Object Location Memory Research Articles

Minocycline prevents early age-related cognitive decline in a mouse model of intellectual disability caused by ZBTB18/RP58 haploinsufficiency

Haploinsufficiency of the transcriptional repressor ZBTB18/RP58 is associated with intellectual disability. However, the mechanisms causing this disability are unknown, and preventative measures and treatments are not available. Here, we assessed multiple behaviors in Zbtb18/Rp58 heterozygous-knockout mice, and examined local field potentials, DNA fragmentation, mitochondrial morphology, and performed histochemical and transcriptome analyses in the hippocampus to evaluate chronic inflammation. In wild-type mice, object location memory was present at a similar level at 2 and 4–5 months of age, and became impaired at 12–18 months. In contrast, Zbtb18/Rp58 heterozygous-knockout mice displayed early onset impairments in object location memory by 4–5 months of age. These mice also exhibited earlier accumulation of DNA and mitochondrial damage, and activated microglia in the dentate gyrus, which are associated with defective DNA repair. Notably, chronic minocycline therapy, which has neuroprotective and anti-inflammatory effects, attenuated age-related phenotypes, including accumulation of DNA damage, increased microglial activation, and impairment of object location memory. Our results suggest that Zbtb18/Rp58 activity is required for DNA repair and its reduction results in DNA and mitochondrial damage, increased activation of microglia, and inflammation, leading to accelerated declines in cognitive functions. Minocycline has potential as a therapeutic agent for the treatment of ZBTB18/RP58 haploinsufficiency-associated cognitive dysfunction.

Crucial role of Snf7-3 in synaptic function and cognitive behavior revealed by conventional and conditional knockout mouse models

Snf7-3 is a crucial component of the endosomal sorting complexes required for transport (ESCRT) pathway, playing a vital role in endolysosomal functions. To elucidate the role of Snf7-3 in vivo, we developed conventional-like and conditional Snf7-3 knockout (KO) mouse models using a “Knockout-first” strategy. Conventional-like Snf7-3 KO mice showed significantly reduced Snf7-3 mRNA expression, and older mice (25–40 weeks) exhibited impaired social recognition and increased miniature excitatory postsynaptic currents (mEPSCs). Similarly, conditional KO mice aged 8–24 weeks, with Snf7-3 specifically deleted in forebrain excitatory neurons, displayed impaired object location memory and elevated mEPSC frequency. Consistently, Snf7-3 knockdown in cultured mouse hippocampal neurons led to increased densities of pre- and postsynaptic puncta, supporting the observed increase in mEPSC frequency. In addition, enhanced dendritic complexity was observed in the medial prefrontal cortex of these mice, indicating early synaptic disturbances. Our findings underscore the critical role of Snf7-3 in maintaining normal cognitive functions and social behaviors. The observed synaptic and behavioral deficits in both conventional-like and conditional KO mice highlight the importance of Snf7-3 in specific neuronal populations, suggesting that early synaptic changes could precede more pronounced cognitive impairments.

Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory.

Memory formation is contingent on molecular and structural changes in neurons in response to learning stimuli-a process known as neuronal plasticity. The initiation step of mRNA translation is a gatekeeper of long-term memory by controlling the production of plasticity-related proteins in the brain. The mechanistic target of rapamycin complex 1 (mTORC1) controls mRNA translation, mainly through phosphorylation of the eukaryotic initiation factor 4E (eIF4E)-binding proteins (4E-BPs) and ribosomal protein S6 kinases (S6Ks). mTORC1 signaling decreases throughout brain development, starting from the early postnatal period. Here, we discovered that in mice, the age-dependent decrease in mTORC1 signaling occurs selectively in excitatory but not inhibitory neurons. Using a gene conditional knockout (cKO) strategy, we demonstrate that either up- or downregulating the mTORC1-4E-BP2 axis in GAD65 inhibitory interneurons, but not excitatory neurons, results in long-term object recognition and object location memory deficits. Our data indicate that the mTORC1 pathway in inhibitory but not excitatory neurons plays a key role in memory formation.

