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Animals in the natural world constantly encounter geometrically complex landscapes. Successful navigation requires that they understand geometric features of these landscapes, including boundaries, landmarks, corners and curved areas, all of which collectively define the geometry of the environment 1-12 . Crucial to the reconstruction of the geometric layout of natural environments are concave and convex features, such as corners and protrusions. However, the neural substrates that could underlie the perception of concavity and convexity in the environment remain elusive. Here we show that the dorsal subiculum contains neurons that encode corners across environmental geometries in an allocentric reference frame. Using longitudinal calcium imaging in freely behaving mice, we find that corner cells tune their activity to reflect the geometric properties of corners, including corner angles, wall height and the degree of wall intersection. A separate population of subicular neurons encode convex corners of both larger environments and discrete objects. Both corner cells are non-overlapping with the population of subicular neurons that encode environmental boundaries. Furthermore, corner cells that encode concave or convex corners generalize their activity such that they respond, respectively, to concave or convex curvatures within an environment. Together, our findings suggest that the subiculum contains the geometric information needed to reconstruct the shape and layout of naturalistic spatial environments., (© 2024. The Author(s).)

Navigation is often constrained to pathways, and a recurring problem concerns whether to turn left or right when approaching an intersection. We examined this problem during T-maze performance in which the maze location in the recording environment varied over five-trial blocks and analyzed the associated positional firing patterns of hippocampal CA1 and posterior parietal cortex neurons. An arbitrary partitioning of the environmental space determined the left versus right turning rule for T-maze behavior. Under these conditions, rats learned the logical fragmentation of allocentric space into left turn and right turn sub-regions. Paradoxically, under these conditions, the spatial tuning of both posterior parietal cortex and hippocampal CA1 neurons followed the frame of reference given by the T-maze, as opposed to the location in the environment. Moreover, first trials within each block were associated with distinct firing rate changes for both posterior parietal cortex and hippocampal CA1 neurons. These data support a model where spatial tuning by hippocampus and cortex can interact to guide choice behavior in complex, path-based environments where a correct turn choice varies across environmental locations, and as a function of recent experience., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) causes progressive age-related defects in memory and cognitive function and has emerged as a major health and socio-economic concern in the US and worldwide. To develop effective therapeutic treatments for AD, we need to better understand the neural mechanisms by which AD causes memory loss and cognitive deficits. Here we examine large-scale hippocampal neural population calcium activities imaged at single cell resolution in a triple-transgenic Alzheimer's disease mouse model (3xTg-AD) that presents both amyloid plaque and neurofibrillary pathological features along with age-related behavioral defects. To measure encoding of environmental location in hippocampal neural ensembles in the 3xTg-AD mice in vivo, we performed GCaMP6-based calcium imaging using head-mounted, miniature fluorescent microscopes ("miniscopes") on freely moving animals. We compared hippocampal CA1 excitatory neural ensemble activities during open-field exploration and track-based route-running behaviors in age-matched AD and control mice at young (3-6.5 months old) and old (18-21 months old) ages. During open-field exploration, 3xTg-AD CA1 excitatory cells display significantly higher calcium activity rates compared with Non-Tg controls for both the young and old age groups, suggesting that in vivo enhanced neuronal calcium ensemble activity is a disease feature. CA1 neuronal populations of 3xTg-AD mice show lower spatial information scores compared with control mice. The spatial firing of CA1 neurons of old 3xTg-AD mice also displays higher sparsity and spatial coherence, indicating less place specificity for spatial representation. We find locomotor speed significantly modulates the amplitude of hippocampal neural calcium ensemble activities to a greater extent in 3xTg-AD mice during open field exploration. Our data offer new and comprehensive information about age-dependent neural circuit activity changes in this important AD mouse model and provide strong evidence that spatial coding defects in the neuronal population activities are associated with AD pathology and AD-related memory behavioral deficits., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In place of continuous overhead satellite views of an environment, the brain often relies on first-person experiences to estimate spatial relationships between locations. Using new methods, a recent study has found the spatial metric observed in hippocampal activity adapts to encode local environmental terrain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recent anatomical evidence suggests a functionally significant back-projection pathway from the subiculum to the CA1. Here we show that the afferent circuitry of CA1-projecting subicular neurons is biased by inputs from CA1 inhibitory neurons and the visual cortex, but lacks input from the entorhinal cortex. Efferents of the CA1-projecting subiculum neurons also target the perirhinal cortex, an area strongly implicated in object-place learning. We identify a critical role for CA1-projecting subicular neurons in object-location learning and memory, and show that this projection modulates place-specific activity of CA1 neurons and their responses to displaced objects. Together, these experiments reveal a novel pathway by which cortical inputs, particularly those from the visual cortex, reach the hippocampal output region CA1. Our findings also implicate this circuitry in the formation of complex spatial representations and learning of object-place associations.

