Effects of estrogen on spatial navigation and memory.

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.

Contribution of the medial entorhinal cortex to performance on the Traveling Salesperson Problem in rats.

In order to successfully navigate through space, animals must rely on multiple cognitive processes, including orientation in space, memory of object locations, and navigational decisions based on that information. Although highly-controlled behavioral tasks are valuable for isolating and targeting specific processes, they risk producing a narrow understanding of complex behavior in natural contexts. The Traveling Salesperson Problem (TSP) is an optimization problem that can be used to study naturalistic foraging behaviors, in which subjects select routes between multiple baited targets. Foraging is a spontaneous, yet complex, behavior, involving decision-making, attention, course planning, and memory. Previous research found that hippocampal lesions in rats impaired TSP task performance, particularly on measures of spatial memory. Although traditional laboratory tests have shown the medial entorhinal cortex (MEC) to play an important role in spatial memory, if and how the MEC is involved in finding efficient solutions to the TSP remains unknown. In the current study, rats were trained on the TSP, learning to retrieve bait from targets in a variety of spatial configurations. After recovering from either an MEC lesion or control sham surgery, the rats were tested on eight new configurations. Our results showed that, similar to rats with hippocampal lesions, MEC-lesioned rats were impaired on measures of spatial memory, but not spatial decision-making, with greatest impairments on configurations requiring a global navigational strategy for selecting the optimal route. These findings suggest that the MEC is important for effective spatial navigation, especially when global cue processing is required.

A cell-type-specific error-correction signal in the posterior parietal cortex.

Neurons in the posterior parietal cortex contribute to the execution of goal-directed navigation1 and other decision-making tasks2-4. Although molecular studies have catalogued more than 50 cortical cell types5, it remains unclear what distinct functions they have in this area. Here we identified a molecularly defined subset of somatostatin (Sst) inhibitory neurons that, in the mouse posterior parietal cortex, carry a cell-type-specific error-correction signal for navigation. We obtained repeatable experimental access to these cells using an adeno-associated virus in which gene expression is driven by an enhancer that functions specifically in a subset of Sst cells6. We found that during goal-directed navigation in a virtual environment, this subset of Sst neurons activates in a synchronous pattern that is distinct from the activity of surrounding neurons, including other Sst neurons. Using in vivo two-photon photostimulation and ex vivo paired patch-clamp recordings, we show that nearby cells of this Sst subtype excite each other through gap junctions, revealing a self-excitation circuit motif that contributes to the synchronous activity of this cell type. These cells selectively activate as mice execute course corrections for deviations in their virtual heading during navigation towards a reward location, for both self-induced and experimentally induced deviations. We propose that this subtype of Sst neurons provides a self-reinforcing and cell-type-specific error-correction signal in the posterior parietal cortex that may help with the execution and learning of accurate goal-directed navigation trajectories.

AllenDigger, a Tool for Spatial Expression Data Visualization, Spatial Heterogeneity Delineation, and Single-Cell Registration Based on the Allen Brain Atlas.

Spatial transcriptomics can be used to capture cellular spatial organization and has facilitated new insights into different biological contexts, including developmental biology, cancer, and neuroscience. However, its wide application is still hindered by its technical challenges and immature data analysis methods. Allen Brain Atlas (ABA) provides a great source for spatial gene expression throughout the mouse brain at various developmental stages with in situ hybridization image data. To the best of our knowledge, the portal developed to access spatial expression data is not very useful to biologists. Here, we developed a toolkit to collect and preprocess expression data from the ABA and allow a friendlier query to visualize the spatial distribution of genes of interest, characterize the spatial heterogeneity of the brain, and register cells from single-cell transcriptomics data to fine anatomical brain regions via machine learning methods with high accuracy. AllenDigger will be very helpful to the community in precise spatial gene expression queries and add extra spatial information to further interpret the scRNA-seq data in a cost-effective manner.

The role of progesterone in memory bias during spatial navigation in females.

