Spatial Navigation Research Articles

Wide-angle simulated artificial vision enhances spatial navigation and object interaction in a naturalistic environment.

Vision restoration approaches, such as prosthetics and optogenetics, provide visual perception to blind individuals in clinical settings. Yet their effectiveness in daily life remains a challenge. Stereotyped quantitative tests used in clinical trials often fail to translate into practical, everyday applications. On the one hand, assessing real-life benefits during clinical trials is complicated by environmental complexity, reproducibility issues, and safety concerns. On the other hand, predicting behavioral benefits of restorative therapies in naturalistic environments may be a crucial step before starting clinical trials to minimize patient discomfort and unmet expectations.
Approach. To address this, we leverage advancements in virtual reality technology to conduct a fully immersive and ecologically valid task within a physical artificial street environment. As a case study, we assess the impact of the visual field size in simulated artificial vision for common outdoor tasks.
Main Results. We show that a wide visual angle (45°) enhances participants' ability to navigate and solve tasks more effectively, safely, and efficiently. Moreover, it promotes their learning and generalization capability. Concurrently, it changes the visual exploration behavior and facilitates a more accurate mental representation of the environment. Further increasing the visual angle beyond this value does not yield significant additional improvements in most metrics.
Significance. We present a methodology combining augmented reality with a naturalistic environment, enabling participants to perceive the world as patients with retinal implants would and to interact physically with it. Combining augmented reality in naturalistic environments is a valuable framework for low vision and vision restoration research.

The Wolf Spider Tigrosa helluo Uses Visual Associative and Beacon Landmarks During Water Maze Navigation Tasks

ABSTRACTWolf spiders can learn simple spatial navigation tasks. Previous studies have shown that the wolf spider Tigrosa helluo can use environmental edge features (reference frame landmarks) to learn the location of a dry target in flooded T‐mazes; however, the relative importance of different types or numbers of landmark cues to spatial learning remains unknown. We used a modified open arena water maze and recorded the ability of adult female T. helluo to find a target reward (a dark and dry cup) among cups that were identical to the target but flooded. We measured variation in spatial learning by measuring time to target with no landmark (control), with a beacon (a landmark that is part of the target), with an associative cue (a landmark associated with a specific navigational action), and with both a beacon and an associative cue (N = 92 subjects, n = 23 per landmark cue treatment). For each treatment, we tested females for five trials each on four consecutive days, with the last trial on the fourth day having an altered target location, totaling 19 training trials and one reversal trial (1840 trials). We found that spiders took significantly less time to find the target over subsequent trials within a day and learned more quickly when landmark cues were present, but we found no difference in the type or number of landmark features in the meantime to target entrance. After learning a target location, moving the landmark significantly increased the mean time to target entrance in the combined beacon and associative cue treatment relative to other treatments. Our results indicate that wolf spiders use visual beacons and associative cue landmarks alone or in combination and that performance improves across trials when landmarks are present and deteriorates more when multiple landmarks are moved.

Architectural styles of curiosity in global Wikipedia mobile app readership.

Intrinsically motivated information seeking is an expression of curiosity believed to be central to human nature. However, most curiosity research relies on small, Western convenience samples. Here, we analyze a naturalistic population of 482,760 readers using Wikipedia's mobile app in 14 languages from 50 countries or territories. By measuring the structure of knowledge networks constructed by readers weaving a thread through articles in Wikipedia, we replicate two styles of curiosity previously identified in laboratory studies: the nomadic "busybody" and the targeted "hunter." Further, we find evidence for another style-the "dancer"-which was previously predicted by a historico-philosophical examination of texts over two millennia and is characterized by creative modes of knowledge production. We identify associations, globally, between the structure of knowledge networks and population-level indicators of spatial navigation, education, mood, well-being, and inequality. These results advance our understanding of Wikipedia's global readership and demonstrate how cultural and geographical properties of the digital environment relate to different styles of curiosity.

A framework for a low-cost system of automated gate control in assays of spatial cognition in fishes.

