosulfide treatment may be beneficial for addressing cognitive deficits in AD. [ABSTRACT FROM AUTHOR]

This preliminary study sought to examine stimulus control influences on navigation behaviors of adult human participants in a virtual simulation of a maze. The maze design was adapted from Morris's (Journal of Neuroscience Methods, 11, 47–60, 1984) "water maze" typically used with rats. In our study, in a "simple" condition, participants navigate the same open-field maze across a fixed number of trials until encountering a hidden platform to escape. In a "complex" condition, invisible walls are placed in the maze, constraining the participant's movements. Participants learned to rely more on distal cues in the simple condition compared to the complex condition, as measured by the percentage of viewing angles above a given threshold. The quantification of these observing responses provides an objective measurement towards delineating types of navigational strategies. [ABSTRACT FROM AUTHOR]

Functional asymmetries of the avian visual system can be studied in monocularly occluded birds, as their hemispheres are largely independent. Right and left monocularly occluded homing pigeons and control birds under binocular view have been trained in a food localisation task in an octagonal outdoor arena provided with one coloured beacon on each wall. The three groups were tested after the removal of the visual beacons, so to assess their sun compass learning abilities. Pigeons using the left eye/right hemisphere system exhibited slower learning compared to the other monocular group. During the test in the arena void of visual beacons, the three groups of birds, regardless of their visual condition, were generally able to identify the training sector by exclusively relying on sun compass information. However, the directional choices of the pigeons with the left eye/right hemisphere in use were significantly affected by the removal of the beacons, while both control pigeons and birds with the right eye/left hemisphere in use displayed unaltered performances during the test. A subsample of pigeons of each group were re-trained in the octagonal arena with visual beacons present and tested after the removal of visual beacons after a 6 h fast clock-shift treatment. All birds displayed the expected deflection consistent to the sun compass use. While birds using either the left or the right visual systems were equally able to learn a sun compass-mediated spatial task, the left eye/right hemisphere visual system displayed an advantage in relying on visual beacons. [ABSTRACT FROM AUTHOR]

There is evidence that cannabis use during adolescence leads to memory and cognitive problems in young adulthood but little is known about effects of early life cannabis exposure on synaptic operations that are critical for encoding and organizing information. We report here that a 14-day course of daily Δ9-tetrahydrocannabinol treatments administered to adolescent rats and mice (aTHC) leads to profound but selective deficits in synaptic plasticity in two axonal systems in female, and to lesser extent male, hippocampus as assessed in adulthood. Adolescent-THC exposure did not alter basic synaptic transmission (input/output curves) and had only modest effects on frequency facilitation. Nevertheless, aTHC severely impaired the endocannabinoid-dependent long-term potentiation in the lateral perforant path in females of both species, and in male mice; this was reliably associated with impaired acquisition of a component of episodic memory that depends on lateral perforant path function. Potentiation in the Schaffer-commissural (S-C) projection to field CA1 was disrupted by aTHC treatment in females only and this was associated with both a deficit in estrogen effects on S-C synaptic responses and impairments to CA1-dependent spatial (object location) memory. In all the results demonstrate sexually dimorphic and projection system-specific effects of aTHC exposure that could underlie discrete effects of early life cannabinoid usage on adult cognitive function. Moreover they suggest that some of the enduring, sexually dimorphic effects of cannabis use reflect changes in synaptic estrogen action.

ObjectiveFebrile seizures (FSs) are the most common form of seizures in children. Single short FSs are benign, but FSs lasting longer than 30 min, termed febrile status epilepticus, may result in neurological sequelae. However, there is little information about an intermediary condition, brief recurrent FSs (RFSs). The goal of this study was to determine the role of RFSs on spatial learning and memory and the properties of spontaneous hippocampal signals.MethodsA hippocampus-dependent active avoidance task was used to assess spatial learning and memory in adult rats that underwent experimental RFSs (eRFSs) in early life compared with their littermate controls. Following completion of the task, we utilized high-density laminar probes to measure spontaneous hippocampal CA1 circuit activity under urethane anesthesia, which allowed for the simultaneous recording of input regions in CA1 associated with both CA3 and entorhinal cortex.ResultsRFSs did not result in deficits in the active avoidance spatial test, a hippocampus-dependent test of spatial learning and memory. However, in vivo high-density laminar electrode recordings from eRFS rats had significantly altered power and frequency expression of theta and gamma bandwidths as well as signaling efficacy along the CA1 somatodendritic axis. Thus, although eRFS modified CA1 neuronal input/output dynamics, these alterations were not sufficient to impair active avoidance spatial behavior.SignificanceThese findings indicate that although eRFSs do not result in spatial cognitive deficits in the active avoidance task, recurrent seizures do alter the brain and result in longstanding changes in the temporal organization of the hippocampus.