Rats can use several memory systems to navigate a maze toward a reward. Two of these are place memory and response memory and female rats can be biased to predominantly use one over another. Both progesterone and estrogens have been shown to alter memory bias. Although the effects of estrogens have been well documented, the effects of progesterone remain somewhat unexplored. Mechanisms through which progesterone may be acting to exert its effects are reviewed here. Converging evidence suggests that the actions of progesterone differ depending on the presence of estrogens, frequently acting in opposition to estrogens when administered together. The hippocampus, dorsal striatum, and prefrontal cortex are likely involved, as is the progesterone metabolite, allopregnanolone. There is a need for more research on progesterone and memory bias, especially considering current formulations of hormonal contraceptives include progestins.

A robotic model of hippocampal reverse replay for reinforcement learning.

Hippocampal reverse replay, a phenomenon in which recently active hippocampal cells reactivate in the reverse order, is thought to contribute to learning, particularly reinforcement learning (RL), in animals. Here, we present a novel computational model which exploits reverse replay to improve stability and performance on a homing task. The model takes inspiration from the hippocampal-striatal network, and learning occurs via a three-factor RL rule. To augment this model with hippocampal reverse replay, we derived a policy gradient learning rule that associates place-cell activity with responses in cells representing actions and a supervised learning rule of the same form, interpreting the replay activity as a 'target' frequency. We evaluated the model using a simulated robot spatial navigation task inspired by the Morris water maze. Results suggest that reverse replay can improve performance stability over multiple trials. Our model exploits reverse reply as an additional source for propagating information about desirable synaptic changes, reducing the requirements for long-time scales in eligibility traces combined with low learning rates. We conclude that reverse replay can positively contribute to RL, although less stable learning is possible in its absence. Analogously, we postulate that reverse replay may enhance RL in the mammalian hippocampal-striatal system rather than provide its core mechanism.

The development of visuospatial abilities and their impact on laparoscopic skill acquisition: a clinical longitudinal study.

OBJECTIVES: To investigate how visuospatial abilities develop and influence intraoperative laparoscopic performance during surgical residency training programmes. BACKGROUND: Laparoscopic surgery is a challenging technique to acquire and master. Visuospatial ability is an important attribute but most prior research have predominantly explored the influence of visuospatial abilities in lab-based settings and/or among inexperienced surgeons. Little is known about the impact of visuospatial profiles on actual laparoscopic performance and its role in shaping competency. METHOD: A longitudinal observational cohort study using a pair-matched design over 27 months. At baseline, visuospatial profiles of 43 laparoscopic surgeons of all expertise levels and 19 control subjects were compared. The development of visuospatial abilities and their association with intraoperative performance of 18 residency surgeons were monitored during the course of their laparoscopic training. RESULTS: Laparoscopic surgeons significantly outperformed the control group on the measure of spatial visualisation (U = 273.0, p = 0.03, η2 = 0.3). Spatial visualisation was found to be a significant predictor of laparoscopic expertise (R2 = 0.70, F (1.60) = 6.788, p = 0.01) and improved with laparoscopic training (B = 4.01, SE = 1.83, p = 0.02, 95% CI [0.40, 7.63]). From month 6 to 18, a strong positive correlation between spatial visualisation and intraoperative depth perception (r = 0.67, p < 0.01), bimanual dexterity (r = 0.60, p < 0.01), autonomy (r = 0.78, p < 0.01) and the total score (r = 0.70, p < 0.01) were observed but a strong relationship remained only with autonomy (r = 0.89, p < 0.01) and total score (r = 0.80, p < 0.01) at 18 months. CONCLUSION: In this longitudinal cohort study, visuospatial abilities associate with laparoscopic skills and improve with training. Spatial visualisation may be characteristic of laparoscopic expertise as it has clear association with competency development during laparoscopy residency training programme.

Progesterone rapidly alters the use of place and response memory during spatial navigation in female rats.

17ß-Estradiol (E2) and progesterone (P) influence place and response memory in female rats in spatial navigation tasks. Use of these memory systems is associated with the hippocampus and the dorsal striatum, respectively. Injections of E2 result in a well-established bias to use place memory, while much less is understood about the role of P. A total of 120 ovariectomized female rats were tested within a dual-solution T-maze task and treated with either low E2 (n = 24), high E2 (10 µg/kg; n = 24), or high E2 in combination with P (500 µg/kg) at three time points before testing: 15 min (n = 24), 1 h (n = 24), and 4 h (n = 24). Given alone, high E2 biases rats to the use of place memory, but this effect is reversed when P is given 1 h or 4 h before testing. This indicates that P may be playing an inhibitory role in the hippocampus during spatial tasks, which is consistent with past findings. Our findings show that P acts rapidly (within an hour) to affect performance during spatial tasks.

