Hippocampus

Spatial memories are represented by hippocampal place cells during navigation. This spatial code is dynamic, undergoing changes across time - known as drift - and across changes in internal state, even while navigating the same spatial environment with consistent behavior. A dynamic spatial code may be a way for the hippocampus to track distinct episodes that occur at different times or during different internal states and update spatial memories. Changes to the spatial code include place fields that remap to new locations and place fields that vanish, while others are stable. However, what determines place field fate across episodes remains unclear. We measured the lap-by-lap properties of place cells in mice during navigation for a block of trials in a rewarded virtual environment. We then had mice navigate the same spatial environment for another block of trials either separated by a day (a distinct temporal episode) or during the same session but with reward removed to change reward expectation (a distinct internal state episode). We found that, as a population, place cells with remapped place fields across episodes had lower spatial precision during navigation in the initial episode. Place cells with stable or vanished place fields generally had higher spatial precision. We conclude that place cells with less precise place fields have greater spatial flexibility, allowing them to respond to, and track, distinct episodes in the same spatial environment, while place cells with precise place fields generally preserve spatial information when their fields reappear.

Spatial tuning is a hallmark property of neural firing in the hippocampal formation. Yet, that tuning is often less well correlated with the instantaneous current position of an animal than it is with an integrated version of the past or future state of the animal. Whether that encoding is biased towards past or future states and the extent to which it shows fixed versus multi-scale encoding varies across circuits and cell types. The temporal encoding properties of boundary vector cells of the subiculum are not well established. To address this here, we re-analyzed recordings of BVCs described previously by Lever et al. (2009) with multiple approaches. In the first, we asked if adding a temporal offset between the rat position and the spiking of a BVC increased the apparent spatial tuning in the firing rate map. We found that aligning BVC spiking with future states maximized the rate map spatial tuning. These results were mirrored in a second analysis that, instead of optimizing rate map spatial tuning, optimized how well the firing rate map predicted the BVC spiking. The second analysis also allowed us to ask whether that encoding is focused on a particular temporal horizon or whether the encoding captures behavior at multiple scales. To this end, for a given recording, we asked "How much time-integration of the behavioral state is the observed spiking most consistent with?" We observed a wide spectrum of time-constants of integration across cells, indicating that BVCs form a multiscale encoding of future states. The distribution of both offsets and integration rates observed across BVCs did not differ significantly from other, non-BVC, subiculum neurons. Taken together, these findings indicate that BVCs, along with other subiculum neurons, form a multi-scale encoding of future states.

The hippocampal formation is well documented as having a feedforward, unidirectional circuit organization termed the trisynaptic pathway. This circuit organization exists along the septotemporal axis of the hippocampal formation, 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 hippocampal formation circuitry. In earlier work, we mapped a subiculum back-projection to CA1 prompted by the discovery of theta wave back-propagation from the subiculum to CA1 and CA3. We reason that this circuitry may represent multiple extended non-canonical 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 non-canonical synaptic inputs to dorsal hippocampal CA3 from ventral CA1, perirhinal cortex, 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. Together, our data provide a circuit foundation to explore novel functional roles contributed by these non-canonical hippocampal circuit connections to hippocampal dynamics and behavior.

An internal representation of the environment - or map - allows animals to evaluate multiple routes and adapt their navigation strategy to current needs and future goals. The hippocampal formation plays a crucial role in learning a spatial map and using the map for goal-directed navigation. The lateral septum forms a major node for connections between the hippocampus and subcortical brain regions that could link the spatial map to motivation and reward processing centers such as the ventral tegmental area and hypothalamus. It is not known, however, how the lateral septum contributes to the processing of spatial information and route planning. In this study, we investigated the temporal dynamics of spatial representations in the lateral septum. Neuropixels probes were used to record cellular activity along the dorsal-ventral extent of the lateral septum while rats performed one of two spatial navigation tasks in a Y-maze. The activity of a large fraction of cells was theta rhythmic and a subset of cells showed evidence of being active on alternate theta cycles (theta cycle skipping). Both theta rhythmicity and cycle skipping were strongest in the dorsal lateral septum. Similarly, spatially selective firing was most prominent in the dorsal lateral septum. Using neural decoding, we show that the lateral septum cell population encodes both the current location and alternatingly the possible future paths within single theta cycles when rats approach the choice point in the maze. Our data further shows that the alternating expression of spatial representations in the lateral septum is task-dependent, such that it is strongest when the task also requires the animals to alternate between rewarded goal arms. These data suggest that task demands and experience shape which representations are activated near a choice point. The lateral septum receives strong input from hippocampal place cells, and while there may be integration and transformation of incoming spatial signals, our findings support the idea that hippocampal spatial representations and their temporal dynamics are conveyed to subcortical projection areas through the lateral septum.