Automation of experimental setups is a promising direction in behavioral research because it can facilitate the acquisition of data while increasing its repeatability and reliability. For example, research in spatial cognition can benefit from automated control by systematic manipulation of sensory cues and more efficient execution of training procedures. However, commercial solutions are often costly, restricted to specific platforms, and mainly focused on the automation of data acquisition, stimulus presentation, and reward delivery. Animal welfare considerations as well as experimental demands may require automating the access of an animal or animals to the experimental arena. Here, we provide and test a low-cost, versatile Raspberry Pi-based solution for such use cases. We provide four application scenarios of varying complexities, based on our research of spatial orientation and navigation in weakly electric fish, with step-by-step protocols for the control of gates in the experimental setups. This easy-to-implement, platform-independent approach can be adapted to various experimental needs, including closed-loop as well as field experiments. As such, it can contribute to the optimization and standardization of experiments in a variety of species, thereby enhancing the comparability of data.

Food intake enhances hippocampal sharp wave-ripples.

Effective regulation of energy metabolism is critical for survival. Metabolic control involves various nuclei within the hypothalamus, which receive information about the body's energy state and coordinate appropriate responses to maintain homeostasis, such as thermogenesis, pancreatic insulin secretion, and food-seeking behaviors. It has recently been found that the hippocampus, a brain region traditionally associated with memory and spatial navigation, is also involved in metabolic regulation. Specifically, hippocampal sharp wave ripples (SWRs), which are high-frequency neural oscillations supporting memory consolidation and foraging decisions, have been shown to influence peripheral glucose metabolism. However, whether SWRs are enhanced by recent feeding-when the need for glucose metabolism increases, and if so, whether feeding-dependent modulation of SWRs is communicated to other brain regions involved in metabolic regulation, remains unknown. To address these gaps, we recorded SWRs from the dorsal CA1 region of the hippocampus of mice during sleep sessions before and after consumption of meals of varying caloric values. We found that SWRs occurring during sleep are significantly enhanced following food intake, with the magnitude of enhancement being dependent on the caloric content of the meal. This pattern occurred under both food-deprived and ad libitum feeding conditions. Moreover, we demonstrate that neuronal populations in the lateral hypothalamus, which regulates food intake, exhibit robust SWR-triggered increase in activity. These findings identify the satiety state as a factor modulating SWRs and suggest that hippocampal-lateral hypothalamic communication is a potential mechanism by which SWRs could modulate peripheral metabolism and food intake.

Regulation of the NF-κB/NLRP3 signalling pathway by Shenghui Yizhi decoction reduces neuroinflammation in mice with Alzheimer’s disease

Background Shenghui Yizhi Decoction (SHYZD) has exhibited the capacity to enhance cognitive function and learning abilities in individuals diagnosed with Alzheimer’s disease (AD) while ameliorating pre-existing neuroinflammation. Nevertheless, the precise mechanism underlying its therapeutic effects on AD remains to be elucidated. Methods Twenty-four male SAMP8 mice were randomly divided into three groups, and eight male SAMR1 mice were used as a blank control, to examine their learning and spatial memory abilities. The expression of amyloid β1-42 (Aβ1-42) was detected by immunohistochemical staining of hippocampal tissue. ELISA was used to detect the interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) expressions. Real time PCR was used to detect NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cysteine protease-1 (Caspase-1), and IL-1β mRNA expression. Western blot was used to detect nuclear factor kappa-B (NF-κB), inhibitor of NF-κB α (IκBα), IκB kinase α (IKKα), NLRP3, Caspase-1, and IL-1β protein expression. Results In this study, SAMP8 mice, employed as an AD model, displayed markedly diminished abilities in terms of spatial localization, navigation, and spatial exploration when compared to the blank control group. Additionally, there was a substantial upregulation of Aβ1-42 expression in the hippocampus of these mice, along with a significant increase in the levels of inflammation-associated factors, including IL-1β, IL-6, TNF-α, NLRP3, Caspase-1, as well as the NF-κB pathway-related proteins, namely, NF-κB, IκBα, and IKKα. Moreover, after treatment with positive drugs (donepezil hydrochloride) and SHYZD, the learning abilities of the mice exhibited significant improvements. Furthermore, the hallmark AD protein Aβ1-42, inflammatory factors, and NF-κB/NLRP3 signalling pathway proteins were significantly reduced. These findings collectively suggest that SHYZD exerts a therapeutic effect on AD. Conclusion In summary, the specific molecular mechanisms through which SHYZD alleviates AD and the potential role for SHYZD in the NF-κB/NLRP3 signalling pathway are identified in this study.

