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Long-term memory formation requires de novo RNA and protein synthesis. Using differential display PCR, we found that the NCoR1 cDNA fragment is differentially expressed between fast learners and slow learners, with fast learners showing a lower expression level than slow learners in the water maze learning task. Fast learners also show lower NCoR1 mRNA and protein expression levels. In addition, spatial training decreases both NCoR1 mRNA and protein expression, whereas NCoR1 conditional knockout (cKO) mice show enhanced spatial memory. In studying the molecular mechanism, we found that spatial training decreases the association between NCoR1 and DEC2. Both NCoR1 and DEC2 suppress the expression of BDNF, integrin α3 and SGK1 through C/EBPα binding to their DNA promoters, but overexpression of DEC2 in NCoR1 cKO mice rescues the decreased expression of these proteins compared with NCoR1 loxP mice overexpressing DEC2. Further, spatial training decreases DEC2 expression. Spatial training also enhances C/EBPα binding to Bdnf, Itga3 and Sgk1 promoters, an effect also observed in fast learners, and both NCoR1 and DEC2 control C/EBPα activity. Whereas knockdown of BDNF, integrin α3 or SGK1 expression impairs spatial learning and memory, it does not affect Y-maze performance, suggesting that BDNF, integrin α3 and SGK1 are involved in long-term memory formation, but not short-term memory formation. Moreover, NCoR1 expression is regulated by the JNK/c-Jun signaling pathway. Collectively, our findings identify DEC2 as a novel interacting protein of NCoR1 and elucidate the novel roles and mechanisms of NCoR1 and DEC2 in negative regulation of spatial memory formation. [ABSTRACT FROM AUTHOR]

Increased vulnerability to seizures in aging has been well documented both clinically and in various models of aging in epilepsy. Seizures can exacerbate cognitive decline that is already prominent in aging. Senescent cells are thought to contribute to cognitive impairment in aging and clearing senescent cells with senolytic drugs improves cognitive function in animal models. It remains unclear whether senescent cells render the aged brain vulnerable to seizures. Here, we demonstrate that prophylactic senolytic treatment with Dasatinib and Quercetin (D&Q) reduced both seizure severity and mortality in aged C57BL/6J mice. We subjected the D&Q and VEH‐treated aged mice to spatial memory testing before and after an acute seizure insult, Status Epilepticus [SE], which leads to epilepsy development. We found that senolytic therapy improved spatial memory before injury, however, spatial memory was not rescued after SE. Senescence‐related proteins p16 and senescence‐associated β‐galactosidase were reduced in D&Q‐treated aged mice. Our findings indicate that senescent cells increase seizure susceptibility in aging. Thus, prophylactically targeting senescent cells may prevent age‐related seizure vulnerability. [ABSTRACT FROM AUTHOR]

Augmented reality (AR) technology allows virtual objects to be superimposed on the real‐world environment, offering significant potential for improving cognitive assessments and rehabilitation processes in the field of visuospatial learning. This study examines how patients with acquired brain injury (ABI) evaluate the functions and usability of a SLAM‐based smartphone AR app to assess object‐location skills. Ten ABI patients performed a task for the spatial recall of four objects using an AR app. The data collected from 10 healthy participants provided reference values for the best performance. Their perceptions of the AR app/technology and its usability were investigated. The results indicate lower effectiveness in solving the task in the patient group, as the time they needed to complete it was related to their level of impairment. The patients showed lower, yet positive, scores in factors related to app usability and acceptance (e.g., mental effort and satisfaction, respectively). There were more patients reported on entertainment as a positive aspect of the app. Patients' perceived enjoyment was related to concentration and calm, whereas usability was associated with perceived competence, expertise, and a lower level of physical effort. For patients, the sensory aspects of the objects were related to their presence, while for healthy participants, they were related to enjoyment and required effort. The results show that AR seems to be a promising tool to assess spatial orientation in the target patient population. [ABSTRACT FROM AUTHOR]

In their natural environment, animals face a variety of ecological and social challenges, which might be linked to the emergence of different cognitive skills. To assess inter-specific variation in cognitive skills, we used ungulates as a study model, testing a total of 26 captive individuals across 5 different species (i.e., dwarf goats, Capra aegagrus hircus, llamas, Lama glama, guanacos, Lama guanicoe, zebras, Equus grevyi, and rhinos, Diceros bicornis michaeli). Across species, we used the same well-established experimental procedures to test individuals' performance in naïve physics tasks, i.e. object permanence, short-term spatial memory, causality, understanding of object properties, and gravity. Our results revealed that study subjects showed object permanence, were able to remember the position of hidden food after up to 60 s, and inferred the position of hidden food from the sound produced or not produced when shaking containers. Moreover, they showed an understanding of basic object properties, being able to locate objects hidden behind occluders based on their size and inclination, and could reliably follow the trajectory of falling objects across different conditions. Finally, inter-specific differences were limited to the understanding of object properties, and suggest that domesticated species as goats might perform better than non-domesticated ones in tasks requiring these skills. These results provide new information on the cognitive skills of a still understudied taxon and confirm ungulates as a promising taxon for the comparative study of cognitive evolution. [ABSTRACT FROM AUTHOR]

AbstractMultiple sclerosis (MS) is a condition characterized by inflammation in the central nervous system (CNS), impacting sensory, motor, and cognitive abilities. Globally, around three million individuals are affected by MS, with up to 97,000 cases in Iran attributed to genetic predispositions along with various environmental factors like smoking. Cognitive impairment affects a significant portion of patients, ranging from 45% to 70%. This study investigates the impact of regular aerobic swimming exercise for four weeks, mild cognitive impairment induced by encephalomyelitis, and their combination on the expression of microRNA-142-3p and its correlation with the release of brain-derived neurotrophic factor (BDNF) in relation to spatial memory. Twenty-one C57BL/6 mice were divided into three groups. RT-PCR was used for microRNA expression analysis, and BDNF levels were assessed via western blotting. Clinical scores and animal weights were monitored daily. EAE induction led to an increase in microRNA-142-3p expression and a decrease in BDNF levels compared to the control group. Exercise inversed them significantly, and improved spatial memory. Our findings indicate that engaging in regular swimming exercise can counteract the up-regulation of miR-142-3p in brain tissue, which likely contributes to mild cognitive impairment induced by MS. Additionally, the increase in BDNF following exercise appears to be associated with miR-142-3p and the enhancement of cognitive function. Thus, the therapeutic benefits of exercise, particularly in releasing BDNF to improve cognitive function in MS patients, warrant consideration. Lifestyle modifications have the potential to effectively modulate environmental influences and ethnicity, underscoring their significance in MS management. [ABSTRACT FROM AUTHOR]