Retrosplenial cortex (RSC) is heavily interconnected with a multitude of cortical regions and is directly connected with the hippocampal formation. As such, it is a likely coordinator of information transfer between the hippocampus (HPC) and cortex in the service of spatial cognition and episodic memory. The current work examined three potential temporal frameworks for retrosplenial-hippocampal communication, namely, theta frequency oscillations (6-12 Hz), sharp-wave/ripple events, and repeating, theta phase-locked shifts from low (30-65 Hz) to high (120-160 Hz) gamma frequency oscillations. From simultaneous recordings of single units and local field potentials (LFPs) in RSC and HPC, we report the presence of prominent theta, low-gamma, and high-gamma oscillations in the retrosplenial LFP. Retrosplenial and hippocampal theta rhythms were strongly coherent and subgroups of retrosplenial neurons exhibited either spiking at theta frequencies and/or spike-phase-locking to theta. Retrosplenial neurons were also phase-locked to local low- and high-gamma rhythms, and power in these frequency bands was coupled in a sequential fashion to specific phases of hippocampal and retrosplenial theta rhythms. Coordinated activity between the two regions also occurred during hippocampal sharp-wave/ripple events, where retrosplenial neuron populations were modulated in their spiking and retrosplenial LFPs exhibited sharp-wave-like events that co-occurred with those observed in HPC. These results identify several temporal windows of synchronization between RSC and HPC that may mediate cortico-hippocampal processes related to learning, memory, and spatial representation. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Flexible navigation demands knowledge of boundaries, routes and their relationships. Within a multi-path environment, a subpopulation of subiculum neurons robustly encoded the axis of travel. The firing of axis-tuned neurons peaked bimodally, at head orientations 180° apart. Environmental manipulations showed these neurons to be anchored to environmental boundaries but to lack axis tuning in an open arena. Axis-tuned neurons thus provide a powerful mechanism for mapping relationships between routes and the larger environmental context.

Similarities and differences in the visual content, scale, and shape of environmental boundaries for two environments have been extensively examined for their impact on the recurrence of spatially specific hippocampal firing patterns across environments and across multiple regions of a single environment. Although the shapes of paths taken through an environment are known to impact hippocampal firing patterns within any single region of a single environment, it is not known to what extent path shape and scale can impact firing pattern recurrence across two environments and across multiple regions of a single environment. This question was addressed in the present work where the spatial firing patterns of hippocampal CA1 neurons were examined as rats traversed differently shaped spiral paths centered on the same position within a visually observable curtained enclosure. On such tracks, firing fields for CA1 neurons were found to recur across multiple subregions of a single path and across similarly positioned regions of different paths. Both within and across different spiral tracks, the extent of such pattern recurrence was strongly influenced by similarity in the specific sequences of movement directions and locomotor behaviors engendered by different path shapes. The findings demonstrate that the shapes of paths taken through an environment can robustly and dynamically alter both the scale of spatially specific CA1 firing fields and the extent to which they recur across environments.

The spike discharge of hippocampal excitatory principal cells, also called "place cells," is highly location specific, but the discharge of local inhibitory interneurons is thought to display relatively low spatial specificity. Whereas in other brain regions, such as sensory neocortex, the activity of interneurons is often exquisitely stimulus selective and directly determines the responses of neighboring excitatory neurons, the activity of hippocampal interneurons typically lacks the requisite specificity needed to shape the defined structure of principal cell fields. Here we show that hippocampal formation interneurons have "on" fields (abrupt increases in activity) and "off" fields (abrupt decreases in activity) that are associated with the same location-specific informational content, spatial resolution, and dependency on context as the "place fields" of CA1 principal cells. This establishes that interneurons have well-defined place fields, thus having important implications for understanding how the hippocampus represents spatial information.