Integration of auditory and visual cues in spatial navigation under normal and impaired viewing conditions.

Auditory landmarks can contribute to spatial updating during navigation with vision. Whereas large inter-individual differences have been identified in how navigators combine auditory and visual landmarks, it is still unclear under what circumstances audition is used. Further, whether or not individuals optimally combine auditory cues with visual cues to decrease the amount of perceptual uncertainty, or variability, has not been well-documented. Here, we test audiovisual integration during spatial updating in a virtual navigation task. In Experiment 1, 24 individuals with normal sensory acuity completed a triangular homing task with either visual landmarks, auditory landmarks, or both. In addition, participants experienced a fourth condition with a covert spatial conflict where auditory landmarks were rotated relative to visual landmarks. Participants generally relied more on visual landmarks than auditory landmarks and were no more accurate with multisensory cues than with vision alone. In Experiment 2, a new group of 24 individuals completed the same task, but with simulated low vision in the form of a blur filter to increase visual uncertainty. Again, participants relied more on visual landmarks than auditory ones and no multisensory benefit occurred. Participants navigating with blur did not rely more on their hearing compared with the group that navigated with normal vision. These results support previous research showing that one sensory modality at a time may be sufficient for spatial updating, even under impaired viewing conditions. Future research could investigate task- and participant-specific factors that lead to different strategies of multisensory cue combination with auditory and visual cues.

Distinct effects of slow and fast theta tACS in enhancing temporal memory

Abstract Temporal memory plays a crucial role in organizing real-life events into meaningful segments. Previous research suggests that the clustering of temporally related information builds on the neural correlates of associative memory, including theta oscillations. Transcranial alternating current stimulation (tACS) provides a means of modulating theta oscillations within associative memory networks, possibly including hippocampal modulation when targeting parietal cortex. Theta oscillations are not limited to a single frequency range, but instead, exhibit functional specialization, with slow theta (3 Hz) implicated in short-term episodic memory formation and fast theta (8 Hz) involved in spatial navigation. This study aimed to investigate the distinct effects of slow and fast theta stimulation on temporal memory. Participants encoded visual objects paired with frame color while receiving tACS stimulation at 8 Hz, 3 Hz, or sham targeting the left parietal cortex. The frame color would change for every eight objects, establishing a context boundary with each color change. Subsequently, participants performed a timeline task to assess temporal memory performance. Results showed that slow, but not fast, theta stimulation led to an enhancement in temporal accuracy (absolute temporal error) compared to sham tACS, in support of our main hypothesis. Under sham stimulation, participants consistently underestimated the temporal position of items presented further away from boundary, compared to those presented at boundary. This finding resembled temporal compression observed during event segmentation. Interestingly, fast, but not slow, theta stimulation reduced this temporal bias (rated position— actual position). This study represents the first tACS evidence for differential contributions of slow versus fast theta to temporal memory formation in humans. We speculate that parietal theta tACS may modulate the hippocampus and facilitate temporal memory formation.

Neuronal Vulnerability of the Entorhinal Cortex to Tau Pathology in Alzheimer's Disease.