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by dementia. Inhibition of soluble epoxide hydrolase (sEH) regulates inflammation involving in central nervous system (CNS) diseases. However, the exactly mechanism of sEH in AD is still unclear. In this study, we evaluated the vital role of sEH in amyloid beta (Aβ)-induced AD mice, and revealed a possible molecular mechanism for inhibition of sEH in the treatment of AD. The results showed that the sEH expression and activity were remarkably increased in the hippocampus of Aβ-induced AD mice. Chemical inhibition of sEH by TPPU, a selective sEH inhibitor, alleviated spatial learning and memory deficits, and elevated levels of neurotransmitters in Aβ-induced AD mice. Furthermore, inhibition of sEH could ameliorate neuroinflammation, neuronal death, and oxidative stress via stabilizing the in vivo level of epoxyeicosatrienoic acids (EETs), especially 8,9-EET and 14,15-EET, further resulting in the anti-AD effect through the regulation of GSK3β-mediated NF-κB, p53, and Nrf2 signaling pathways. These findings revealed the underlying mechanism of sEH as a potential therapeutic target in treatment of AD.

The biological mechanisms underpinning learning are unclear. Mounting evidence has suggested that adult hippocampal neurogenesis is involved although a causal relationship has not been well defined. Here, using high-resolution genetic mapping of adult neurogenesis, combined with sequencing information, we identify follistatin (Fst) and demonstrate its involvement in learning and adult neurogenesis. We confirmed that brain-specific Fst knockout (KO) mice exhibited decreased hippocampal neurogenesis and demonstrated that FST is critical for learning. Fst KO mice exhibit deficits in spatial learning, working memory, and long-term potentiation (LTP). In contrast, hippocampal overexpression of Fst in KO mice reversed these impairments. By utilizing RNA sequencing and chromatin immunoprecipitation, we identified Asic4 as a target gene regulated by FST and show that Asic4 plays a critical role in learning deficits caused by Fst deletion. Long-term overexpression of hippocampal Fst in C57BL/6 wild-type mice alleviates age-related decline in cognition, neurogenesis, and LTP. Collectively, our study reveals the functions for FST in adult neurogenesis and learning behaviors.

Eels migrate long distances and their spatial learning ability based on extra-maze visual cues has been examined in the laboratory. Here, I examine the discriminative properties of water flow in their spatial cognition. Individuals of the Japanese eel (Anguilla japonica) were trained in a circular pool containing four pipes. One pipe was open where the eels could enter, and the other pipes were closed. A small motor-driven water screw was placed beside each pipe. The water screw close to the open pipe was active to allow water flow, whereas the other screws were inactive. The position of the open pipe with the active screw was randomly changed, and the eels could learn the position of the open pipe after approximately 15 trials. Overall, five tests were conducted. Test 1: A generalization test showed a generalization gradient along the distance from the open pipe and the active screw. Test 2: A test using a screw with no blades (i.e., no water flow but possible vibration or sound by a motor is present) resulted in chance level performance, suggesting that the eels needed water flow to find the open pipe. Test 3: A test with a water pump that produced water flow by a mechanism different from that of the original motor-driven screw showed that the eels maintained the detection of water flow under this condition. Test 4: The eels also located the open pipe in a dark room test; therefore, visual cues were not used for the detection of the open pipe. To confirm that the water flow was detected by the lateral organ, streptomycin sulfate was dissolved in a home tank to impair the hair cells in the lateral line organ in Test 5, and the eels were not able to detect the open pipe under these conditions. This observation suggests that the detection of water flow depends on the lateral-line organ. In summary, the data show that eels can detect water flow to find hiding locations.

Cue competition is a key element of many associative theories of learning. Overshadowing, an important aspect of cue competition, is a phenomenon in which learning about a cue is reduced when it is accompanied by a second cue. Overshadowing has been observed across many domains, but there has been limited investigation of overshadowing in human spatial learning. This experiment explored overshadowing using two landmarks/cues (at different distances to the goal) in a virtual water maze task with young, healthy adult participants. Experiment 1 initially examined whether the cues used were equally salient. Results indicated that both gained equal control over performance. In experiment 2, overshadowing was examined using the two cues from experiment 1. Results indicated that overshadowing occurred during spatial learning and that the near cue controlled searching significantly more than the far cue. Furthermore, the far cue appeared to have been completely ignored, suggesting that learning strategies requiring the least amount of effort were employed by participants. Evidence supporting an associative account of human spatial navigation and the influence of proximal cues was discussed. [ABSTRACT FROM AUTHOR]

Myriad research in a variety of contexts shows spatial skills benefit students; however, they are not given enough attention in classroom instruction. In this review we systematically explore geoscience education literature focusing on spatial interventions to answer research questions on trends in spatial skills and other characteristics. We narrow our attention to studies published since numerous calls to action to teach more spatial skills in STEM education, resulting in 28 articles for review. To analyse and compare these studies, we organise the literature into a framework of geoscience-relevant spatial skills. We reviewed interventions and assessments to determine the aligning spatial typology skills. Themes of coursework, mapping, and modelling emerged; sub-themes include sketching, gestures, physical models, computer models, and curricular interventions. In the articles reviewed, just over half of the skills identified were intrinsic skills. Future geospatial research should explore how best to incorporate spatial skills into the classroom over long time periods and should focus on the process of spatial reasoning and the strategies students use when problem-solving about spatial phenomena, especially at the elementary and secondary school level. Educators can use the resources outlined in this review to engage in spatialising their curricula. [ABSTRACT FROM AUTHOR]