Previous research has revealed that the functional components of spatial cognition are lateralized in the forebrain of birds, including the hippocampal formation (HF). To investigate how HF cells in the left and right avian brain may differentially participate in representations of space, we recorded single-units from the HF of homing pigeons as they ran a plus maze for food. The rate maps of left HF cells often displayed elongated regions of increased activity in the center of the maze and along the maze corridors, whereas right HF cells tended to display patches at the ends of maze arms at/near goal locations. Left HF cells displayed a higher degree of spatial-specificity compared with right HF cells, including higher patch-specificity, higher reliability, and a higher incidence of location-correlated activity. Analysis of speed-correlated and trajectory-dependent activity also revealed significant HF-lateralized differences. Right HF cells tended to display significant negative correlations between spike rate and speed, although speed-dependent rate maps indicate that this relationship did not explain their space-specific activity. Left HF cells displayed a significantly higher incidence of trajectory-dependent space-specific activity than was observed in the right HF, suggesting that left HF cells may participate in navigating among goal locations. Differences in the correlates of left and right pigeon HF cells are consistent with unilateral HF-lesion data suggesting that the functional components of spatial cognition are lateralized in the avian brain, and furthermore, provide a basis for hypotheses regarding how the left and right HF support different aspects of spatial cognition., (Copyright 2005 Wiley-Liss, Inc.)

Analyzing neural dynamics underlying complex behavior is a major challenge in systems neurobiology. To meet this challenge through computational neuroscience, we have constructed a brain-based device (Darwin X) that interacts with a real environment, and whose behavior is guided by a simulated nervous system incorporating detailed aspects of the anatomy and physiology of the hippocampus and its surrounding regions. Darwin X integrates cues from its environment to solve a spatial memory task. Place-specific units, similar to place cells in the rodent, emerged by integrating visual and self-movement cues during exploration without prior assumptions in the model about environmental inputs. Because synthetic neural modeling using brain-based devices allows recording from all elements of the simulated nervous system during behavior, we were able to identify different functional hippocampal pathways. We did this by tracing back from reference neuronal units in the CA1 region of the simulated hippocampus to all of the synaptically connected units that were coactive during a particular exploratory behavior. Our analysis identified a number of different functional pathways within the simulated hippocampus that incorporate either the perforant path or the trisynaptic loop. Place fields, which were activated by the trisynaptic circuit, tended to be more selective and informative. However, place units that were activated by the perforant path were prevalent in the model and were crucial for generating appropriate exploratory behavior. Thus, in the model, different functional pathways influence place field activity and, hence, behavior during navigation.

We describe Darwin X, a physical device that interacts with a real environment, whose behavior is guided by a simulated nervous system incorporating aspects of the detailed anatomy and physiology of the hippocampus and its surrounding regions. This brain-based device integrates cues from its environment and solves a spatial memory task. The responses of simulated neuronal units in the hippocampal areas during its exploratory behavior are comparable to place cells in the rodent hippocampus and emerged by associating sensory cues during exploration. To identify different functional hippocampal pathways and their influence on behavior, we employed a time series analysis that distinguishes causal interactions within and between simulated hippocampal and neocortical regions while the device is engaged in a spatial memory task. Our analysis identified different functional pathways within the neural simulation and prompts novel predictions about the influence of the perforant path, the trisynaptic loop and hippocampal-cortical interactions on place cell activity and behavior during navigation. Moreover, this causal time series analysis may be useful in analyzing networks in general.