This review delves into the entorhinal cortex (EC) as a central player in the pathogenesis of Alzheimer's Disease (AD), emphasizing its role in the accumulation and propagation of tau pathology. It elucidates the multifaceted functions of the EC, encompassing memory formation, spatial navigation, and olfactory processing, while exploring how disruptions in these processes contribute to cognitive decline in AD. The review discusses the intricate interplay between tau pathology and EC vulnerability, highlighting how alterations in neuronal firing patterns and synaptic function within the EC exacerbate cognitive impairments. Furthermore, it elucidates how specific neuronal subtypes within the EC exhibit differential susceptibility to tau-induced damage, contributing to disease progression. Early detection methods, such as imaging techniques and assessments of EC blood flow, are examined as potential tools for identifying tau pathology in the preclinical stages of AD. These approaches offer promise for improving diagnostic accuracy and enabling timely intervention. Therapeutic strategies targeting tau pathology within the EC are explored, including the clearance of pathological tau aggregates and the inhibition of tau aggregation processes. By understanding the molecular and cellular mechanisms underlying EC vulnerability, researchers can develop more targeted and effective interventions to slow disease progression. The review underscores the importance of reliable biomarkers to assess disease progression and therapeutic efficacy in clinical trials targeting the EC. Ultimately, it aims to contribute to the development of more effective management strategies for AD, emphasizing the translation of research findings into clinical practice to address the growing societal burden of the disease.

Identifying older adults at risk for dementia based on smartphone data obtained during a wayfinding task in the real world.

Alzheimer's disease (AD), as the most common form of dementia and leading cause for disability and death in old age, represents a major burden to healthcare systems worldwide. For the development of disease-modifying interventions and treatments, the detection of cognitive changes at the earliest disease stages is crucial. Recent advancements in mobile consumer technologies provide new opportunities to collect multi-dimensional data in real-life settings to identify and monitor at-risk individuals. Based on evidence showing that deficits in spatial navigation are a common hallmark of dementia, we assessed whether a memory clinic sample of patients with subjective cognitive decline (SCD) who still scored normally on neuropsychological assessments show differences in smartphone-assisted wayfinding behavior compared with cognitively healthy older and younger adults. Guided by a mobile application, participants had to find locations along a short route on the medical campus of the Magdeburg university. We show that performance measures that were extracted from GPS and user input data distinguish between the groups. In particular, the number of orientation stops was predictive of the SCD status in older participants. Our data suggest that subtle cognitive changes in patients with SCD, whose risk to develop dementia in the future is elevated, can be inferred from smartphone data, collected during a brief wayfinding task in the real world.

Transcriptomic Signature of Spatial Navigation in Brains ofDesert Ants.

Navigation is crucial for central-place foragers to locate food and return to the nest. Cataglyphis ants are renowned for their advanced navigation abilities, relying on landmark cues and path integration. This study aims to uncover the transcriptomic basis of exceptional spatial learning in the central nervous system of Cataglyphis niger. Ants navigated a maze with a food reward, and we examined expression changes linked to correct decisions in subsequent runs. Correct decisions correlated with expression changes in the optic lobes, but not the central brain, showing a downregulation of genes associated with sucrose response and Creb3l1. The latter gene is homologous to Drosophila crebA, which is essential for long-term memory formation. To understand how ants use distance information during path integration, we analyzed expression shifts associated with the last distance traveled. We uncovered a transcriptomic footprint in the central brain, but not in the optic lobes, with genes enriched for energy consumption and neurological functions, including neuronal projection development, synaptic target inhibition, and recognition processes. This suggests that transcriptional activity in the central brain is necessary for estimating distance traveled, which is crucial for path integration. Our study supports the distinct roles of different brain parts for navigation in Cataglyphis ants.

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.