Hippocampal function relies on the anterior thalamic nuclei, but the reasons remain poorly understood. While anterior thalamic lesions disrupt parahippocampal spatial signalling, their impact on the subiculum is unknown, despite the importance of this area for hippocampal networks. We recorded subicular cells in rats with either permanent (N-methyl-D-aspartic acid) or reversible (muscimol) anterior thalamic lesions. Bayesian and other statistical analyses underscored the notable absence of the diverse spatial signals normally found in the subiculum, including place cells, following permanent anterior thalamic lesions. Likewise, there was marked disruption of these diverse spatial signals during transient lesions. By contrast, permanent anterior thalamic lesions had no discernible impact on CA1 place fields. Anterior thalamic lesions reduced spatial alternation performance (permanently or reversibly) to chance, while leaving a non-spatial recognition memory task unaffected. These findings, which help explain why anterior thalamic damage is so deleterious for spatial memory, cast a new spotlight on the importance of subiculum function and reveal its dependence on anterior thalamic signalling. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=184 HEIGHT=200 SRC="FIGDIR/small/928762v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@9ae754org.highwire.dtl.DTLVardef@1c96837org.highwire.dtl.DTLVardef@1d91ddaorg.highwire.dtl.DTLVardef@136fa1d_HPS_FORMAT_FIGEXP M_FIG C_FIG

Recent long-term optical imaging studies have demonstrated that the activity levels of hippocampal neurons in a familiar environment change on a daily to weekly basis. However, it is unclear whether there is any time-invariant property in the cells neural representations. In this study, using miniature fluorescence microscopy, we measured the neural activity of the mouse hippocampus in four different environments every 3 days. Although the activity level of hippocampal neurons fluctuated greatly in each environment across days, we found a significant correlation between the activity levels for different days, and the correlation was higher for averaged activity levels across multiple environments. When the number of environments used for averaging was increased, a higher activity correlation was observed. Furthermore, the number of environments in which a cell showed activity was preserved. Cells that showed place cell activity in many environments had greater spatial information content, and thus carried a higher amount of information about the current position. In contrast, cells that were active only in a small number of environments provided sparse representation for the environment. These results suggest that each cell has not only an inherent activity level but also play a characteristic role in the coding of space. Significance StatementRecent studies have revealed that place cell activity in the hippocampal CA1 cells exhibit instability on a daily to weekly scale. However, it is unclear whether there is any invariant property in the activity of the cells. In this study, we found that, although the activity level of CA1 neurons fluctuated greatly in one environment, the mean activity level across multiple environments was more stable. Furthermore, the number of environments in which a cell showed activity was preserved over time. These results suggest that even though the spatial code changes dynamically, each cell has an inherent activity level and plays a characteristic role in spatial coding.

Hippocampal place cells form a map of an animals environment. When the animal moves to a new environment, place field locations and firing rates change, a phenomenon known as remapping. Different animals can have different remapping responses to the same environments. This variability across animals in remapping behavior is not well understood. In this work, we analyzed electrophysiological recordings from Alme et al. (2014), in which five male rats were exposed to 11 different environments. To compare the hippocampal maps in two rooms, we computed average rate map correlation coefficients. We discovered that the heterogeneity in animals remapping behavior is structured: animals remapping behavior is consistent across a range of independent comparisons. Our findings highlight that remapping behavior between repeated environments depends on animal-specific factors.

Hippocampal theta (6-12 Hz) oscillations coordinate neural activity during spatial navigation and are strongly related to locomotion speed. However, recent research has yielded conflicting evidence on whether theta rhythms are primarily modulated by acceleration or instantaneous speed. Moreover, the role of movement transitions--at locomotion onset and offset--has often been overlooked, despite potentially involving distinct dynamics not explained by speed or acceleration alone. Previous studies have rarely controlled for locomotion timing and speed, limiting our ability to dissociate the contributions of speed, acceleration, and movement transitions. To address this, we used a computer-controlled treadmill to induce rat locomotion under three distinct conditions: (a) movement transitions, (b) steady running at constant speed, and (c) locomotion with continuous acceleration. This setup allowed precise spectral analysis of hippocampal theta oscillations across conditions. We found that treadmill-triggered movement transitions produced sustained increases in theta power and transient increases in theta frequency. Upon treadmill stop, theta power decreased slowly, whereas theta frequency dropped rapidly. Steady running elevated both theta power and frequency relative to rest. During constant-speed trials, both metrics increased with speed and remained stable over time. Notably, the acceleration rate itself had no effect on theta power or frequency. Instead, during accelerating trials, theta frequency increased progressively with instantaneous speed, underscoring speed as the primary modulator. In summary, our results show that movement transitions induce distinct, sustained changes in theta power and transient changes in theta frequency, while instantaneous speed--not acceleration--governs hippocampal theta frequency. Significance statementThe precise contributions of movement transitions, speed, and acceleration to hippocampal theta oscillations remain unclear due to confounding factors in freely moving paradigms. To resolve this, we employed a computer-controlled treadmill to systematically isolate each locomotor variable under tightly controlled conditions. Our results demonstrate that movement transitions induce distinct changes in theta power and frequency, and that instantaneous speed--not acceleration--robustly modulates theta frequency across hippocampal subregions. These findings clarify an ongoing debate and refine our understanding of how specific locomotor dynamics shape hippocampal activity during navigation.