Natural- and redirected walking in virtual reality: Spatial performance and user experience

AbstractImmersive virtual reality offers a range of unique possibilities. One of these is the realistic exploration of virtual worlds using natural walking. This however becomes difficult when the size of the virtual world exceeds that of the available physical space. Redirected walking in virtual reality presents a novel solution to this problem by typically making its users think to be walking in a straight line while they are in fact walking in a curve, thus allowing them to physically walk long distances in confined physical spaces. Yet, few studies have examined the effects of redirected walking on variables such as spatial memory, navigation and user experience as compared to other immersive and non-immersive locomotion methods. In a maze task we examined 1) redirected- and 2) natural walking in immersive virtual reality conditions, and 3) artificial locomotion on a non-immersive desktop monitor. Walked path lengths became shorter and distance estimates, object location memory and user experience improved using natural walking compared to a monitor condition. However, redirected walking yielded similar performance to natural walking while requiring less physical space, opening up possibilities for more pervasive use of real locomotion in virtual environments.

FDA-approved cannabidiol [Epidiolex®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis

BackgroundChronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.MethodsSix months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.ResultsGWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.ConclusionsThe use of an FDA-approved CBD (Epidiolex®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.

Differential role of NMDA receptors in hippocampal-dependent spatial memory and plasticity in juvenile male and female rats.

Early life, or juvenility, stands out as the most pivotal phase in neurodevelopment due to its profound impact over the long-term cognition. During this period, significant changes are made in the brain's connections both within and between different areas, particularly in tandem with the development of more intricate behaviors. The hippocampus is among the brain regions that undergo significant postnatal remodeling, including dendritic arborization, synaptogenesis, the formation of complex spines and neuron proliferation. Given the crucial role of the hippocampus in spatial memory processing, it has been observed that spatial memory abilities continue to develop as the hippocampus matures, particularly before puberty. The N-methyl-d-aspartate (NMDA) type of glutamate receptor channel is crucial for the induction of activity-dependent synaptic plasticity and spatial memory formation in both rodents and humans. Although extensive evidence shows the role of NMDA receptors (NMDAr) in spatial memory and synaptic plasticity, the studies addressing the role of NMDAr in spatial memory of juveniles are sparse and mostly limited to adult males. In the present study, we, therefore, aimed to investigate the effects of systemic NMDAr blockade by the MK-801 on spatial memory (novel object location memory, OLM) and hippocampal plasticity in the form of long-term potentiation (LTP) of both male and female juvenile rats. Our results show the sex-dimorphic role of NMDAr in spatial memory and plasticity during juvenility, as systemic NMDAr blockade impairs the OLM and LTP in juvenile males without an effect on juvenile females. Taken together, our results demonstrate that spatial memory and hippocampal plasticity are NMDAr-dependent in juvenile males and NMDAr-independent in juvenile females. These sex-specific differences in the mechanisms of spatial memory and plasticity may imply gender-specific treatment for spatial memory disorders even in children.

The weekend warrior effect: Consistent intermittent exercise induces persistent cognitive benefits

Exercise provides a range of cognitive benefits, including improved memory performance. Previously, we demonstrated that 14 days of continuous voluntary wheel-running exercise enables learning in a hippocampus-dependent Object Location Memory (OLM) task under insufficient, subthreshold training conditions in adult mice. Whether similar exercise benefits can be obtained from consistent intermittent exercise as continuous exercise is unknown. Here, we examine whether intermittent exercise (the weekend warrior effect: 2 days of exercise a week for 7 weeks) displays similar or distinct cognitive benefits as previously examined with 14 days of continuous exercise. We find that both continuous and intermittent exercise parameters similarly enable hippocampus-dependent OLM compared to the 2-day exercise control group. Mice receiving intermittent exercise maintained cognitive benefits following a 7-day sedentary delay, whereas mice that underwent 14 continuous days of exercise showed diminished cognitive benefits as previously reported. Further, compared to continuous exercise, intermittent exercise mice exhibited persistently elevated levels of the genes Acvr1c and Bdnf which we know to be critically involved in hippocampus-dependent long-term memory in the dorsal hippocampus. Together findings suggest that consistent intermittent exercise persistently enables hippocampal-dependent long-term memory. Understanding the optimal parameters for persistent cognitive function and the mechanisms mediating persistent effects will aid in therapeutic pursuits investigating the mitigation of cognitive ailments.