• In preclinical models, fructose induces deficits in spatial and recognition memory. • Female rodents are more resistant to memory impairment induced by fructose. • Neuroinflammation and oxidative stress are short-term underlying mechanisms. • Fructose intake triggers neurogenesis inhibition and LTP decay in the long term. • Clinical data suggest an association between fructose and memory impairment. Fructose consumption has increased over the years, especially in adolescents living in urban areas. Growing evidence indicates that daily fructose consumption leads to some pathological conditions, including memory impairment. This review summarizes relevant data describing cognitive deficits after fructose intake and analyzes the underlying neurobiological mechanisms. Preclinical experiments show sex-related deficits in spatial memory; that is, while males exhibit significant imbalances in spatial processing, females seem unaffected by dietary supplementation with fructose. Recognition memory has also been evaluated; however, only female rodents show a significant decline in the novel object recognition test performance. According to mechanistic evidence, fructose intake induces neuroinflammation, mitochondrial dysfunction, and oxidative stress in the short term. Subsequently, these mechanisms can trigger other long-term effects, such as inhibition of neurogenesis, downregulation of trophic factors and receptors, weakening of synaptic plasticity, and long-term potentiation decay. Integrating all these neurobiological mechanisms will help us understand the cellular and molecular processes that trigger the memory impairment induced by fructose. [ABSTRACT FROM AUTHOR]

The behavioral and neural effects of the endogenous release of acetylcholine following stimulation of the nucleus basalis (NB) of Meynert have been recently examined in two male monkeys (Qi et al., 2021). Counterintuitively, NB stimulation enhanced behavioral performance while broadening neural tuning in the prefrontal cortex (PFC). The mechanism by which a weaker mnemonic neural code could lead to better performance remains unclear. Here, we show that increased neural excitability in a simple continuous bump attractor model can induce broader neural tuning and decrease bump diffusion, provided neural rates are saturated. Increased memory precision in the model overrides memory accuracy, improving overall task performance. Moreover, we show that bump attractor dynamics can account for the nonuniform impact of neuromodulation on distractibility, depending on distractor distance from the target. Finally, we delve into the conditions under which bump attractor tuning and diffusion balance in biologically plausible heterogeneous network models. In these discrete bump attractor networks, we show that reducing spatial correlations or enhancing excitatory transmission can improve memory precision. Altogether, we provide a mechanistic understanding of how cholinergic neuromodulation controls spatial working memory through perturbed attractor dynamics in the PFC. [ABSTRACT FROM AUTHOR]

Sex differences have been found in allocentric spatial learning and memory tasks, with the literature indicating that males outperform females, although this issue is still controversial. This study aimed to explore the behavior of male and female rats during the habituation and learning of a spatial memory task performed in the Morris Water Maze (MWM). The study included a large sample of 89 males and 85 females. We found that females searched slightly faster than males during habituation with a visible platform. During learning, both male and female rats decreased the latency and distance traveled to find the hidden platform over the days, with males outperforming females in the distance traveled. Females swam faster but did not find the platform earlier, suggesting a less directed navigational strategy. Both sexes increased time spent in the target zone over the days, with no sex differences. Although females swam more in the periphery during the first days of the task, both sexes decreased the time spent in this area. Finally, only males increased swimming in the pool's center over the days, spending more time than females in this area across the entire training. In conclusion, we need to register several variables in the MWM and analyze path strategies to obtain more robust results concerning sex differences. Research on spatial learning should include both sexes to achieve a more equitable, representative, and translational science. [ABSTRACT FROM AUTHOR]

Background: Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. Objective: We aimed to assess navigation cues for innovative spatial training in aging. Methods: Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Results: Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. Conclusions: These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded. [ABSTRACT FROM AUTHOR]

Our ability to navigate in a new environment depends on learning new locations. Mental representations of locations are quickly accessible during navigation and allow us to know where we are regardless of our current viewpoint. Recent functional magnetic resonance imaging (fMRI) research using pattern classification has shown that these location‐based representations emerge in the retrosplenial cortex and parahippocampal gyrus, regions theorized to be critically involved in spatial navigation. However, little is currently known about the oscillatory dynamics that support the formation of location‐based representations. We used magnetoencephalogram (MEG) recordings to investigate region‐specific oscillatory activity in a task where participants could form location‐based representations. Participants viewed videos showing that two perceptually distinct scenes (180° apart) belonged to the same location. This "overlap" video allowed participants to bind the two distinct scenes together into a more coherent location‐based representation. Participants also viewed control "non‐overlap" videos where two distinct scenes from two different locations were shown, where no location‐based representation could be formed. In a post‐video behavioral task, participants successfully matched the two viewpoints shown in the overlap videos, but not the non‐overlap videos, indicating they successfully learned the locations in the overlap condition. Comparing oscillatory activity between the overlap and non‐overlap videos, we found greater theta and alpha/beta power during the overlap relative to non‐overlap videos, specifically at time‐points when we expected scene integration to occur. These oscillations localized to regions in the medial parietal cortex (precuneus and retrosplenial cortex) and the medial temporal lobe, including the hippocampus. Therefore, we find that theta and alpha/beta oscillations in the hippocampus and medial parietal cortex are likely involved in the formation of location‐based representations. [ABSTRACT FROM AUTHOR]

In this research, we examine a diffusive predator–prey model with spatial memory. We begin by checking that the suggested model has a unique solution that is boundedness. The stability of each equilibrium is then examined. Local and global stability as well as bifurcations are investigated in the non-delayed model at stationary equilibrium. Then, we investigate the Hopf bifurcation using the delay as the bifurcation parameter. In order to back up our theoretical findings, we then give some numerical simulations. [ABSTRACT FROM AUTHOR]

Multiple sensorimotor loops converge in the motor cortex to create an adaptable system capable of context-specific sensorimotor control. Afferent inhibition provides a non-invasive tool to investigate the substrates by which procedural and cognitive control processes interact to shape motor corticospinal projections. Varying the transcranial magnetic stimulation properties during afferent inhibition can probe specific sensorimotor circuits that contribute to short- and long-latency periods of inhibition in response to the peripheral stimulation. The current study used short- (SAI) and long-latency (LAI) afferent inhibition to probe the influence of verbal and spatial working memory load on the specific sensorimotor circuits recruited by posterior-anterior (PA) and anterior-posterior (AP) TMS-induced current. Participants completed two sessions where SAI and LAI were assessed during the short-term maintenance of two- or six-item sets of letters (verbal) or stimulus locations (spatial). The only difference between the sessions was the direction of the induced current. PA SAI decreased as the verbal working memory load increased. In contrast, AP SAI was not modulated by verbal working memory load. Visuospatial working memory load did not affect PA or AP SAI. Neither PA LAI nor AP LAI were sensitive to verbal or spatial working memory load. The dissociation of short-latency PA and AP sensorimotor circuits and short- and long-latency PA sensorimotor circuits with increasing verbal working memory load support multiple convergent sensorimotor loops that provide distinct functional information to facilitate context-specific supraspinal control. [ABSTRACT FROM AUTHOR]

