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•Better memory and boundary processing during navigation in young vs. older adults.•Age × intervention interaction in medial temporal lobe activity.•L-DOPA enhanced boundary processing and spatial learning associated in older adults.•L-DOPA impaired young adults’ memory performance during spatial navigation.•Overall, L-DOPA improved location-cue processing relative to boundary processing. Aging is associated with changes in spatial navigation behavior. In addition to an overall performance decline, older adults tend to rely more on proximal location cue information than on environmental boundary information during spatial navigation compared to young adults. The fact that older adults are more susceptible to errors during spatial navigation might be partly attributed to deficient dopaminergic modulation of hippocampal and striatal functioning. Hence, elevating dopamine levels might differentially modulate spatial navigation and memory performance in young and older adults. In this work, we administered levodopa (L-DOPA) in a double-blind within-subject, placebo-controlled design and recorded functional neuroimaging while young and older adults performed a 3D spatial navigation task in which boundary geometry or the position of a location cue were systematically manipulated. An age by intervention interaction on the neural level revealed an upregulation of brain responses in older adults and a downregulation of responses in young adults within the medial temporal lobe (including hippocampus and parahippocampus) and brainstem, during memory retrieval. Behaviorally, L-DOPA had no effect on older adults’ overall memory performance; however, older adults whose spatial memory improved under L-DOPA also showed a shift towards more boundary processing under L-DOPA. In young adults, L-DOPA induced a decline in spatial memory performance in task-naïve participants. These results are consistent with the inverted-U-shaped hypothesis of dopamine signaling and cognitive function and suggest that increasing dopamine availability improves hippocampus-dependent place learning in some older adults.

Previous studies indicate a role of dopamine in spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a dopamine precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved across all regions following L-DOPA administration, suggesting that dopamine broadly enhances neural representations of direction. No evidence for differences between regions was found. In the hippocampus these results were found in both age groups, while in the retrosplenial cortex they were only observed in younger adults. Taken together, our study provides evidence for a link between dopamine and the specificity of neural responses during spatial navigation. The sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someone’s true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

Broad individual differences exist in the ability to create a cognitive map of a new environment. The current studies investigated whether familiarizing participants with to-be-learned target landmarks (Experiment 1) or target landmarks plus the order they would be encountered along routes (Experiment 2) before exploring the Silcton virtual environment would increase performance on tasks assaying spatial memory of Silcton. Participants in both experiments were randomly assigned to be pre-exposed either to information about target landmarks in Silcton or control landmarks on the university campus. In both experiments, participants explored Silcton via four prescribed routes and then performed a direction estimation task and a map building task based on memory for the locations of the target landmarks. In addition, participants completed the Spatial Orientation Test of perspective-taking. Pre-exposure to Silcton landmarks versus control landmarks did not affect scores on Silcton-based tasks in either experiment. Some sex differences in direction estimation were observed in Experiment 1 but not Experiment 2. While facilitating familiarity with landmarks did not improve cognitive map accuracy, both sex and perspective taking ability were found to contribute to individual differences in the ability to create a cognitive map. On relève d'importantes différences individuelles dans la capacité à créer une carte cognitive d'un nouvel environnement. Les études en cours ont examiné si le fait de familiariser les participants avec des points de repère cibles à apprendre (Expérience 1) ou avec des points de repère cibles en spécifiant l'ordre dans lequel ils seraient rencontrés le long des routes (Expérience 2) avant d'explorer l'environnement virtuel de Silcton pouvait améliorer les performances relativement à des tâches de mémoire spatiale de Silcton. Les participants des deux expériences ont été choisis au hasard pour être préexposés soit à l'information sur les points de repère cibles de Silcton ou à celle des points de repère de contrôle sur le campus de l'université. Dans les deux expériences, les participants ont exploré Silcton selon quatre routes imposées, puis effectué une tâche d'estimation de la direction et une tâche de production d'une carte en se basant sur leur mémoire des emplacements des points de repère cibles. Les participants ont également suivi le test d'orientation spatiale en matière de prise de perspective. Une préexposition aux points de repère de Silcton par rapport à des points de repère de contrôle n'a pas affecté les résultats des tâches basées sur Silcton dans ni l'une ni l'autre des expériences. Certaines des différences au niveau du sexe dans l'estimation de la direction ont été notées dans l'Expérience 1 mais pas dans l'expérience 2. Alors que le fait de faciliter la familiarité avec des points de repère n'a pas amélioré la précision des cartes cognitives, le sexe et la capacité à prendre une perspective ont tous les deux contribué aux différences individuelles en termes de capacité à créer une carte cognitive. Public Significance Statement Individual differences in the ability to create a mental map of a novel environment have been demonstrated in the laboratory, but their origins are not well understood. It is possible that familiarizing individuals with the buildings and the routes in a new environment before they experience it may help them form a mental map. Such pretraining did not facilitate the accuracy of mental representations, and it seems likely that variation in spatial visualization abilities is a larger contributor to individual differences in mental map accuracy.