The influence of estradiol and progesterone on neurocognition during three phases of the menstrual cycle: Modulating factors.

Estradiol is an ovarian steroid hormone that peaks shortly before ovulation and significantly affects various brain regions and neurotransmitter systems, with similar and differential effects with progesterone, another ovarian hormone. Studies investigating the neurocognitive processes during the menstrual cycle have focused on the early follicular phase (EFP) characterized by low estradiol and progesterone levels and the mid-luteal phase (MLP) with high estradiol and progesterone levels. However, most studies have failed to include the ovulatory phase, characterized by high estradiol and low progesterone levels. Given the various hormonal changes in the menstrual cycle, we revisited studies suggesting that the menstrual cycle did not affect verbal and spatial abilities and observed that many contain mixed results. Comparing these studies makes it possible to identify relevant modulating factors, such as sample size, participant age, accurate selection of days for testing, asymmetrical practice effects, genetic polymorphisms, and task difficulty. More robust findings are related to improved mental rotation capacity during EFP with challenging tasks and differences in brain activation among menstrual cycle phases during the execution of spatial and verbal tasks. During MLP, less robust findings were observed, possibly modulated by the complex effects of the two hormones on the brain. In conclusion, we propose that it is crucial to include all three menstrual cycle phases and consider these modulating factors to avoid confounding findings.

From fish out of water to new insights on navigation mechanisms in animals.

Navigation is a critical ability for animal survival and is important for food foraging, finding shelter, seeking mates and a variety of other behaviors. Given their fundamental role and universal function in the animal kingdom, it makes sense to explore whether space representation and navigation mechanisms are dependent on the species, ecological system, brain structures, or whether they share general and universal properties. One way to explore this issue behaviorally is by domain transfer methodology, where one species is embedded in another species' environment and must cope with an otherwise familiar (in our case, navigation) task. Here we push this idea to the limit by studying the navigation ability of a fish in a terrestrial environment. For this purpose, we trained goldfish to use a Fish Operated Vehicle (FOV), a wheeled terrestrial platform that reacts to the fish's movement characteristics, location and orientation in its water tank to change the vehicle's; i.e., the water tank's, position in the arena. The fish were tasked to "drive" the FOV towards a visual target in the terrestrial environment, which was observable through the walls of the tank, and indeed were able to operate the vehicle, explore the new environment, and reach the target regardless of the starting point, all while avoiding dead-ends and correcting location inaccuracies. These results demonstrate how a fish was able to transfer its space representation and navigation skills to a wholly different terrestrial environment, thus supporting the hypothesis that the former possess a universal quality that is species-independent.

The role of virtual reality simulation in surgical training in the light of COVID-19 pandemic: Visual spatial ability as a predictor for improved surgical performance: a randomized trial.

INTRODUCTION: Due to the current COVID-19 pandemic, surgical training has become increasingly challenging due to required social distancing. Therefore, the use of virtual reality (VR)-simulation could be a helpful tool for imparting surgical skills, especially in minimally invasive environments. Visual spatial ability (VSA) might influence the learning curve for laparoscopic surgical skills. However, little is known about the influence of VSA for surgical novices on VR-simulator training regarding the complexity of different tasks over a long-term training period. Our study evaluated prior VSA and VSA development in surgical trainees during VR-simulator training, and its influence on surgical performance in simulator training. METHODS: In our single-center prospective two-arm randomized trial, VSA was measured with a tube figure test before curriculum training. After 1:1 randomization, the training group (TG) participated in the entire curriculum training consisting of 48 different VR-simulator tasks with varying difficulty over a continuous nine-day training session. The control group (CG) performed two of these tasks on day 1 and 9. Correlation and regression analyses were used to assess the influence of VSA on VR-related surgical skills and to measure procedural abilities. RESULTS: Sixty students (33 women) were included. Significant improvements in the TG in surgical performance and faster completion times were observed from days 1 to 9 for the scope orientation 30° right-handed (SOR), and cholecystectomy dissection tasks after the structured 9-day training program. After training, the TG with pre-existing low VSA scores achieved performance levels similar to those with pre-existing high VSA scores for the two VR simulator tasks. Significant correlations between VSA and surgical performance on complex laparoscopic camera navigation SOR tasks were found before training. CONCLUSIONS: Our study revealed that that all trainees improved their surgical skills irrespective of previous VSA during structured VR simulator training. An increase in VSA resulted in improvements in surgical performance and training progress, which was more distinct in complex simulator tasks. Further, we demonstrated a positive relationship between VSA and surgical performance of the TG, especially at the beginning of training. Our results identified pre-existing levels of VSA as a predictor of surgical performance.