Brain oscillations in humans play a role in a wide range of cognitive processes, including navigation and memory. The oscillatory dynamics contributing to successful spatial memory recall in humans are not well-understood. To investigate specific oscillatory frequency bands during the recall process in human navigation, we recorded electroencephalographic (EEG) activity during a recall trial in healthy young adults (n = 15) following the learning of a goal location in a Virtual Water Maze task. We compared this to the activity during the same trial length, in a group of participants who did not learn a target location and navigated freely but were time-matched to the learning group (non-learning, n = 15). We compared relative power in Delta (2-4Hz), Theta (5-7Hz), Alpha (8-12Hz), Beta (15-29Hz), and Gamma (30-40Hz) bands across the scalp. We found that delta and theta activity were greater during recall in our learning group, as opposed to our non-learning group. We also demonstrated clear suppression in the alpha band at posterior sites during memory-guided navigation compared to our non-learning group. Additionally, when goal-directed navigation switches to focused searching behavior, power becomes greater at the frontal region; with increases in the delta and theta bands reflecting this strategy change. There was also greater beta and gamma activity at posterior sites in our learning group. We discuss the results further in terms of the possible roles and functions of these oscillations during human navigation and hope this exploratory analysis can provide hypotheses for future spatial navigation and memory work. [ABSTRACT FROM AUTHOR]

Background and aim: Vascular dementia (VD) is a common type of dementia. This study aimed to evaluate the effects of low and high doses of lutein administration in bilateral-carotid vessel occlusion (2VO) rats. Experimental procedure: The rats were divided into the following groups: the control, sham-, vehicle (2VO+V) groups, and two groups after 2VO were treated with lutein 0.5 (2VO+LUT-o.5) and 5mg/kg (2VO+LUT-5). The passive-avoidance and Morris water maze were performed to examine fear and spatial memory. The field-potential recording was used to investigate the properties of basal synaptic transmission (BST), paired-pulse ratio (PPR), as an index for measurement of neurotransmitter release, and long-term potentiation (LTP). The hippocampus was removed to evaluate hippocampal cells, volume, and MDA level. Result: Treatment with low and high doses improves spatial memory and LTP impairment in VD rats, but only the high dose restores the fear memory, hippocampal cell loss, and volume and MDA level. Interestingly, low-dose, but not high-dose, increased PPR. However, BST recovered only in the high-dose treated group. Conclusions: Treatment with a low dose might affect neurotransmitter release probability, but a high dose affects postsynaptic processes. It seems likely that low and high doses improve memory and LTP through different mechanisms. [ABSTRACT FROM AUTHOR]

In a changing environment, animals must process spatial signals in a flexible manner. The rat hippocampal formation projects directly upon the retrosplenial cortex, with most inputs arising from the dorsal subiculum and terminating in the granular retrosplenial cortex (area 29). The present study examined whether these same projections are required for spatial working memory and what happens when available spatial cues are altered. Consequently, injections of iDREADDs were made into the dorsal subiculum of rats. In a separate control group, GFP‐expressing adeno‐associated virus was injected into the dorsal subiculum. Both groups received intracerebral infusions within the retrosplenial cortex of clozapine, which in the iDREADDs rats should selectively disrupt the subiculum to retrosplenial projections. When tested on reinforced T‐maze alternation, disruption of the subiculum to retrosplenial projections had no evident effect on the performance of those alternation trials when all spatial‐cue types remained present and unchanged. However, the same iDREADDs manipulation impaired performance on all three alternation conditions when there was a conflict or selective removal of spatial cues. These findings reveal how the direct projections from the dorsal subiculum to the retrosplenial cortex support the flexible integration of different spatial cue types, helping the animal to adopt the spatial strategy that best meets current environmental demands. [ABSTRACT FROM AUTHOR]

Spatial navigation is a multi-faceted behaviour drawing on many different aspects of cognition. Visuospatial abilities, such as mental rotation and visuospatial working memory, in particular, may be key factors. A range of tests have been developed to assess visuospatial processing and memory, but how such tests relate to navigation ability remains unclear. This understanding is important to advance tests of navigation for disease monitoring in various disorders (e.g., Alzheimer's disease) where spatial impairment is an early symptom. Here, we report the use of an established mobile gaming app, Sea Hero Quest (SHQ), as a measure of navigation ability in a sample of young, predominantly female university students (N = 78; 20; female = 74.3%; mean age = 20.33 years). We used three separate tests of navigation embedded in SHQ: wayfinding, path integration and spatial memory in a radial arm maze. In the same participants, we also collected measures of mental rotation (Mental Rotation Test), visuospatial processing (Design Organization Test) and visuospatial working memory (Digital Corsi). We found few strong correlations across our measures. Being good at wayfinding in a virtual navigation test does not mean an individual will also be good at path integration, have a superior memory in a radial arm maze, or rate themself as having a strong sense of direction. However, we observed that participants who were good in the wayfinding task of SHQ tended to perform well on the three visuospatial tasks examined here, and to also use a landmark strategy in the radial maze task. These findings help clarify the associations between different abilities involved in spatial navigation. [ABSTRACT FROM AUTHOR]

Rationale: Animal studies suggest that the so-called "female" hormone estrogen enhances spatial navigation and memory. This contradicts the observation that males generally out-perform females in spatial navigation and tasks involving spatial memory. A closer look at the vast number of studies actually reveals that performance differences are not so clear. Objectives: To help clarify the unclear performance differences between men and women and the role of estrogen, we attempted to isolate organizational from activational effects of estrogen on spatial navigation and memory. Methods: In a double-blind, placebo-controlled study, we tested the effects of orally administered estradiol valerate (E2V) in healthy, young women in their low-hormone menstrual cycle phase, compared to healthy, young men. Participants performed several first-person, environmentally rich, 3-D computer games inspired by spatial navigation and memory paradigms in animal research. Results: We found navigation behavior suggesting that sex effects dominated any E2 effects with men performing better with allocentric strategies and women with egocentric strategies. Increased E2 levels did not lead to general improvements in spatial ability in either sex but to behavioral changes reflecting navigation flexibility. Conclusion: Estrogen-driven differences in spatial cognition might be better characterized on a spectrum of navigation flexibility rather than by categorical performance measures or skills. [ABSTRACT FROM AUTHOR]