Flexible behaviors over long timescales are thought to engage recurrent neural networks in deep brain regions, which are experimentally challenging to study. In insects, recurrent circuit dynamics in a brain region called the central complex (CX) enable directed locomotion, sleep, and context- and experience-dependent spatial navigation. We describe the first complete electron microscopy-based connectome of the Drosophila CX, including all its neurons and circuits at synaptic resolution. We identified new CX neuron types, novel sensory and motor pathways, and network motifs that likely enable the CX to extract the fly’s head direction, maintain it with attractor dynamics, and combine it with other sensorimotor information to perform vector-based navigational computations. We also identified numerous pathways that may facilitate the selection of CX-driven behavioral patterns by context and internal state. The CX connectome provides a comprehensive blueprint necessary for a detailed understanding of network dynamics underlying sleep, flexible navigation, and state-dependent action selection.

Ever since Tolman's proposal of cognitive maps in the 1940s, the question of how spatial representations support flexible behavior has been a contentious topic. Bellmund et al. review and combine concepts from cognitive science and philosophy with findings from neurophysiology of spatial navigation in rodents to propose a framework for cognitive neuroscience. They argue that spatial-processing principles in the hippocampalentorhinal region provide a geometric code to map information domains of cognitive spaces for high-level cognition and discuss recent evidence for this proposal. Science , this issue p. eaat6766 The hippocampal formation has long been suggested to underlie both memory formation and spatial navigation. We discuss how neural mechanisms identified in spatial navigation research operate across information domains to support a wide spectrum of cognitive functions. In our framework, place and grid cell population codes provide a representational format to map variable dimensions of cognitive spaces. This highly dynamic mapping system enables rapid reorganization of codes through remapping between orthogonal representations across behavioral contexts, yielding a multitude of stable cognitive spaces at different resolutions and hierarchical levels. Action sequences result in trajectories through cognitive space, which can be simulated via sequential coding in the hippocampus. In this way, the spatial representational format of the hippocampal formation has the capacity to support flexible cognition and behavior.

The neural systems supporting scene-perception and spatial-memory systems of the human brain are well-described. But how do these neural systems interact? Here, using fine-grained individual-subject fMRI, we report three cortical areas of the human brain, each lying immediately anterior to a region of the scene perception network in posterior cerebral cortex, that selectively activate when recalling familiar real-world locations. Despite their close proximity to the scene-perception areas, network analyses show that these regions constitute a distinct functional network that interfaces with spatial memory systems during naturalistic scene understanding. These “place-memory areas” offer a new framework for understanding how the brain implements memory-guided visual behaviors, including navigation. Navigation requires integration of visual information with spatial memory representations. Steel et al. describe a new network of brain areas that facilitates the interaction between these perceptual and mnemonic neural systems.

Many behavioural tasks require the manipulation of mathematical vectors, but, outside of computational models 1 – 7 , it is not known how brains perform vector operations. Here we show how the Drosophila central complex, a region implicated in goal-directed navigation 7 – 10 , performs vector arithmetic. First, we describe a neural signal in the fan-shaped body that explicitly tracks the allocentric travelling angle of a fly, that is, the travelling angle in reference to external cues. Past work has identified neurons in Drosophila 8 , 11 – 13 and mammals 14 that track the heading angle of an animal referenced to external cues (for example, head direction cells), but this new signal illuminates how the sense of space is properly updated when travelling and heading angles differ (for example, when walking sideways). We then characterize a neuronal circuit that performs an egocentric-to-allocentric (that is, body-centred to world-centred) coordinate transformation and vector addition to compute the allocentric travelling direction. This circuit operates by mapping two-dimensional vectors onto sinusoidal patterns of activity across distinct neuronal populations, with the amplitude of the sinusoid representing the length of the vector and its phase representing the angle of the vector. The principles of this circuit may generalize to other brains and to domains beyond navigation where vector operations or reference-frame transformations are required. A neural circuit for implementing a coordinate transformation and 2D vector computation is described in Drosophila .