Association between adolescent alcohol use and cognitive function in young adulthood: A co-twin comparison study.

Studies on adolescent alcohol use and cognition are often unable to separate the potential causal effects of alcohol use on cognition from shared etiological influences, including genetic influences or other substance use comorbidities also known to be associated with cognition, such as nicotine use. The present study aimed to fill this gap and clarify the relationship between adolescent alcohol use and young adult cognition by accounting for both measured and unmeasured confounders. A random effects model accounting for nesting in families was used to control for measured confounders. Next, co-twin comparisons were conducted within the full sample and in monozygotic twin pairs (MZ) to control for unmeasured genetic and environmental confounders shared by co-twins. Participants were 812 individuals (58.6% female, 361 complete pairs, 146 MZ pairs) from the longitudinal FinnTwin12 study in Finland. Adolescent alcohol use was indexed with measures of frequency of use and intoxication averaged across ages 14 and 17. Cognitive outcomes were measured at average age 22 and included Trail Making Test, California Stroop test, Wechsler Adult Intelligence subtests (Vocabulary, Block Design, Digit Symbol), Digit Span subtest of Wechsler Memory Scale, Mental Rotation Test and Object Location Memory test. Covariates included sex, parental education, general cognitive ability, current alcohol use and nicotine use. Greater frequency of alcohol use and frequency of intoxication across adolescence was associated with decreased vocabulary scores in the co-twin control [freq: stnd beta = -0.12, 95% confidence interval (CI) = -0.234, -0.013] and MZ only co-twin control models (freq: stnd beta = -0.305, 95% CI = -0.523, -0.087; intox: stnd beta = -0.301, 95% CI = -0.528, -0.074). In Finland, there appears to be little evidence that adolescent alcohol use causes cognitive deficits in young adulthood, except modest evidence for association of higher adolescent alcohol use with lower young adult vocabulary scores.

An immersive virtual reality-based object-location memory task reveals spatial long-term memory alterations in Long-COVID

Object-location memory (OLM) is a type of declarative memory for spatial information and consists of the individual's ability to establish accurate associations between objects and their spatial locations. Long-COVID describes the long-term effects of the COVID-19 disease. Long-COVID patients show medial temporal lobe dysfunction and neuropsychological alterations affecting memory. This study aimed to assess OLM in a group of Long-COVID patients, n=66, and a Control group of healthy individuals with similar age and sex composition, n=21, using an immersive virtual reality (iVR)-based OLM task. We also explored associations between the performance in the iVR-based OLM task and general cognitive function (MoCA), and both verbal (VSTM) and visuospatial (SSTM) span. The Long-COVID group showed fewer correct responses, made more task attempts, and invested more time in the iVR-based OLM task than the Control group. Delayed memory was more severely altered than immediate memory in Long-COVID participants. Better MoCA scores of the Long-COVID group were strongly associated with shorter times to complete the immediate recall of the iVR-based OLM task. Besides, the months elapsed since the COVID-19 infection were slightly associated with fewer correct responses in the immediate and 24-hour recalls. These results corroborate previous findings of memory alterations in the Long-COVID syndrome using an iVR-based OLM task, adding new evidence on spatial memory and long-term memory in this population. Implementing spatial iVR tasks to clinical research may improve our understanding of neuropsychological disorders.

How people with brain injury run and evaluate a SLAM-based smartphone augmented reality application to assess object-location memory.

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.