The importance of space-specific single-unit activity for hippocampal formation (HF)-mediated learning and memory in rodents has been extensively studied, yet little is known about how the unit findings in rodents generalize to other vertebrate species. We report a first assessment of the space-specific single-unit activity recorded from the HF of homing pigeons as they moved through a plus maze for food reward. Rate maps of pigeon HF single-unit activity typically revealed multiple regions (2-5 per cell) of increased activity (on average, 2.5 times higher than other regions of the maze) that in 27% of slow-firing cells was reliably space-specific over time. The qualitative appearance of rate maps and the degree of spatial-specificity observed for most all pigeon HF cells suggests more modest space-specific activity than typically reported for rat hippocampal cells. The nature of space-specific activity in the pigeon HF includes (1) often transiently reliable regions of increased activity for many cells, (2) multiple patches of activity that were sometimes observed in analogous maze areas, and (3) cells displaying substantial decreases in firing rate between baseline and maze-run conditions that could not be explained by a simple relationship between firing rate and a pigeon's speed. These observations suggest that pigeon HF cells may be coding for an unspecified behavioral/motivational/environmental factors in addition to a pigeon's momentary location. The data further suggest that the spatial ecology and evolutionary history of different species may be a critical feature shaping how HF neurons capture properties of space., (Copyright (c) 2004 Wiley-Liss, Inc.)

Electrophysiological activity was recorded from single neurons (units) in the hippocampal formation (HF) of freely moving homing pigeons in order to provide a taxonomy of unit types found in the avian HF; a taxonomy that could be used to define regional subdivisions and be compared with unit types found in the mammalian hippocampus. Two distinct types of unit were observed in the avian HF. One type was uniformly characterized by relatively rapid firing rates and shorter spike widths, and was found throughout the HF. The other type was more variable in activity profile but, compared with the fast-firing units, was characterized by slower firing rates and longer spike widths. However, despite the variable nature of the slow-firing units, most slow-firing units recorded within a given anatomical region displayed similar firing rates, spike widths, and interspike intervals. In general, ventral HF units displayed activity patterns similar to projection cells found in the mammalian Ammon's horn. Most dorsocaudal units displayed activity patterns similar to presumed granular cells in the mammalian dentate gyrus. By contrast, most dorsorostral units displayed activity patterns similar to a type of unit found in the mammalian subiculum. Although different in some details, the overall activity profile of units found in the avian HF, and their regional distribution, is strikingly similar to unit types found in the mammalian hippocampus, suggesting that unit activity profile is one hippocampal dimension conserved through evolution., (Copyright 2002 Wiley-Liss, Inc.)

A key challenge in developing diagnosis and treatments for Alzheimer's disease (AD) is to detect abnormal network activity at as early a stage as possible. To date, behavioral and neurophysiological investigations in AD model mice have yet to conduct a longitudinal assessment of cellular pathology, memory deficits, and neurophysiological correlates of neuronal activity. We therefore examined the temporal relationships between pathology, neuronal activities and spatial representation of environments, as well as object location memory deficits across multiple stages of development in the 5xFAD mice model and compared these results to those observed in wild-type mice. We performed longitudinal in vivo calcium imaging with miniscope on hippocampal CA1 neurons in behaving mice. We find that 5xFAD mice show amyloid plaque accumulation, depressed neuronal calcium activity during immobile states, and degenerate and unreliable hippocampal neuron spatial tuning to environmental location at early stages by 4 months of age while their object location memory (OLM) is comparable to WT mice. By 8 months of age, 5xFAD mice show deficits of OLM, which are accompanied by progressive degradation of spatial encoding and, eventually, impaired CA1 neural tuning to object-location pairings. Furthermore, depressed neuronal activity and unreliable spatial encoding at early stage are correlated with impaired performance in OLM at 8-month-old. Our results indicate the close connection between impaired hippocampal tuning to object-location and the presence of OLM deficits. The results also highlight that depressed baseline firing rates in hippocampal neurons during immobile states and unreliable spatial representation precede object memory deficits and predict memory deficits at older age, suggesting potential early opportunities for AD detecting.