Effects of Antibodies to Glutamate on Cerebral Expression of the Tnfrsf1A Gene under Conditions of Spatial Amnesia Induced by Proinflammatory Protein S100A9 Fibrils in Aging Mice.

Proinflammatory S100A9 protein is a promoter of inflammation-linked neurodegeneration and the Tnfrsf1A gene encodes the TNF receptor 1A that binds TNFα to function as a regulator of inflammation. We studied the effects of chronic intranasal administration of in vitro prepared S100A9 fibrils alone or in combination with anti-glutamate antibodies on the expression of the Tnfrsf1A gene in the hippocampus, prefrontal cortex, and cerebellum of aging C57BL/6 mice under conditions of impaired spatial memory. A differential cerebral pattern of Tnfrsf1A gene activity and its modification by S100A9 fibrillar structures were observed: inhibition of Tnfrsf1A gene expression in the hippocampus and cerebellum and its activation in the prefrontal cortex. Anti-glutamate antibodies normalized the expression of the Tnfrsf1A gene in the prefrontal cortex by affecting the TNF signaling pathway and preventing the development of inflammation.

Beyond the Mini-Mental State Examination: The Use of Physical and Spatial Navigation Tests to Help to Screen for Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Spatial navigation and dual-task (DT) performance may represent a low-cost approach to the identification of the cognitive decline in older adults and may support the clinical diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). OBJECTIVE: To assess the accuracy of different types of motor tasks in differentiating older persons with MCI and AD from healthy peers. METHODS: Older adults aged 60 years or over (n = 105; healthy = 39; MCI = 23; AD = 43) were evaluated by the floor maze test (FMT), the senior fitness test, and DT performance. Receiver operating characteristic curve (ROC) analysis was used to evaluate the accuracy of the tests. We also performed principal component analysis (PCA) and logistic regression analysis to explore the variance and possible associations of the variables within the sample. RESULTS: FMT (AUC = 0.84, sensitivity = 75.7%, specificity = 76.1%, p < 0.001) and DT (AUC = 0.87, sensitivity = 80.4%, specificity = 86.9%, p < 0.001) showed the highest performance for distinguishing MCI from AD individuals. Moreover, FMT presented better sensitivity in distinguishing AD patients from their healthy peers (AUC = 0.93, sensitivity = 94%, specificity = 85.6%, p < 0.001) when compared to the Mini-Mental State Examination. PCA revealed that the motor test performance explains a total of 73.9% of the variance of the sample. Additionally, the results of the motor tests were not influenced by age and education. CONCLUSION: Spatial navigation tests showed better accuracy than usual cognitive screening tests in distinguishing patients with neurocognitive disorders.

Cultural Change Reduces Gender Differences in Mobility and Spatial Ability among Seminomadic Pastoralist-Forager Children in Northern Namibia.

A fundamental cognitive function found across a wide range of species and necessary for survival is the ability to navigate complex environments. It has been suggested that mobility may play an important role in the development of spatial skills. Despite evolutionary arguments offering logical explanations for why sex/gender differences in spatial abilities and mobility might exist, thus far there has been limited sampling from nonindustrialized and subsistence-based societies. This lack of sampling diversity has left many unanswered questions regarding the effects that environmental variation and cultural norms may have in shaping mobility patterns during childhood and the development of spatial competencies that may be associated with it. Here we examine variation in mobility (through GPS tracking and interviews), performance on large-scale spatial skills (i.e., navigational ability), and performance on small-scale spatial skills (e.g., mental rotation task, Corsi blocks task, and water-level task) among Twa forager/pastoralist children whose daily lives have been dramatically altered since settlement and the introduction of government-funded boarding schools. Unlike in previous findings among Twa adults, boys and girls (N = 88; aged 6-18) show similar patterns of travel on all measures of mobility. We also find no significant differences in spatial task performance by gender for large- or small-scale spatial skills. Further, children performed as well as adults did on mental rotation, and they outperformed adults on the water-level task. We discuss how children's early learning environments may influence the development of both large- and small-scale spatial skills.