• The CYSLTR1 antagonist montelukast protects neurons from macrophage neurotoxicity induced by HIV-1 or HIVgp120 protein. • HIV-1 infection or exposure to HIVgp120 increases CysLT release by macrophages and inhibition of p38 MAPK abrogates elevated CysLT production. • Cerebral cortex of HIV+ individuals with pathology expresses more CYSLTR1 than that of HIV+ persons without pathology or uninfected individuals. • Genetic ablation of Ltc4s or Cysltr1 in HIVgp120-transgenic mice results in complete neuroprotection and preserved memory function. • Genetic ablation of Ltc4s or Cysltr1 in mice reveals a physiological role of CysLTs in memory function and sexual dimorphisms in glial cells. Macrophages (MΦ) infected with human immunodeficiency virus (HIV)-1 or activated by its envelope protein gp120 exert neurotoxicity. We found previously that signaling via p38 mitogen-activated protein kinase (p38 MAPK) is essential to the neurotoxicity of HIVgp120-stimulated MΦ. However, the associated downstream pathways remained elusive. Here we show that cysteinyl-leukotrienes (CysLT) released by HIV-infected or HIVgp120 stimulated MΦ downstream of p38 MAPK critically contribute to neurotoxicity. SiRNA-mediated or pharmacological inhibition of p38 MAPK deprives MΦ of CysLT synthase (LTC4S) and, pharmacological inhibition of the cysteinyl-leukotriene receptor 1 (CYSLTR1) protects cerebrocortical neurons against toxicity of both gp120-stimulated and HIV-infected MΦ. Components of the CysLT pathway are differentially regulated in brains of HIV-infected individuals and a transgenic mouse model of NeuroHIV (HIVgp120tg). Moreover, genetic ablation of LTC4S or CysLTR1 prevents neuronal damage and impairment of spatial memory in HIVgp120tg mice. Altogether, our findings suggest a novel critical role for cysteinyl-leukotrienes in HIV-associated brain injury. [ABSTRACT FROM AUTHOR]

• Genetic ablation of IFNβ modulates HIVgp120-induced neuropathology in a sex-dependent fashion. • Endogenous IFNβ is required for normal function of spatial and recognition memory. • Genetic ablation of IFNβ aggravates impairment of spatial memory in the presence of HIVgp120. • Endogenous IFNβ regulates expression of neuroinflammatory factors induced during exposure to HIVgp120. • Genetic ablation of IFNβ alters expression of neurotransmission-related genes in a sex-dependent fashion. Human immunodeficiency virus-1 (HIV-1) infects the central nervous system (CNS) and causes HIV-associated neurocognitive disorders (HAND) in about half of the population living with the virus despite combination anti-retroviral therapy (cART). HIV-1 activates the innate immune system, including the production of type 1 interferons (IFNs) α and β. Transgenic mice expressing HIV-1 envelope glycoprotein gp120 (HIVgp120tg) in the CNS develop memory impairment and share key neuropathological features and differential CNS gene expression with HIV patients, including the induction of IFN-stimulated genes (ISG). Here we show that knocking out IFNβ (IFNβKO) in HIVgp120tg and non-tg control mice impairs recognition and spatial memory, but does not affect anxiety-like behavior, locomotion, or vision. The neuropathology of HIVgp120tg mice is only moderately affected by the KO of IFNβ but in a sex-dependent fashion. Notably, in cerebral cortex of IFNβKO animals presynaptic terminals are reduced in males while neuronal dendrites are reduced in females. The IFNβKO results in the hippocampal CA1 region of both male and female HIVgp120tg mice in an ameliorated loss of neuronal presynaptic terminals but no protection of neuronal dendrites. Only female IFNβ-deficient HIVgp120tg mice display diminished microglial activation in cortex and hippocampus and increased astrocytosis in hippocampus compared to their IFNβ-expressing counterparts. RNA expression for some immune genes and ISGs is also affected in a sex-dependent way. The IFNβKO abrogates or diminishes the induction of MX1, DDX58, IRF7 and IRF9 in HIVgp120tg brains of both sexes. Expression analysis of neurotransmission related genes reveals an influence of IFNβ on multiple components with more pronounced changes in IFNβKO females. In contrast, the effects of IFNβKO on MAPK activities are independent of sex with pronounced reduction of active ERK1/2 but also of active p38 in the HIVgp120tg brain. In summary, our findings show that the absence of IFNβ impairs memory dependent behavior and modulates neuropathology in HIVgp120tg brains, indicating that its absence may facilitate development of HAND. Moreover, our data suggests that endogenous IFNβ plays a vital role in maintaining neuronal homeostasis and memory function. [ABSTRACT FROM AUTHOR]

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p <.05). Subjective Contentedness (p <.01) and Amicability (p <.05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au) [ABSTRACT FROM AUTHOR]

The methylazoxymethanol acetate (MAM) rodent model is used to study aspects of schizophrenia. However, numerous studies that have employed this model have used only males, resulting in a dearth of knowledge on sex differences in brain function and behaviour. The purpose of this study was to determine whether differences exist between male and female MAM rats in neuronal oscillatory function within and between the prefrontal cortex (PFC), ventral hippocampus (vHIP) and thalamus, behaviour, and in proteins linked to schizophrenia neuropathology. We showed that female MAM animals exhibited region-specific alterations in theta power, elevated low and high gamma power in all regions, and elevated PFC-thalamus high gamma coherence. Male MAM rats had elevated beta and low gamma power in PFC, and elevated vHIP-thalamus coherence. MAM females displayed impaired reversal learning whereas MAM males showed impairments in spatial memory. Glycogen synthase kinase-3 (GSK-3) was altered in the thalamus, with female MAM rats displaying elevated GSK-3α phosphorylation. Male MAM rats showed higher expression and phosphorylation GSK-3α, and higher expression of GSK-β. Sex-specific changes in phosphorylated Tau levels were observed in a region-specific manner. These findings demonstrate there are notable sex differences in behaviour, oscillatory network function, and GSK-3 signaling in MAM rats, thus highlighting the importance of inclusion of both sexes when using this model to study schizophrenia. [ABSTRACT FROM AUTHOR]

Recent work has examined the interaction between space and time in memory search, but there is still limited understanding of this relationship. Here, we test the hypothesis that individuals can exert control over how time and space interact in response to subtle differences in task instructions. To test this hypothesis, we analyzed two experiments where participants completed two immediate free recall tasks, a verbal task involving words presented at a central location and a spatial task involving squares presented at different locations. Some participants were free to recall the words or locations spontaneously in any order they preferred. In contrast, another group was subtly biased toward temporal information by instructions to begin recall from the last presented item before recalling the remaining items in any order they wished. Replicating recent work, all conditions showed clear evidence that recall was organized along both the temporal and the spatial dimensions. Extending this work, we found that the subtle change in recall instructions increased the reliance on temporal information in the spatial recall task. Correlational analyses suggest that spatial and temporal information do not compete when participants search memory spontaneously. However, they do compete when instructions favor temporal information. These findings highlight that individuals can exert some cognitive control over how associative dimensions interact during memory search and emphasize the importance of incorporating such processes into theoretical models. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n = 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8‐arm radial arm maze win‐shift task. Comparing rats' behaviour in the two arm types showed that rearing frequency was not changed, but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n = 6 rats). Optogenetic inhibition of cholinergic neurons during the pretrial waiting phase had no significant effect on rearing, indicating a context‐specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing. [ABSTRACT FROM AUTHOR]

Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non‐human primates, and humans. By contrast, damage to the hippocampus spares performance in most non‐navigational spatial memory tasks—which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self‐ordered non‐navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network‐based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non‐human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non‐navigational spatial memory, and help to reconcile the many null findings previously reported. [ABSTRACT FROM AUTHOR]

Most animals live in spatially-constrained home ranges. The prevalence of this space-use pattern in nature suggests that general biological mechanisms are likely to be responsible for their occurrence. Individual-based models of animal movement in both theoretical and empirical settings have demonstrated that the revisitation of familiar areas through memory can lead to the formation of stable home ranges. Here, we formulate a deterministic, mechanistic home range model that includes the interplay between a bi-component memory and resource preference, and evaluate resulting patterns of space-use. We show that a bi-component memory process can lead to the formation of stable home ranges and control its size, with greater spatial memory capabilities being associated with larger home range size. The interplay between memory and resource preferences gives rise to a continuum of space-use patterns–from spatially-restricted movements into a home range that is influenced by local resource heterogeneity, to diffusive-like movements dependent on larger-scale resource distributions, such as in nomadism. Future work could take advantage of this model formulation to evaluate the role of memory in shaping individual performance in response to varying spatio-temporal resource patterns. [ABSTRACT FROM AUTHOR]

This study examined the influence of genetic background on cognitive performance in a selectively bred high nicotine-preferring (NP) rat line. Using the novel object recognition (NOR), novel location recognition (NLR), and Morris water maze (MWM) tests, we evaluated object memory, spatial memory, and spatial navigation in nicotine-naive NP rats compared to controls. Our results demonstrate that in the NOR test, both male and female NP rats spent more time exploring the novel object (higher discrimination index) compared to sex-matched controls. In the NLR, the discrimination index differed significantly from zero chance (no preference) in both NP males and females but not in controls, indicating enhanced spatial memory in the NP line. During MWM acquisition, the NP groups and control males took a shorter path to reach the platform compared to control females. On the probe trial, the distance traveled in the target quadrant was longer for NP males and females compared to their respective controls, suggesting enhanced spatial navigation and learning in the NP rats. The interesting preference for novel objects and locations displayed by NP rats may indicate a potential novelty-seeking phenotype in this line. These results highlight the complex interplay between genetic factors, cognitive function, and nicotine preference. [ABSTRACT FROM AUTHOR]

One potential application of forensic "brain reading" is to test whether a suspect has previously experienced a crime scene. Here, we investigated whether it is possible to decode real life autobiographic exposure to spatial locations using fMRI. In the first session, participants visited four out of eight possible rooms on a university campus. During a subsequent scanning session, subjects passively viewed pictures and videos from these eight possible rooms (four old, four novel) without giving any responses. A multivariate searchlight analysis was employed that trained a classifier to distinguish between "seen" versus "unseen" stimuli from a subset of six rooms. We found that bilateral precuneus encoded information that can be used to distinguish between previously seen and unseen rooms and that also generalized to the two stimuli left out from training. We conclude that activity in bilateral precuneus is associated with the memory of previously visited rooms, irrespective of the identity of the room, thus supporting a parietal contribution to episodic memory for spatial locations. Importantly, we could decode whether a room was visited in real life without the need of explicit judgments about the rooms. This suggests that recognition is an automatic response that can be decoded from fMRI data, thus potentially supporting forensic applications of concealed information tests for crime scene recognition. [ABSTRACT FROM AUTHOR]

When free-viewing scenes, participants tend to preferentially fixate social elements (e.g., people). In the present study, we tested whether this bias would be disrupted by increasing the demands of a secondary dual-task: holding a set of (one or six) spatial locations in memory, presented either simultaneously or sequentially. Following a retention interval, participants judged whether a test location was present in the to-be-remembered stimuli. During the retention interval participants free-viewed scenes containing a social element (a person) and a non-social element (an object) that served as regions of interest. In order to assess the impact of physical salience, the non-social element was presented in both an unaltered baseline version, and in a version where its salience was artificially increased. The results showed that the preference to look at social elements decreased when the demands of the spatial memory task were increased from one to six locations, regardless of presentation mode (simultaneous or sequential). The high-load condition also resulted in more central fixations and reduced exploration of the scene. The results indicate that the social prioritisation effect, and scene viewing more generally, can be affected by a concurrent memory load. [ABSTRACT FROM AUTHOR]

Background: Cognitive training and physical exercise show positive effects on cognitive decline in subjects with mild cognitive impairment (MCI). Multimodal interventions for MCI patients, combining physical and cognitive training in a social context seem to slow down cognitive decline. Objective: Based on a previous study, a new mobile gamification tool (go4cognition; https://www.ontaris.de/go4cognition) has been developed to train cognitive and physical functions simultaneously in a group setting. It involves tasks targeting various cognitive functions (short-term memory, working memory, executive functions). The computer-based setup allows for individual performance analysis. This study evaluated the effects of this tool. Methods: 30 participants with MCI, as defined by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cut-off-score, aged between 66 and 89 years, trained for one hour two days a week for twelve weeks. Additionally, standard neuropsychological assessment of memory and attention was carried out before and after the intervention. Results: The go4cognition device is highly effective in improving various cognitive functions. A significant improvement in the CERAD total score resulting in re-classification of 70% of former MCI patients into non-MCI patients was found. Additionally, an improvement of verbal fluency, verbal memory, spatial memory, and attention was observed. Furthermore, the CERAD total score was significantly correlated with performance in the go4cognition tool. Conclusions: The results of the intervention support the idea of the effectiveness of a combined cognitive and motor intervention by incorporating neuropsychological paradigms in a group setting and suggest a close relation between combined cognitive and physical exercise and cognitive performance. [ABSTRACT FROM AUTHOR]

In this paper, a reaction-diffusion population model with Dirichlet boundary condition and a directed movement oriented by a temporally distributed delay is proposed to describe the lasting memory of animals moving over space. The temporal kernel of the memory is taken as Gamma distribution function, among which there are two biologically meaningful cases: one is the weak kernel which implies that animals can immediately acquire knowledge and memory decays over time, the other is the strong kernel by which we assume that animals' memory undergoes learning and memory decay stages. It is shown that the population stabilizes to a positive steady state and aggregates in the interior of the territory when the delay kernel is the weak type. In the strong kernel case, oscillatory patterns can first arise via a Hopf bifurcation with a small memory delay and then vanish when the system undergoes a Hopf bifurcation with a large memory delay, which implies that stability switch occurs and spatial-temporal patterns emerge for intermediate value of delays. [ABSTRACT FROM AUTHOR]