Paradoxical boosting of weak and strong spatial memories by hippocampal dopamine uncaging.

The ability to remember changes in the surroundings is fundamental for daily life. It has been proposed that novel events producing dopamine release in the hippocampal CA1 region could modulate spatial memory formation. However, the role of hippocampal dopamine increase on weak or strong spatial memories remains unclear. We show that male mice exploring two objects located in a familiar environment for 5 minutes created a short-term memory (weak) that cannot be retrieved one day later, whereas 10 minutes exploration created a long-term memory (strong) that can be retrieved one day later. Remarkably, hippocampal dopamine elevation during the encoding of weak object location memories (OLMs) allowed their retrieval one day later but dopamine elevation during the encoding of strong OLMs promoted the preference for a familiar object location over a novel object location after 24 hours. Moreover, dopamine uncaging after the encoding of OLMs did not have effect on weak memories whereas on strong memories diminished the exploration of the novel object location. Additionally, hippocampal dopamine elevation during the retrieval of OLMs did not allow the recovery of weak memories and did not affect the retrieval of strong memory traces. Finally, dopamine elevation increased hippocampal theta oscillations, indicating that dopamine promotes the recurrent activation of specific groups of neurons. Our experiments demonstrate that hippocampal dopaminergic modulation during the encoding of OLMs depends on memory strength indicating that hyperdopaminergic levels that enhance weak experiences could compromise the normal storage of strong memories.Significance statement Increased levels of dopamine have been related to cognitive enhancement. Hippocampal dopamine elevation caused by novelty exposure has been proposed as a strategy to enhance memory based on the observation that surprising events create flashbulb memories that are remembered for long time. However, hyperdopaminergic levels could also underlie maladaptive memories, such as non-desired preservation of traumatic experiences. Our experiments show that dopamine elevation in the dorsal hippocampus during the encoding of spatial memories has paradoxical effects, while the enhancement of weak memories allows their retrieval, the dopaminergic modulation of strong memories limits the ability to modify preexisting spatial memories by changes in the environment. We conclude that cognitive enhancement through dopamine boosting must consider diverse aspects of memory formation.

No Object-Location Memory Improvement through Focal Transcranial Direct Current Stimulation over the Right Temporoparietal Cortex.

Remembering objects and their associated location (object-location memory; OLM), is a fundamental cognitive function, mediated by cortical and subcortical brain regions. Previously, the combination of OLM training and transcranial direct current stimulation (tDCS) suggested beneficial effects, but the evidence remains heterogeneous. Here, we applied focal tDCS over the right temporoparietal cortex in 52 participants during a two-day OLM training, with anodal tDCS (2 mA, 20 min) or sham (40 s) on the first day. The focal stimulation did not enhance OLM performance on either training day (stimulation effect: -0.09, 95%CI: [-0.19; 0.02], p = 0.08). Higher electric field magnitudes in the target region were not associated with individual performance benefits. Participants with content-related learning strategies showed slightly superior performance compared to participants with position-related strategies. Additionally, training gains were associated with individual verbal learning skills. Consequently, the lack of behavioral benefits through focal tDCS might be due to the involvement of different cognitive processes and brain regions, reflected by participant's learning strategies. Future studies should evaluate whether other brain regions or memory-relevant networks may be involved in the modulation of object-location associations, investigating other target regions, and further exploring individualized stimulation parameters.

Semantic partitioning facilitates memory for object location through category-partition cueing

ABSTRACT In our lived environments, objects are often semantically organised (e.g., cookware and cutlery are placed close together in the kitchen). Across four experiments, we examined how semantic partitions (that group same-category objects in space) influenced memory for object locations. Participants learned the locations of items in a semantically partitioned display (where each partition contained objects from a single category) as well as a purely visually partitioned display (where each partition contained a scrambled assortment of objects from different categories). Semantic partitions significantly improved location memory accuracy compared to the scrambled display. However, when the correct partition was cued (highlighted) to participants during recall, performance on the semantically partitioned display was similar to the scrambled display. These results suggest that semantic partitions largely benefit memory for location by enhancing the ability to use the given category as a cue for a visually partitioned area (e.g., toys – top left). Our results demonstrate that semantically structured spaces help location memory across partitions, but not items within a partition, providing new insights into the interaction between meaning and memory.