Health risks of exposure to soil-borne dichlorodiphenyltrichloroethanes (DDTs): A preliminary probabilistic assessment and spatial visualization.

Residues of dichlorodiphenyltrichloroethane and its metabolites (DDTs) in soils continue to severely threaten and endanger human health. This present study comprehensively interprets the health risks associated with exposure to soil-borne DDTs and also identifies the spatial visualization of risks at a large regional scale in Fujian, China. There was significant spatial variability of human risk across the region, while levels of health risk displayed a significant positive correlation with population density (p < 0.05). High risk levels occurred mostly in the coastal areas in northeastern Fujian, with additional hotspots in inland areas. The highest total incremental lifetime cancer risks (ILCRs) occurred in Sanming, reaching up to 9.52 × 10-5, 3.27 × 10-5, and 1.76 × 10-4 for children, teens, and adults, respectively. Further, the highest hazard index (HI) value was observed in Fuzhou, reaching up to 6.09, 3.84, and 2.37, respectively. The 95% confidence interval of data regarding ILCRs exceeded the recognized safe threshold, whereas the HI has been deemed accepted. Adults were identified as the most susceptible population in terms of cancer risks, with o,p'-DDT being the primary contributor of ILCRs. Moreover, children were showed to be the most vulnerable in terms of non-cancer risks, with p,p'-DDD being the main contributor of HI. Food ingestion appeared to be the dominant exposure pathway, for both cancer and non-cancer risks. The concentration of DDTs (Csoil) and exposure duration (ED) also greatly influenced the risk, together contributing to over 99% of the ILCRs and HI.

Contribution of the hippocampus to performance on the traveling salesperson problem in rats.

The Traveling Salesman Problem (TSP) is an optimization problem in which the subject attempts to find the shortest possible route that passes through a set of fixed locations exactly once. The TSP is used in cognitive and behavioral research to study problem solving and spatial navigation. While the TSP has been studied in some depth from this perspective, the biological mechanisms underlying the behavior have not yet been explored. The hippocampus is a structure in the brain that is known to be involved in tasks that require spatial memory. Because the TSP requires spatial problem solving, we designed the current study to determine whether the hippocampus is required to find efficient solutions to the TSP, and if so, what role the hippocampus serves. Rats were pretrained on the TSP, which involved learning to retrieve bait from targets in a variety of spatial configurations. Matched for performance, rats were then divided into two groups, receiving either a hippocampal lesion or a control sham surgery. After recovering from surgery, the rats were tested on eight new configurations. A variety of behavioral measures were recorded, including distance travelled, number of revisits, memory span, and latency. The results showed that the sham group outperformed the lesion group on most of these measures. Based on the behavioral data and histological tissue analysis of each group, we determined that the hippocampus is involved in successful performance in the TSP, particularly regarding memory for which targets have already been visited.

N-Acetylcysteine Attenuates the Anxiety-Like Behavior and Spatial Cognition Impairment Induced by Doxorubicin and Cyclophosphamide Combination Treatment in Rats.