Investigating Transcutaneous Vagus Nerve Stimulation in Amnestic Mild Cognitive Impairment

Abstract Background New treatments are urgently needed for individuals with Mild Cognitive Impairment (MCI) - in particular for those with amnestic MCI, of whom a high proportion have underlying Alzheimer's Disease (AD). Transcutaneous Vagus Nerve Stimulation (tVNS) is a non-invasive neuro-modulatory treatment which has not been extensively examined in older adults with amnestic MCI. Methods A single site, single-blind, randomised three-arm crossover pilot trial of acute (60 minutes) tVNS (baseline, sham or active stimulation) was conducted a Regional Specialist Memory Service. Forty participants (age 71.7 ±6.9; 22/40 male) with diagnosed amnestic MCI were recruited. Given the links between AD and neuro-cardiovascular instability, potential adverse effects of active tVNS were assessed using beat-to-beat peripheral (Blood Pressure (BP) and Heart Rate [HR]) and central (via Near Infra-red Spectroscopy) haemodynamic responses to Active Stand (AS). Cognition was assessed between 21.3 ±4.9 and 60.5 ±4.4 minutes using a domain-specific cognitive performance battery with results analysed using mixed-effects linear regression. Results In older adults with amnestic MCI, tVNS was safe, tolerable and acceptable with 98% of participants stating they would use the device again. There was no significant effect on BP, or HR responses to AS and cerebral oxygenation remained stable during AS. After tVNS stimulation, performance on tests of spatial navigation were significantly improved compared to both baseline (ß= -8.76; [-14.91, -2.56]; p=0.01) and sham (ß= -4.15; [-7.32, -0.99]; p=0.01) conditions. Conclusion tVNS is a safe and tolerable treatment modality in older adults with amnestic MCI. Future studies should explore sustained effects and feasibility of domiciliary use.

Spatial maps in piriform cortex during olfactory navigation.

Odors are a fundamental part of the sensory environment used by animals to inform behaviors such as foraging and navigation1,2. Primary olfactory (piriform) cortex is thought to be dedicated to encoding odor identity3-8. Here, using neural ensemble recordings in freely moving rats performing a novel odor-cued spatial choice task, we show that posterior piriform cortex neurons also carry a robust spatial map of the environment. Piriform spatial maps were stable across behavioral contexts independent of olfactory drive or reward availability, and the accuracy of spatial information carried by individual neurons depended on the strength of their functional coupling to the hippocampal theta rhythm. Ensembles of piriform neurons concurrently represented odor identity as well as spatial locations of animals, forming an "olfactory-place map". Our results reveal a previously unknown function for piriform cortex in spatial cognition and suggest that it is well-suited to form odor-place associations and guide olfactory cued spatial navigation.

Assessing rapid spatial working memory in community-living older adults in a virtual adaptation of the rodent water maze paradigm

Aging often leads to a decline in various cognitive domains, potentially contributing to spatial navigation challenges among older individuals. While the Morris water maze is a common tool in rodents research for evaluating allocentric spatial memory function, its translation to studying aging in humans, particularly its association with hippocampal dysfunction, has predominantly focused on spatial reference memory assessments. This study expanded the adaptation of the Morris water maze for older adults to assess flexible, rapid, one-trial working memory. This adaptation involved a spatial search task guided by allocentric cues within a 3-D virtual reality (VR) environment. The sensitivity of this approach to aging was examined in 146 community-living adults from three Chinese cities, categorized into three age groups. Significant performance deficits were observed in participants over 60 years old compared to younger adults aged between 18 and 43. However, interpreting these findings was complicated by factors such as psychomotor slowness and potential variations in task engagement, except during the probe tests. Notably, the transition from the 60 s to the 70 s was not associated with a substantial deterioration of performance. A distinction only emerged when the pattern of spatial search over the entire maze was examined in the probe tests when the target location was never revealed. The VR task's sensitivity to overall cognitive function in older adults was reinforced by the correlation between Montreal Cognitive Assessment (MoCA) scores and probe test performance, demonstrating up to 17 % shared variance beyond that predicted by chronological age alone. In conclusion, while implementing a VR-based adaptation of rodent water maze paradigms in older adults was feasible, our experience highlighted specific interpretative challenges that must be addressed before such a test can effectively supplement traditional cognitive assessment tools in evaluating age-related cognitive decline.

Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.

Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refers to one's level of confidence in their ability to balance while completing activities of daily living like getting dressed, bathing, and walking. Lower self-efficacy, or greater FoF during these activities is a function of motor, cognitive, and emotional impairments and may impact quality of life in PD. Unlike known cholinergic reduction, especially in the right lateral geniculate and caudate nuclei, little is known about the role of cholinergic transporters in FoF or mobility self-efficacy in PD. [18F]fluoroethoxybenzovesamicol ([18F]FEOBV) positron emission tomography (PET) studies were conducted to assess vesicular acetylcholine transporter (VAChT) expression in 126 patients with PD (male (m) = 95, female (f) = 31). Participants had a mean age of 67.3 years (standard deviation (SD) = 7.1) and median Hoehn Yahr stage of 2.5. Patients also completed the Short Falls Efficacy Scale (sFES-I) as a survey measure of concerns about falling. [18F]FEOBV data were processed in Statistical Parametric Mapping (SPM) using a voxel-wise regression model with sFES-I scores as the outcome measure. Reduced [18F]FEOBV binding in tectum, metathalamic (lateral more than medial geniculate nuclei), thalamus proper, bilateral mesiotemporal (hippocampal, parahippocampal, fusiform gyri and fimbriae), and right cerebellar lobule VI significantly associated with higher sFES-I scores (p < 0.05, family-wise error (FWE) correction after Threshold-Free Cluster Enhancement (TFCE)). Unlike the more limited involvement of the brainstem-thalamic complex and caudate nuclei cholinergic topography associated with falls in PD, cholinergic reductions in the extended connectivity between the thalamic complex and the temporal limbic system via the fimbriae associates with FoF. Additional cholinergic changes were seen in the cerebellum. The temporal limbic system plays a role not only in episodic memory but also in spatial navigation, scene and contextual (e.g., emotional) processing. Findings may augur novel therapeutic approaches to treat poor mobility self-efficacy in PD. No: NCT02458430. Registered 18 March, 2015, https://www. gov/study/NCT02458430; No: NCT05459753. Registered 01 July, 2022, https://www. gov/study/NCT05459753.

The hippocampus pre-orders movements for skilled action sequences.

Plasticity in the subcortical motor basal ganglia-thalamo-cerebellar network plays a key role in the acquisition and control of long-term memory for new procedural skills, from the formation of population trajectories controlling trained motor skills in the striatum to the adaptation of sensorimotor maps in the cerebellum. However, recent findings demonstrate the involvement of a wider cortical and subcortical brain network in the consolidation and control of well-trained actions, including of a brain region traditionally associated with declarative memory - the hippocampus. Here, we probe which role these subcortical areas play in skilled motor sequence control, from sequence feature selection during planning to their integration during sequence execution. An fMRI dataset (N=24, 14 female) collected after participants learnt to produce four finger press sequences entirely from memory with high movement and timing accuracy over several days was examined for both changes in BOLD activity and their informational content in subcortical regions of interest. Although there was a widespread activity increase in effector-related striatal, thalamic and cerebellar regions, in particular during sequence execution, the associated activity did not contain information on the motor sequence identity. In contrast, hippocampal activity increased during planning and predicted the order of the upcoming sequence of movements. Our findings suggests that the hippocampus pre-orders movements for skilled action sequences, thus contributing to the higher-order control of skilled movements that require flexible retrieval. These findings challenge the traditional taxonomy of episodic and procedural memory and carry implications for the rehabilitation of individuals with neurodegenerative disorders.Significance statement Skilled actions like handwriting, typing, and playing music, involve recombining movements into various sequences and producing them from memory. This fMRI study suggests that the hippocampus, traditionally associated with episodic memory and spatial navigation, pre-orders well-trained movement sequences prior to their execution. These findings challenge the canonical separation between episodic and procedural memory systems and the neural basis of skilled motor behaviours.