Estrogens regulate synaptic properties and influence hippocampus-related learning and memory via estrogen receptors, which include the G-protein-coupled estrogen receptor 1 (GPER1). Studying mice, in which the GPER1 gene is dysfunctional (GPER1-KO), we here provide evidence for sex-specific roles of GPER1 in these processes. GPER1-KO males showed reduced anxiety in the elevated plus maze, whereas the fear response ('freezing') was specifically increased in GPER1-KO females in a contextual fear conditioning paradigm. In the Morris water maze, spatial learning and memory consolidation was impaired by GPER1 deficiency in both sexes. Notably, in the females, spatial learning deficits and the fear response were more pronounced if mice were in a stage of the estrous cycle, in which E2 serum levels are high (proestrus) or rising (diestrus). On the physiological level, excitability at Schaffer collateral synapses in CA1 increased in GPER1-deficient males and in proestrus/diestrus ('E2 high') females, concordant with an increased hippocampal expression of the AMPA-receptor subunit GluA1 in GPER1-KO males and females as compared to wildtype males. Further changes included an augmented early long-term potentiation (E-LTP) maintenance specifically in GPER1-KO females and an increased hippocampal expression of spinophilin in metestrus/estrus ('E2 low') GPER1-KO females. Our findings suggest modulatory and sex-specific functions of GPER1 in the hippocampal network, which reduce rather than increase neuronal excitability. Dysregulation of these functions may underlie sex-specific cognitive deficits or mood disorders. [ABSTRACT FROM AUTHOR]

Introduction: A significant interaction exists between hippocampal circuitry and several modulatory neurotransmitters, such as dopamine (DA). In recent studies, dopaminergic fibers from the locus coeruleus (LC) to the hippocampus have been emphasized. In particular, it has been shown that axons are terminating in the dorsal hippocampus from the LC, which, in addition to norepinephrine, also release DA. Considering the firing patterns (tonic and phasic) of LC neurons and the dorsal hippocampus’s role in spatial learning and memory, the effects of unilateral patterned electrical stimulation of mouse locus coeruleus on spatial learning and memory were studied. Methods and Materials: In this study, C57BL/6 mice were used. A tripolar stainless steel electrode was implanted into the LC, and a head socket was fitted. After surgery, the animal is connected to a miniature buffer head stage for electrical stimulation. LC was stimulated with tonic (1 Hz) or phasic (24 Hz) stimulation protocol. To assess behavioral tasks and LC stimulation interaction effects, we conducted multiple experiments combining behavior and electrical neuromodulator activation. For this, mice were trained with electrical stimulation in the Barnes task (4D stimulation). Results: We found that phasic LC modulation treatment enhanced spatial learning and memory, but tonic stimulation impaired it. Conclusion: It is concluded that LC stimulation by phasic pattern, not tonic, improved spatial learning and memory. Using a phasic pattern might affect the hippocampal dopaminergic fibers, releasing a high amount of dopamine and activating D1-like receptors with low affinity. Furthermore, dopamine D1-like receptor activation increases synaptic strength and relates to long-term potentiation. This finding indicates the effectiveness of the phasic stimulation pattern in activating dopamine release and the involvement of dopamine D1 receptors in spatial memory by LC phasic activation. [ABSTRACT FROM AUTHOR]

Aging is associated with impairments in learning, memory, and cognitive flexibility, as well as a gradual decline in hippocampal neurogenesis. We investigated the performance of 6-and 14-month-old mice (considered mature adult and late middle age, respectively) in learning and memory tasks based on the Morris water maze (MWM) and determined their levels of preceding and current neurogenesis. While both age groups successfully performed in the spatial version of MWM (sMWM), the older mice were less efficient compared to the younger mice when presented with modified versions of the MWM that required a reassessment of the previously acquired experience. This was detected in the reversal version of MWM (rMWM) and was particularly evident in the context discrimination MWM (cdMWM), a novel task that required integrating various distal cues, local cues, and altered contexts and adjusting previously used search strategies. Older mice were impaired in several metrics that characterize rMWM and cdMWM, however, they showed improvement and narrowed the performance gap with the younger mice after additional training. Furthermore, we analyzed the adult-born mature and immature neurons in the hippocampal dentate gyrus and found a significant correlation between neurogenesis levels in individual mice and their performance in the tasks demanding cognitive flexibility. These results provide a detailed description of the age-related changes in learning and memory and underscore the importance of hippocampal neurogenesis in supporting cognitive flexibility. [ABSTRACT FROM AUTHOR]