Egocentric and Allocentric Spatial Memory for Body Parts: A Virtual Reality Study.

Extensive literature elucidated the mechanisms underlying the ability to memorize the positions of objects in space. However, less is known about the impact that objects' features have on spatial memory. The present study aims to investigate differences in egocentric and allocentric object-location memory between hand stimuli depicted in a first-person perspective (1PP) or in a third-person one (3PP). Fifty-two adults encoded spatial positions within a virtual museum environment featuring four square buildings. Each of these buildings featured eight paintings positioned along the walls, with two pictures displayed on each of the four walls. Thirty-two stimuli were employed, which represented pictures of the right hand performing various types of gestures. Half of the stimuli depicted the hand in the 1PP, while the other half depicted the hand in the 3PP. Both free and guided explorations served as encoding conditions. Immediately after that, participants underwent a two-step object-location memory task. Participants were provided with a map of the museum and asked to identify the correct building where the image was located (allocentric memory). Then, they were presented with a schematic representation of the exhibition room divided into four sections and instructed to select the section where they thought the picture was located (egocentric memory). Our findings indicate a memory performance boost associated with egocentric recall, regardless of the perspective of the bodily stimuli. The results are discussed considering the emerging literature on the mnemonic properties of body-related stimuli for spatial memory.

Canonical Wnt activator Chir99021 prevents epileptogenesis in the intrahippocampal kainate mouse model of temporal lobe epilepsy

The Wnt signaling pathway mediates the development of dentate granule cell neurons in the hippocampus. These neurons are central to the development of temporal lobe epilepsy and undergo structural and physiological remodeling during epileptogenesis, which results in the formation of epileptic circuits. The pathways responsible for granule cell remodeling during epileptogenesis have yet to be well defined, and represent therapeutic targets for the prevention of epilepsy. The current study explores Wnt signaling during epileptogenesis and for the first time describes the effect of Wnt activation using Wnt activator Chir99021 as a novel anti-epileptogenic therapeutic approach.Focal mesial temporal lobe epilepsy was induced by intrahippocampal kainate (IHK) injection in wild-type and POMC-eGFP transgenic mice. Wnt activator Chir99021 was administered daily, beginning 3 h after seizure induction, and continued up to 21-days. Immature granule cell morphology was quantified in the ipsilateral epileptogenic zone and the contralateral peri-ictal zone 14 days after IHK, targeting the end of the latent period. Bilateral hippocampal electrocorticographic recordings were performed for 28-days, 7-days beyond treatment cessation. Hippocampal behavioral tests were performed after completion of Chir99021 treatment.Consistent with previous studies, IHK resulted in the development of epilepsy after a 14 day latent period in this well-described mouse model. Activation of the canonical Wnt pathway with Chir99021 significantly reduced bilateral hippocampal seizure number and duration. Critically, this effect was retained after treatment cessation, suggesting a durable antiepileptogenic change in epileptic circuitry. Morphological analyses demonstrated that Wnt activation prevented pathological remodeling of the primary dendrite in both the epileptogenic zone and peri-ictal zone, changes in which may serve as a biomarker of epileptogenesis and anti-epileptogenic treatment response in pre-clinical studies. These findings were associated with improved object location memory with Chir99021 treatment after IHK.This study provides novel evidence that canonical Wnt activation prevents epileptogenesis in the IHK mouse model of mesial temporal lobe epilepsy, preventing pathological remodeling of dentate granule cells. Wnt signaling may therefore play a key role in mesial temporal lobe epileptogenesis, and Wnt modulation may represent a novel therapeutic strategy in the prevention of epilepsy.

An exploration of the influence of animal and object categories on recall of item location following an incidental learning task.