Alzheimer's disease (AD) causes progressive age-related defects in memory and cognitive function and has emerged as a major health and socio-economic concern in the US and worldwide. To develop effective therapeutic treatments for AD, we need to better understand the neural mechanisms by which AD causes memory loss and cognitive deficits. Here we examine large-scale hippocampal neural population calcium activities imaged at single cell resolution in a triple-transgenic Alzheimer's disease mouse model (3xTg-AD) that presents both amyloid plaque and neurofibrillary pathological features along with age-related behavioral defects. To measure encoding of environmental location in hippocampal neural ensembles in the 3xTg-AD mice in vivo, we performed GCaMP6-based calcium imaging using head-mounted, miniature fluorescent microscopes ("miniscopes") on freely moving animals. We compared hippocampal CA1 excitatory neural ensemble activities during open-field exploration and track-based route-running behaviors in age-matched AD and control mice at young (3-6.5 months old) and old (18-21 months old) ages. During open-field exploration, 3xTg-AD CA1 excitatory cells display significantly higher calcium activity rates compared with Non-Tg controls for both the young and old age groups, suggesting that in vivo enhanced neuronal calcium ensemble activity is a disease feature. CA1 neuronal populations of 3xTg-AD mice show lower spatial information scores compared with control mice. The spatial firing of CA1 neurons of old 3xTg-AD mice also displays higher sparsity and spatial coherence, indicating less place specificity for spatial representation. We find locomotor speed significantly modulates the amplitude of hippocampal neural calcium ensemble activities to a greater extent in 3xTg-AD mice during open field exploration. Our data offer new and comprehensive information about age-dependent neural circuit activity changes in this important AD mouse model and provide strong evidence that spatial coding defects in the neuronal population activities are associated with AD pathology and AD-related memory behavioral deficits.

The hippocampal formation (HF) is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the HF, but the circuit connectivity across septal to temporal regions is less well described. The emergence of viral genetic mapping techniques enhances our ability to determine the detailed complexity of HF circuitry. In earlier work, we mapped a subiculum (SUB) back projection to CA1 prompted by the discovery of theta wave back propagation from the SUB to CA1 and CA3. We reason that this circuitry may represent multiple extended noncanonical pathways involving the subicular complex and hippocampal subregions CA1 and CA3. In the present study, multiple retrograde viral tracing approaches produced robust mapping results, which supports this prediction. We find significant noncanonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1 (vCA1), perirhinal cortex (Prh), and the subicular complex. Thus, CA1 inputs to CA3 run opposite the trisynaptic pathway and in a temporal to septal direction. Our retrograde viral tracing results are confirmed by anterograde-directed viral mapping of projections from input mapped regions to hippocampal dorsal CA3 (dCA3). We find that genetic inactivation of the projection of vCA1 to dCA3 impairs object-related spatial learning and memory but does not modulate anxiety-related behaviors. Our data provide a circuit foundation to explore novel functional roles contributed by these noncanonical hippocampal circuit connections to hippocampal circuit dynamics and learning and memory behaviors.

Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

Physiological studies suggest spatial representation gradients along the CA1 proximodistal axis. To determine the underlying anatomical basis, we quantitatively mapped canonical and noncanonical inputs to excitatory neurons in dorsal hippocampal CA1 along the proximal-distal axis in mice of both sexes using monosynaptic rabies tracing. Our quantitative analyses show comparable strength of subiculum complex and entorhinal cortex (EC) inputs to CA1, significant inputs from presubiculum and parasubiculum to CA1, and a threefold stronger input to proximal versus distal CA1 from CA3. Noncanonical subicular complex inputs exhibit opposing topographic connectivity gradients whereby the subiculum-CA1 input strength systematically increases but the presubiculum-CA1 input strength decreases along the proximal-distal axis. The subiculum input strength cotracks that of the lateral EC, known to be less spatially selective than the medial EC. The functional significance of this organization is verified physiologically for subiculum-to-CA1 inputs. These results reveal a novel anatomical framework by which to determine the circuit bases for CA1 representations.

Learning to ignore irrelevant stimuli is essential to achieving efficient and fluid attention, and serves as the complement to increasing attention to relevant stimuli. The different cholinergic (ACh) subsystems within the basal forebrain regulate attention in distinct but complementary ways. ACh projections from the substantia innominata/nucleus basalis region (SI/nBM) to the neocortex are necessary to increase attention to relevant stimuli and have been well studied. Lesser known are ACh projections from the medial septum/vertical limb of the diagonal band (MS/VDB) to the hippocampus and the cingulate that are necessary to reduce attention to irrelevant stimuli. We developed a neural simulation to provide insight into how ACh can decrement attention using this distinct pathway from the MS/VDB. We tested the model in behavioral paradigms that require decremental attention. The model exhibits behavioral effects such as associative learning, latent inhibition, and persisting behavior. Lesioning the MS/VDB disrupts latent inhibition, and drastically increases perseverative behavior. Taken together, the model demonstrates that the ACh decremental pathway is necessary for appropriate learning and attention under dynamic circumstances and suggests a canonical neural architecture for decrementing attention.