Several studies report spatial memory decline in old age. However, few studies have examined whether old adults are specifically impaired in allocentric memory tasks (testing for object-to-object spatial location memory). Thus, the present study examined the effects of age on allocentric spatial memory using a novel landmark memory task. Young (18–25 years old) and old (65 years and older) participants watched 10 short videos that displayed 180-degree viewpoints of distinct real-world locations with landmark cues. After watching each video, participants saw a snapshot from the video and were asked whether a landmark cue previously viewed in the video was to the left or right of the snapshot view. Young adults outperformed old adults on the task. This age-related decline in spatial performance was similar for men and women. These findings support that spatial ability in an allocentric task is sensitive to age-related cognitive decline in men and women. [ABSTRACT FROM AUTHOR]

Background: Stress is a recognized risk factor for cognitive decline, which triggers neuroinflammation involving microglial activation. However, the specific mechanism for microglial activation under stress and affects learning and memory remains unclear. Methods: The chronic stress mouse model was utilized to explore the relationship between microglial activation and spatial memory impairment. The effect of hippocampal hyperglycemia on microglial activation was evaluated through hippocampal glucose-infusion and the incubation of BV2 cells with high glucose. The gain-and loss-of-function experiments were conducted to investigate the role of GLUT1 in microglial proinflammatory activation. An adeno-associated virus (AAV) was employed to specifically knockdown of GLUT1 in hippocampal microglia to assess its impact on stressed-mice. Results: Herein, we found that chronic stress induced remarkable hippocampal microglial proinflammatory activation and neuroinflammation, which were involved in the development of stress-related spatial learning and memory impairment. Mechanistically, elevated hippocampal glucose level post-stress was revealed to be a key regulator of proinflammatory microglial activation via specifically increasing the expression of microglial GLUT1. GLUT1 overexpression promoted microglial proinflammatory phenotype while inhibiting GLUT1 function mitigated this effect under high glucose. Furthermore, specific downregulation of hippocampal microglial GLUT1 in stressed-mice relieved microglial proinflammatory activation, neuroinflammation, and spatial learning and memory injury. Finally, the NF-κB signaling pathway was demonstrated to be involved in the regulatory effect of GLUT1 on microglia. Conclusions: We demonstrate that elevated glucose and GLUT1 expression induce microglia proinflammatory activation, contributing to stress-associated spatial memory dysfunction. These findings highlight significant interplay between metabolism and inflammation, presenting a possible therapeutic target for stress-related cognitive disorders. [ABSTRACT FROM AUTHOR]

Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay - a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time. [ABSTRACT FROM AUTHOR]

Stress-induced illnesses, like major depression, are among the leading causes of disability across the world. Consequently, there is a dire need for the validation of translationally-suited animal models incorporating social stress to uncover the etiology of depression. Prairie voles (Microtus ochrogaster) are more translationally relevant than many other rodent models as they display monogamous social and bi-parental behaviors. Therefore, we evaluated whether a novel social defeat stress (SDS) model in male prairie voles induces depression-relevant behavioral outcomes. Adult sexually-naïve male prairie voles experienced SDS bouts from a conspecific pair-bonded male aggressor, 10 min per day for 10 consecutive days. Non-stressed controls (same-sex siblings) were housed in similar conditions but never experienced physical stress. Twenty-four h later, voles were evaluated in social interaction, sucrose preference, and Morris water maze tests – behavioral endpoints validated to assess social withdrawal, anhedonia-related behavior, and spatial memory performance, respectively. SDS-exposed voles displayed lower sociability and body weight, decreased preference for a sucrose solution, and impairment of spatial memory retrieval. Importantly, no differences in general locomotor activity were observed as a function of SDS exposure. This study does not include female voles in the experimental design. We found that repeated SDS exposure, in male prairie voles, results in a depression-relevant phenotype resembling an anhedonia-like outcome (per reductions in sucrose preference) along with social withdrawal and spatial memory impairment – highlighting that the prairie vole is a valuable model with potential to study the neurobiology of social stress-induced depression-related outcomes. • Social defeat stress decreases social behavior in adult male prairie voles • Social defeat stress decreases sucrose preference in adult male prairie voles • Social defeat stress impairs spatial memory in adult male prairie voles • Vole social defeat stress displays strong face validity as a model for the study of depression-related phenotypes [ABSTRACT FROM AUTHOR]

Background: The cholinergic neuronal loss in the basal forebrain and increasing brain oxidative stress are one of the main features of the brain suffering from Alzheimer's disease. Marrubium vulgare (M. vulgare), commonly known as 'white horehound,' possesses a variety of valuable properties, such as antioxidative, anti-inflammatory, and antidiabetic activities. Moreover, it possesses neuromodulatory properties that could potentially impact short-term memory functions. Objective: The present study was undertaken to investigate the preventive effects of water M. vulgare extract on working memory, cholinergic neurotransmission, and oxidative stress in rats with scopolamine (Sco)-induced dementia. Methods: Male Wistar rats (200–250 g) were divided into four experimental groups. The plant extract was administered orally for 21 days, and Sco (2 mg/kg) was administered intraperitoneally for 11 consecutive days. The behavioral performance of the animals was evaluated by the T-maze test. The effect of the extract on acetylcholinesterase (AChE) activity and antioxidant status in cortex and hippocampus were also monitored. Results: Our experimental data revealed that treatment with M. vulgare significantly increased the percentage of correct choices of rats with Sco-induced dementia in the T maze test (by 38%, p < 0.05). Additionally, it reduced AChE activity in the hippocampus (by 20%, p < 0.05) and alleviated oxidative stress induced by Sco, particularly in the cortex. Conclusions: M. vulgare water extract demonstrated working memory preserving effect in rats with Sco-induced dementia, AChE inhibitory activity and in vivo antioxidant potential, and deserve further attention. [ABSTRACT FROM AUTHOR]