Unique Transcriptomic Cell Types of the Granular Retrosplenial Cortex are Preserved Across Mice and Rats Despite Dramatic Changes in Key Marker Genes.

The granular retrosplenial cortex (RSG) supports key functions ranging from memory consolidation to spatial navigation. The mouse RSG contains several cell types that are remarkably distinct from those found in other cortical regions. This includes the physiologically and transcriptomically unique low rheobase neuron that is the dominant cell-type in RSG layers 2/3 (L2/3 LR), as well as the similarly exclusive pyramidal cells that comprise much of RSG layer 5a (L5a RSG). While the functions of the RSG are extensively studied in both mice and rats, it remains unknown if the transcriptomically unique cell types of the mouse RSG are evolutionarily conserved in rats. Here, we show that mouse and rat RSG not only contain the same cell types, but key subtypes including the L2/3 LR and L5a RSG neurons are amplified in their representations in rats compared to mice. This preservation of cell types in male and female rats happens despite dramatic changes in key cell-type-specific marker genes, with the Scnn1a expression that selectively tags mouse L5a RSG neurons completely absent in rats. Important for Cre-driver line development, we identify alternative, cross-species genes that can be used to selectively target the cell types of the RSG in both mice and rats. Our results show that the unique cell types of the RSG are evolutionarily conserved across millions of years of evolution between mice and rats, but also emphasize stark species-specific differences in marker genes that need to be considered when making cell-type-specific transgenic lines of mice versus rats.

Behavioral Alterations of Spatial Cognition and Role of the Apolipoprotein E-ε4 in Patients with MCI Due to Alzheimer's Disease: Results from the BDSC-MCI Project.

Background: Beyond memory deterioration, spatial disorientation may occur along the continuum of normal aging-dementia of Alzheimer's type. The present study aims at detecting behavioral disorders of spatial cognition in prodromal Alzheimer's disease (AD) and verifying the association between Apolipoprotein E-ε4 (ApoE-ε4) genotype and gait patterns during a real-world naturalistic task. Methods: A sample of 58 elderly participants, of which 20 patients with mild cognitive impairment with CFS biomarker evidence of AD, 23 individuals with subjective cognitive decline (SCD), and 15 healthy controls (HCs), was tested by a modified version of the Detour Navigation Test (DNT-mv). Generalized linear models were run to explore the association between group belonging and wrong turns (WTs)/moments of hesitation (MsH) as behavioral disorientation scores of the DNT-mv as well as the effect of ApoE-ε4 genotype on time and walking speed registered by a smartphone app providing GPS tracking of body movement around urban environments. Results: Patients with MCI due to AD reported more WTs than individuals with SCD and HCs. Further, the ApoE-ε4 genotype determined a lower capacity in spatial information processing, influencing gait during naturalistic spatial navigation tasks. Conclusions: Behavior alterations of spatial cognition can be detected ecologically in prodromal AD. The use of technological solutions supporting gait analysis may help in corroborating the experimental observation.

FOS mapping reveals two complementary circuits for spatial navigation in mouse

Here, we show that during continuous navigation in a dynamic external environment, mice are capable of developing a foraging strategy based exclusively on changing distal (allothetic) information and that this process may involve two alternative components of the spatial memory circuit: the hippocampus and retrosplenial cortex. To this end, we designed a novel custom apparatus and implemented a behavioral protocol based on the figure-8-maze paradigm with two goal locations associated with distinct contexts. We assessed whether mice are able to learn to retrieve a sequence of rewards guided exclusively by the changing context. We found out that training mice in the apparatus leads to change in strategy from the internal tendency to alternate into navigation based exclusively on visual information. This effect could be achieved using two different training protocols: prolonged alternation training, or a flexible protocol with unpredictable turn succession. Based on the c-FOS mapping we also provide evidence of opposing levels of engagement of hippocampus and retrosplenial cortex after training of mice in these two different regimens. This supports the hypothesis of the existence of parallel circuits guiding spatial navigation, one based on the well-described hippocampal representation, and another, RSC-dependent.