The hippocampus and posterior parietal cortex are implicated in both episodic memory and encoding of position in an environment. In the present study, we examine the impact of locomotor behaviors associated with movement in both the horizontal and vertical dimensions on population activity patterns in these two brain structures. We utilized a five‐looped, squared spiral track containing stair segments, ramp segments, and flat segments. In addition to encoding locations along the full route, posterior parietal cortex population activity demonstrates strong pattern recurrence for similar action types at different locations in the environment. Additionally, posterior parietal and hippocampal neurons exhibit parallel modulation in the scale of representation that follows behavioral dynamics required for track traversal. These findings build on prior work examining spatial mapping in the vertical dimension and provide a better understanding of how a series of actions and visited locations can be coordinated in the generation of episodic memory. [ABSTRACT FROM AUTHOR]

Self-motion information influences spatially-specific firing patterns exhibited by hippocampal neurons. Moreover, these firing patterns can repeat across similar subsegments of an environment, provided that there is similarity of path shape and head orientations across subsegments. The influence of self-motion variables on repeating fields remains to be determined. To investigate the role of path shape and angular rotation on hippocampal activity, we recorded the activity of CAI neurons from rats trained to run on spiral-shaped tracks. During inbound traversais of circular-spiral tracks, angular velocity increases continuously. Under this condition, most neurons (74%) exhibited repeating fields across at least three adjacent loops. Of these neurons, 86% exhibited forward shifts in the angles of field centers relative to centers on preceding loops. Shifts were absent on squared-spiral tracks, minimal and less reliable on concentric-circle tracks, and absent on outward-bound runs on circular-spiral tracks. However, outward-bound runs on the circular-spiral track in the dark were associated with backward shifts. Together, the most parsimonious interpretation of the results is that continuous increases or decreases in angular velocity are particularly effective at shifting the center of mass of repeating fields, although it is also possible that a nonlinear integration of step counts contributes to the shift. Furthermore, the unexpected absence of field shifts during outward journeys in light (but not darkness) suggests visual cues around the goal location anchored the map of space to an allocentric reference frame. [ABSTRACT FROM AUTHOR]

Abstract: The registration of spatial information by neurons of the parietal cortex takes on many forms. In most experiments, spatially modulated parietal activity patterns are found to take as their frame of reference some part of the body such as the retina. However, recent findings obtained in single neuron recordings from both rat and monkey parietal cortex suggest that the frame of reference utilized by parietal cortex may also be abstract or arbitrary in nature. Evidence in rats comes from work indicating that parietal activity in freely behaving rodents is organized according to the space defined by routes taken through an environment. In monkeys, evidence for an object-centered frame of reference has recently been presented. The present work reviews single neuron recording experiments in parietal cortex of freely behaving rats and considers the potential contribution of parietal cortex in solving navigational tasks. It is proposed that parietal cortex, in interaction with the hippocampus, plays a critical role in the selection of the most appropriate route between two points and, in addition, produces a route-based positional signal capable of guiding sensorimotor transitions. [Copyright &y& Elsevier]

Summary Traversal of a complicated route is often facilitated by considering it as a set of related sub-spaces. Such compartmentalization processes could occur within retrosplenial cortex, a structure whose neurons simultaneously encode position within routes and other spatial coordinate systems. Here, retrosplenial cortex neurons were recorded as rats traversed a track having recurrent structure at multiple scales. Consistent with a major role in compartmentalization of complex routes, individual retrosplenial cortex (RSC) neurons exhibited periodic activation patterns that repeated across route segments having the same shape. Concurrently, a larger population of RSC neurons exhibited single-cycle periodicity over the full route, effectively defining a framework for encoding of sub-route positions relative to the whole. The same population simultaneously provides a novel metric for distance from each route position to all others. Together, the findings implicate retrosplenial cortex in the extraction of path sub-spaces, the encoding of their spatial relationships to each other, and path integration. [ABSTRACT FROM AUTHOR]