Adenosinergic modulation in the PFC is recognized for its involvement in various behavioral aspects including sleep homoeostasis, decision-making, spatial working memory and anxiety. While the principal cells of layer 6 (L6) exhibit a significant morphological diversity, the detailed cell-specific regulatory mechanisms of adenosine in L6 remain unexplored. Here, we quantitatively analyzed the morphological and electrophysiological parameters of L6 neurons in the rat medial prefrontal cortex (mPFC) using whole-cell recordings combined with morphological reconstructions. We were able to identify two differentmorphological categories of excitatory neurons in the mPFC of both juvenile and young adult rats with both sexes. These categories were characterized by a leading dendrite that was oriented either upright (toward the pial surface) or inverted (toward the white matter). These two excitatory neuron subtypes exhibited different electrophysiological and synaptic properties. Adenosine at a concentration of 30 µM indiscriminately suppressed connections with either an upright or an inverted presynaptic excitatory neuron. However, using lower concentrations of adenosine (10 µM) revealed that synapses originating fromL6 upright neurons have a higher sensitivity to adenosine-induced inhibition of synaptic release. Adenosine receptor activation causes a reduction in the probability of presynaptic neurotransmitter release that could be abolished by specifically blocking A1 adenosine receptors (A1ARs) using 8-cyclopentyltheophylline (CPT). Our results demonstrate a differential expression level of A1ARs at presynaptic sites of two functionally and morphologically distinct subpopulations of L6 principal neurons, suggesting the intricate functional role of adenosine in neuronal signaling in the brain. [ABSTRACT FROM AUTHOR]

Amniotes feature two principal visual processing systems: the tectofugal and thalamofugal pathways. In most mammals, the thalamofugal pathway predominates, routing retinal afferents through the dorsolateral geniculate complex to the visual cortex. In most birds, the thalamofugal pathway often plays the lesser role with retinal afferents projecting to the principal optic thalami, a complex of several nuclei that resides in the dorsal thalamus. This thalamic complex sends projections to a forebrain structure called the Wulst, the terminus of the thalamofugal visual system. The thalamofugal pathway in birds serves many functions such as pattern discrimination, spatial memory, and navigation/migration. A comprehensive analysis of avian species has unveiled diverse subdivisions within the thalamic and forebrain structures, contingent on species, age, and techniques utilized. In this study, we documented the thalamofugal system in three dimensions by integrating histological and contrast-enhanced computed tomography imaging of the avian brain. Sections of two-week-old chick brains were cut in either coronal, sagittal, or horizontal planes and stained with Nissl and either Gallyas silver or Luxol Fast Blue. The thalamic principal optic complex and pallial Wulst were subdivided on the basis of cell and fiber density. Additionally, we utilized the technique of diffusible iodine-based contrast-enhanced computed tomography (diceCT) on a 5-week-old chick brain, and right eyeball. By merging diceCT data, stained histological sections, and information from the existing literature, a comprehensive three-dimensional model of the avian thalamofugal pathway was constructed. The use of a 3D model provides a clearer understanding of the structural and spatial organization of the thalamofugal system. The ability to integrate histochemical sections with diceCT 3D modeling is critical to better understanding the anatomical and physiologic organization of complex pathways such as the thalamofugal visual system. [ABSTRACT FROM AUTHOR]

The cerebellum is involved in higher order cognitive function and is susceptible to agerelated atrophy. However, limited evidence has directly examined the cerebellum's role in cognitive aging. To interrogate potential substrates of the relationship between cerebellar structure and memory in aging, here we target the Purkinje cells (PCs). The sole output neurons of the cerebellum, PC loss and/or degeneration underlie a variety of behavioral abnormalities. Using a rat model of normal cognitive aging, we immunostained sections through the cerebellum for the PC-specific protein, calbindin-D28k. Although morphometric quantification revealed no significant difference in total PC number as a function of age or cognitive status, regional cell number was a more robust correlate of memory performance in the young cerebellum than in aged animals. Parallel biochemical analysis of PC-specific protein levels in whole cerebellum additionally revealed that calbindin-D28k and Purkinje cell protein-2 (pcp-2) levels were lower selectively in aged rats with spatial memory impairment compared to both young animals and aged rats with intact memory. These results suggest that cognitive aging is associated with cerebellum vulnerability, potentially reflecting disruption of the cerebellum--medial temporal lobe network. [ABSTRACT FROM AUTHOR]

Does the mind rely on similar systems of spatial representation for both perception and action? Here, we assessed the format of location representations in two simple spatial localization tasks. In one task, participants simply remembered the location of an item based solely on visual input. In another, participants remembered the location of a point in space based solely on kinesthetic input. Participants' recall errors were more consistent with the use of polar coordinates than Cartesian coordinates in both tasks. Moreover, measures of spatial bias and performance were correlated across modalities. In a subsequent study, we tested the flexibility with which people use polar coordinates to represent space; we show that the format in which the information is presented to participants influences how that information is encoded and the errors that are made as a result. We suggest that polar coordinates may be a common means of representing location information across visual and motor modalities, but that these representations are also flexible in form. [ABSTRACT FROM AUTHOR]

Studies using a relatedness judgement task have found differences between prime-target word pairs that vary in the degree of semantic relatedness. However, the influence of working memory load on semantic processing in this task and the role of the type of working memory task have not yet been investigated. The present study therefore investigated for the first time the effect of working memory load (low vs. high) and working memory type (verbal vs. spatial) on semantic relatedness judgements. Semantically strongly related (e.g., hip – KNEE), weakly related (e.g., muscle – KNEE) and unrelated (e.g., office – KNEE) Polish word pairs were presented in an experiment involving a dual working memory and semantic relatedness task. The data revealed that, relative to semantically unrelated word pairs, responses were faster for strongly related pairs but slower for weakly related pairs. Importantly, the verbal working memory task decreased facilitation for strongly related pairs and increased inhibition for weakly related pairs relative to the spatial working memory task. Furthermore, working memory load impacted only weakly related pairs in the verbal but not in the spatial working memory task. These results show that working memory type and load influence semantic relatedness judgements, but the direction and size of the impact depend on the strength of semantic relations. [ABSTRACT FROM AUTHOR]

Background: Depression and memory disorders are known to be associated with increased oxidative stress. There is evidence suggesting that Quercus brantii (Q. brantii) possesses antioxidant properties. Objectives: This study aims to investigate the impact of Q. brantii hydro-alcoholic extract and oil on cognitive dysfunction in a postpartum depression (PPD) model and on oxidant/antioxidant activity in the hippocampus of adult female rats. Methods: Forty-two female Wistar rats (200 - 250 g) were randomly divided into six groups. PPD was induced by chronic intraperitoneal administration (5 days) of progesterone at a dose of 5 mg/kg, and three days after discontinuation, depressive behavior was assessed using a forced swimming test. Simultaneously, Quercus brantii hydro-alcoholic extract (100 mg/kg) and oil (45%) were administered. Spatial memory and locomotor activity were evaluated 24 hours after training using the Morris water maze and open field tests, respectively. The hippocampus tissue of all rats was used to evaluate oxidant-antioxidant factors, Vitamin D, and corticosterone levels. Results:Quercus brantii extract significantly reduced depression (P < 0.05). Treatment with Q. brantii extract and oil improved spatial memory and learning (P < 0.05). The Q. brantii extract increased levels of SOD, GSH, catalase, and vitamin D while decreasing MDA levels; additionally, Q. brantii oil increased SOD and vitamin D levels and decreased MDA levels in the brain (P < 0.05). Conclusions:Quercus brantii extract and oil appear to have beneficial effects on learning and memory impairment in a PPDinduced model, which may be associated with their biochemical effects on the brain. [ABSTRACT FROM AUTHOR]