BACKGROUND: Cancer patients can suffer from psychological and cognitive disorders after chemotherapy, which influence quality of life. OBJECTIVE: Oxidative stress may contribute to the psychological and cognitive disorders induced in rats by chemotherapy. In the present study, we examined the effects of N-acetylcysteine, an anti-oxidant, on anxiety-like behavior and cognitive impairment in rats treated with a combination of doxorubicin and cyclophosphamide. METHODS: Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. The light-dark test and the novel location recognition test were used to assess anxiety-like behavior and spatial cognition, respectively. The rats' hippocampal levels of glutathione (GSH) and glutathione disulfide (GSSG) were measured using a GSSG/GSH quantification kit. RESULTS: Combined treatment with doxorubicin and cyclophosphamide produced anxiety-like behavior and cognitive impairment in rats. N-acetylcysteine reversed the anxiety-like behavior and inhibition of novel location recognition induced by the combination treatment. Furthermore, the combination of doxorubicin and cyclophosphamide significantly reduced the rats' hippocampal GSH/GSSG ratios. N-acetylcysteine reversed the reduction in the GSH/GSSG ratio seen in the doxorubicin and cyclophosphamide-treated rats. CONCLUSION: These results suggest that N-acetylcysteine inhibits doxorubicin and cyclophosphamide-induced anxiety-like behavior and cognitive impairment by reducing oxidative stress in the hippocampus.

Physician Wellness in Orthopedic Surgery: Challenges and Solutions.

The growing epidemic of physician burnout suggests that a change is needed. Physician wellness is an ever-growing consideration, especially in orthopedic surgery, where the challenges to wellness are significant. This review provides many common sense wellness principles and solutions in four main components of wellness (physical, mental, emotional, and spiritual) interwoven with current research on the topic. Although directed to orthopedic surgeons, this guide can be applied to all physicians, because they are based on common human principles of wellness. Wellness is not created overnight, so wellness practices that increase the likelihood of experiencing wellness are encouraged.

Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network.

Behavioural experiences activate the FOS transcription factor in sparse populations of neurons that are critical for encoding and recalling specific events1-3. However, there is limited understanding of the mechanisms by which experience drives circuit reorganization to establish a network of Fos-activated cells. It is also not known whether FOS is required in this process beyond serving as a marker of recent neural activity and, if so, which of its many gene targets underlie circuit reorganization. Here we demonstrate that when mice engage in spatial exploration of novel environments, perisomatic inhibition of Fos-activated hippocampal CA1 pyramidal neurons by parvalbumin-expressing interneurons is enhanced, whereas perisomatic inhibition by cholecystokinin-expressing interneurons is weakened. This bidirectional modulation of inhibition is abolished when the function of the FOS transcription factor complex is disrupted. Single-cell RNA-sequencing, ribosome-associated mRNA profiling and chromatin analyses, combined with electrophysiology, reveal that FOS activates the transcription of Scg2, a gene that encodes multiple distinct neuropeptides, to coordinate these changes in inhibition. As parvalbumin- and cholecystokinin-expressing interneurons mediate distinct features of pyramidal cell activity4-6, the SCG2-dependent reorganization of inhibitory synaptic input might be predicted to affect network function in vivo. Consistent with this prediction, hippocampal gamma rhythms and pyramidal cell coupling to theta phase are significantly altered in the absence of Scg2. These findings reveal an instructive role for FOS and SCG2 in establishing a network of Fos-activated neurons via the rewiring of local inhibition to form a selectively modulated state. The opposing plasticity mechanisms acting on distinct inhibitory pathways may support the consolidation of memories over time.

Selective activation of the right hippocampus during navigation by spatial cues in domestic chicks (Gallus gallus).

In different vertebrate species, hippocampus plays a crucial role for spatial orientation. However, even though cognitive lateralization is widespread in the animal kingdom, the lateralization of this hippocampal function has been poorly studied. The aim of the present study was to investigate the lateralization of hippocampal activation in domestic chicks, during spatial navigation in relation to free-standing objects. Two groups of chicks were trained to find food in one of the feeders located in a large circular arena. Chicks of one group solved the task using the relational spatial information provided by free-standing objects present in the arena, while the other group used the local appearance of the baited feeder as a beacon. The immediate early gene product c-Fos was employed to map neural activation of hippocampus and medial striatum of both hemispheres. Chicks that used spatial cues for navigation showed higher activation of the right hippocampus compared to chicks that oriented by local features and compared to the left hippocampus. Such differences between the two groups were not present in the left hippocampus or in the medial striatum. Relational spatial information seems thus to be selectively processed by the right hippocampus in domestic chicks. The results are discussed in light of existing evidence of hippocampal lateralization of spatial processing in chicks, with particular attention to the contrasting evidence found in pigeons.