The current study explores the role of attention in location memory for animals and objects. Participants completed an incidental learning task where they rated animals and objects with regard to either their ease of collection to win a scavenger hunt (Experiments 1a and b) or their distance from the centre of the computer screen (Experiment 2). The images of animals and objects were pseudo-randomly positioned on the screen in both experiments. After completing the incidental learning task (and a reverse counting distractor task), participants were then given a surprise location memory recall task. In the location memory recall task, items were shown in the centre of the screen and participants used the mouse to indicate the position the item had been shown during the incidental encoding task. The results of both experiments show that location memory for objects was more accurate than for animals. While we cannot definitively identify the mechanism responsible for the difference in the location memory of objects and animals, we propose that differences in the influence of object-based attention at encoding affect location memory when tested at recall.

The role of the m6A/m demethylase FTO in memory is both task and sex-dependent in mice

Formation of long-term memories requires learning-induced changes in both transcription and translation. Epitranscriptomic modifications of RNA recently emerged as critical regulators of RNA dynamics, whereby adenosine methylation (m6A) regulates translation, mRNA stability, mRNA localization, and memory formation. Prior work demonstrated a pro-memory phenotype of m6A, as loss of m6A impairs and loss of the m6A/m demethylase FTO improves memory formation. Critically, these experiments focused exclusively on aversive memory tasks and were only performed in male mice. Here we show that the task type and sex of the animal alter effects of m6A on memory, whereby FTO-depletion impaired object location memory in male mice, in contrast to the previously reported beneficial effects of FTO depletion on aversive memory. Additionally, we show that female mice have no change in performance after FTO depletion, demonstrating that sex of the mouse is a critical variable for understanding how m6A contributes to memory formation. Our study provides the first evidence for FTO regulation of non-aversive spatial memory and sexspecific effects of m6A, suggesting that identification of differentially methylated targets in each sex and task will be critical for understanding how epitranscriptomic modifications regulate memory.

Semantic partitioning facilitates memory for object location through category-partition cueing

ABSTRACT In our lived environments, objects are often semantically organised (e.g., cookware and cutlery are placed close together in the kitchen). Across four experiments, we examined how semantic partitions (that group same-category objects in space) influenced memory for object locations. Participants learned the locations of items in a semantically partitioned display (where each partition contained objects from a single category) as well as a purely visually partitioned display (where each partition contained a scrambled assortment of objects from different categories). Semantic partitions significantly improved location memory accuracy compared to the scrambled display. However, when the correct partition was cued (highlighted) to participants during recall, performance on the semantically partitioned display was similar to the scrambled display. These results suggest that semantic partitions largely benefit memory for location by enhancing the ability to use the given category as a cue for a visually partitioned area (e.g., toys – top left). Our results demonstrate that semantically structured spaces help location memory across partitions, but not items within a partition, providing new insights into the interaction between meaning and memory.

Ripple-locked coactivity of stimulus-specific neurons and human associative memory

Associative memory enables the encoding and retrieval of relations between different stimuli. To better understand its neural basis, we investigated whether associative memory involves temporally correlated spiking of medial temporal lobe (MTL) neurons that exhibit stimulus-specific tuning. Using single-neuron recordings from patients with epilepsy performing an associative object–location memory task, we identified the object-specific and place-specific neurons that represented the separate elements of each memory. When patients encoded and retrieved particular memories, the relevant object-specific and place-specific neurons activated together during hippocampal ripples. This ripple-locked coactivity of stimulus-specific neurons emerged over time as the patients’ associative learning progressed. Between encoding and retrieval, the ripple-locked timing of coactivity shifted, suggesting flexibility in the interaction between MTL neurons and hippocampal ripples according to behavioral demands. Our results are consistent with a cellular account of associative memory, in which hippocampal ripples coordinate the activity of specialized cellular populations to facilitate links between stimuli.

Real and virtual environments have comparable spatial memory distortions after scale and geometric transformations

ABSTRACT 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.