Aiming at fast and accurate spatiotemporal prediction of interfacial flow fields, a novel deep learning model combining Convolutional AutoEncoder (CAE) and long short-term memory with spatial and temporal attention (LSTM-STA) is proposed and named as CAE-LSTM-STA (hybrid model of CAE and LSTM-STA) in this article. To enable a fast calculation process, CAE is first utilized to compress the high-dimensional snapshots of flow fields into the low-dimensional latent space by its encoder. Then, the latent space serves as the input feature for LSTM-STA to temporally evolve the state of the low-dimensional latent space. Finally, the low-dimensional latent space at future time steps is fed back into the decoder of CAE to derive the full-order snapshots of the flow fields. The prediction performance of the proposed model is evaluated via two representative benchmark cases, including the dam break case and the rising bubble case. The capability of CAE in dimension reduction is found to be much better than that of the widely used Proper Orthogonal Decomposition, while LSTM-STA is observed that outperforms the original LSTM in multivariant temporal prediction. These promising results indicate that the proposed CAE-LSTM-STA model is able to effectively capture and advance the spatiotemporal characteristics of the interfacial flow fields, therefore making it an advanced surrogate model for fast and precise generation of the temporally continuous interfacial flow fields. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with development of tauopathies that contribute to cognitive decline. Without functional leptin receptors, male obese Zucker rats (OZRs) develop MetS, and they have increased phosphorylated tau (ptau) with impaired cognitive function. In addition to regulating energy balance, leptin enhances activation of the hippocampus, which is essential for spatial learning and memory. Whether spatial learning and memory are always impaired in OZRs or develop with MetS is unknown. We hypothesized that male OZRs develop MetS traits that promote regional increases in ptau and functional deficits associated with those brain regions. In the medulla and cortex, tau-pSer199,202 and tau-pSer396 were comparable in juvenile (7–8 wk old) lean Zucker rats (LZRs) and OZRs but increased in 18- to 19-wk-old OZRs. Elevated tau-pSer396 was concentrated in the dorsal vagal complex of the medulla, and by this age OZRs had hypertension with increased arterial pressure variability. In the hippocampus, tau-pSer199,202 and tau-pSer396 were still comparable in 18- to 19-wk-old OZRs and LZRs but elevated in 28- to 29-wk-old OZRs, with emergence of deficits in Morris water maze performance. Comparable escape latencies observed during acquisition in 18- to 19-wk-old OZRs and LZRs were increased in 28- to 29-wk-old OZRs, with greater use of nonspatial search strategies. Increased ptau developed with changes in the insulin/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in the hippocampus and cortex but not medulla, suggesting different underlying mechanisms. These data demonstrate that leptin is not required for spatial learning and memory in male OZRs. Furthermore, early development of MetS-associated autonomic dysfunction by the medulla may be predictive of later hippocampal dysfunction and cognitive impairment. NEW & NOTEWORTHY: Male obese Zucker rats (OZRs) lack functional leptin receptors and develop metabolic syndrome (MetS). At 16–19 wk, OZRs are insulin resistant, with increased ptau in dorsal medulla and impaired autonomic regulation of AP. At 28–29 wk OZRs develop increased ptau in hippocampus with deficits in spatial learning and memory. Juvenile OZRs lack elevated ptau and these deficits, demonstrating that leptin is not essential for normal function. Elevated ptau and deficits emerge before the onset of diabetes in insulin-resistant OZRs. [ABSTRACT FROM AUTHOR]

Boundaries define space, impacting spatial memory and neural representations. Unlike rodents, impact in humans is often tested using desktop virtual-reality (VR). This lacks self-motion cues, diminishing path-integration input. We replicated a desktop-VR study testing boundary impact on spatial memory for object locations using a physical, desktop-VR, and head-mounted-display-VR environment. Performance was measured by comparing participant responses to seven spatial distribution models using geometric or walking-path metrics. A weighted-linear combination of geometric models and a "place-cell-firing" model performed best, with identical fits across environments. Spatial representation appears differentially influenced by different boundary changes, but similarly across virtual and physical environments. [ABSTRACT FROM AUTHOR]

Being able to represent and remember verbally-encoded information about spatial environments from different perspectives is important for numerous daily activities. The present study examined how frequently individuals spontaneously engage in visual mental imagery and verbal rehearsal strategies in memory recall of spatial descriptions, and whether using certain strategies is associated with better recall performance. Memory recall for route (person-centred) and survey (object-centred) spatial descriptions was examined in a sample of 105 neurotypical individuals, who also reported to what extent they used route- and survey-based mental imagery and verbal rehearsal strategies in each description. Results showed that participants favoured a path visualisation strategy to recall the route description and a map visualisation strategy to recall the survey description. Regression models further showed that employing both imagery and verbal strategies was associated with better recall for both route and survey descriptions, although imagery strategies held a higher predictive power. The present findings highlight the fact that the spontaneous use of internal strategies in the form of visual imagery and verbal rehearsal is ubiquitous when recalling spatial descriptions and a core part of efficient spatial memory functioning. [ABSTRACT FROM AUTHOR]

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse's hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders. [ABSTRACT FROM AUTHOR]

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer's disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5–20 mg/kg/day, oral) for 3 weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1β. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain. [ABSTRACT FROM AUTHOR]

Humans can extract high‐level spatial features from visual signals, but spatial representations in the brain are complex and remain unclear. The unsupervised capsule neural network (U‐CapsNet) is sensitive to the spatial location and relationship of the object, contains a special recurrent mechanism and uses a self‐supervised generation strategy to represent images, which is similar to the computational principle in the human brain. Therefore, we hypothesized that U‐CapsNet can help us understand how the human brain processes spatial information. First, brain activities were studied using functional magnetic resonance imaging during spatial working memory in which participants had to remember the locations of circles for a short time. Then, U‐CapsNet served as a computational model of the brain to perform tasks that are identical to those performed by humans. Finally, the representational models were used to compare the U‐CapsNet with the brain. The results showed that some human‐defined spatial features naturally emerged in the latent space of U‐CapsNet. Moreover, representations in U‐CapsNet captured the response structure of two types of brain regions during different activity patterns, as well as important factors associated with human behavior. Together, our study not only provides a computationally feasible framework for modeling how the human brain encodes spatial features but also provides insights into the representational format and goals of the human brain. [ABSTRACT FROM AUTHOR]