When faced with predatory threats, escape towards shelter is an adaptive action that offers long-term protection against the attacker. Animals rely on knowledge of safe locations in the environment to instinctively execute rapid shelter-directed escape actions 1 , 2 . Although previous work has identified neural mechanisms of escape initiation 3 , 4 , it is not known how the escape circuit incorporates spatial information to execute rapid flights along the most efficient route to shelter. Here we show that the mouse retrosplenial cortex (RSP) and superior colliculus (SC) form a circuit that encodes the shelter-direction vector and is specifically required for accurately orienting to shelter during escape. Shelter direction is encoded in RSP and SC neurons in egocentric coordinates and SC shelter-direction tuning depends on RSP activity. Inactivation of the RSP–SC pathway disrupts the orientation to shelter and causes escapes away from the optimal shelter-directed route, but does not lead to generic deficits in orientation or spatial navigation. We find that the RSP and SC are monosynaptically connected and form a feedforward lateral inhibition microcircuit that strongly drives the inhibitory collicular network because of higher RSP input convergence and synaptic integration efficiency in inhibitory SC neurons. This results in broad shelter-direction tuning in inhibitory SC neurons and sharply tuned excitatory SC neurons. These findings are recapitulated by a biologically constrained spiking network model in which RSP input to the local SC recurrent ring architecture generates a circular shelter-direction map. We propose that this RSP–SC circuit might be specialized for generating collicular representations of memorized spatial goals that are readily accessible to the motor system during escape, or more broadly, during navigation when the goal must be reached as fast as possible. The retrosplenial cortex and superior colliculus of mouse form a neural circuit that specifically encodes shelter location, facilitating rapid escape from predatory threats.

Cells in the hippocampal–entorhinal circuit, which fire in response to navigational variables such as location or speed, are shown also to encode continuous, task-relevant but non-spatial variables such as sound frequency. Mapping sound in the brain (Tank 21692, Bio Letter) Map-like representations of physical space have been well-documented in the hippocampus by studies of spatial navigation, but it is unclear whether this spatial representation is part of a more general mechanism for encoding other continuous variables, such as sound. Here, David Tank and colleagues recorded from rat hippocampal neurons while they manipulated a joystick to control sound output along a continuous frequency scale. Neurons encoded for all aspects of this task and formed discrete firing fields in response to specific sound frequencies. The hippocampal cells representing this auditory axis overlapped with cells representing space during navigation. The authors suggest that representation mechanisms similar to those used during navigation may encode variables in a broader range of cognitive processes. During spatial navigation, neural activity in the hippocampus and the medial entorhinal cortex (MEC) is correlated to navigational variables such as location 1 , 2 , head direction 3 , speed 4 , and proximity to boundaries 5 . These activity patterns are thought to provide a map-like representation of physical space. However, the hippocampal–entorhinal circuit is involved not only in spatial navigation, but also in a variety of memory-guided behaviours 6 . The relationship between this general function and the specialized spatial activity patterns is unclear. A conceptual framework reconciling these views is that spatial representation is just one example of a more general mechanism for encoding continuous, task-relevant variables 7 , 8 , 9 , 10 . Here we tested this idea by recording from hippocampal and entorhinal neurons during a task that required rats to use a joystick to manipulate sound along a continuous frequency axis. We found neural representation of the entire behavioural task, including activity that formed discrete firing fields at particular sound frequencies. Neurons involved in this representation overlapped with the known spatial cell types in the circuit, such as place cells and grid cells. These results suggest that common circuit mechanisms in the hippocampal–entorhinal system are used to represent diverse behavioural tasks, possibly supporting cognitive processes beyond spatial navigation.

Grid cells with their rigid hexagonal firing fields are thought to provide an invariant metric to the hippocampal cognitive map, yet environmental geometrical features have recently been shown to distort the grid structure. Given that the hippocampal role goes beyond space, we tested the influence of nonspatial information on the grid organization. We trained rats to daily learn three new reward locations on a cheeseboard maze while recording from the medial entorhinal cortex and the hippocampal CA1 region. Many grid fields moved toward goal location, leading to long-lasting deformations of the entorhinal map. Therefore, distortions in the grid structure contribute to goal representation during both learning and recall, which demonstrates that grid cells participate in mnemonic coding and do not merely provide a simple metric of space.