(Re)mapping of different environments by hippocampal place cells is thought to reflect incidental learning. Rat "head scanning" is a spontaneous and presumed investigatory behavior that can trigger the onset of firing locations in place cells. This behavior was studied on (quasi-)circular tracks, and it was speculated that off-track head scans might have been overlooked or inadvertently discouraged in studies employing more common apparatus. To better understand the general prevalence and significance of off-track scanning, we investigated it in rats running laps on linear tracks in rooms featuring visual landmarks. Scanning spanned the length of the track, even in highly familiar conditions and in rats rewarded only at the two ends of the track. Thus, co-localized rewards are not necessary for the occurrence of this behavior. Scanning rate increased markedly in a novel room and then declined steeply during each daily session in this room over 3 days. Transient increases at the beginning of each daily session partially counteracted this decline, producing a "seesaw" profile that is reminiscent of previous observations on place cell plasticity. Therefore, the remapping that place cells are known to undergo in similar contextual changes could conceivably be facilitated by the putative surge of new place fields induced by increased scanning. Investigatory behaviors could thus be causally involved in the representational and dynamic properties of hippocampal representations. Addressing these possibilities offers insight into the incidental creation and update of a cognitive map. HIGHLIGHTSO_LIRat head scanning is known to trigger the onset of firing locations in place cells C_LIO_LIOff-track scanning occurs on linear tracks in familiar and novel conditions C_LIO_LICo-localized rewards are not necessary for scanning events C_LIO_LIResponse to a novel room resembles that seen in place cell dynamics C_LIO_LIRelationships between head scanning and place field formation could help uncover the incidental process of map making C_LI

The dentate gyrus is critical for spatial memory formation and shows task related activation of cellular ensembles considered as memory engrams. Semilunar granule cells (SGCs), a sparse dentate projection neuron subtype distinct from granule cells (GCs), were recently reported to be enriched among behaviorally activated neurons. However, the mechanisms governing SGC recruitment during memory formation and their role in engram refinement remains unresolved. By examining neurons labeled during contextual memory formation in TRAP2 mice, we empirically tested competing hypotheses for GC and SGC recruitment into memory ensembles. In support of the proposal that more excitable neurons are preferentially recruited into memory ensembles, SGCs showed greater sustained firing than GCs. Additionally, SGCs labeled during memory formation showed less adapting firing than unlabeled SGCs. Our recordings did not reveal glutamatergic connections between behaviorally labeled SGCs and GCs, providing evidence against SGC driven local circuit feedforward excitation in ensemble recruitment. Contrary to a leading hypothesis, there was little evidence for individual SGCs or labeled neuronal ensembles supporting lateral inhibition of unlabeled neurons. Instead, labeled GCs and SGCs received more spontaneous excitatory synaptic inputs than their unlabeled counterparts. Moreover, pairs of GCs and SGCs within labeled neuronal cohorts received more temporally correlated spontaneous excitatory synaptic inputs than labeled-unlabeled neuronal pairs, validating a role for correlated afferent inputs in neuronal ensemble selection. These findings challenge the proposal that SGCs drive dentate GC ensemble refinement, while supporting a role for intrinsic active properties and correlated inputs in preferential SGC recruitment to contextual memory engrams. Impact StatementEvaluation of semilunar granule cell involvement in dentate gyrus contextual memory processing supports recruitment based on intrinsic and input characteristics while revealing limited contribution to ensemble refinement. Major subject area, keywords and organismsSemilunar granule cell, inhibition, memory, engram, circuit, hippocampus

Sharp-wave ripples (SWRs) are hippocampal network oscillations associated with memory consolidation. They are characterized by the co-occurrence of fast and slow field potentials across CA1 layers: the fast-frequency oscillations, known as ripples, are prominent in the pyramidal cell layer, where they coincide with increased neuronal spiking, while slower negative transients, referred to as sharp waves, occur simultaneously in the stratum radiatum. SWRs have traditionally been considered globally synchronous across the hippocampus; however, recent evidence suggests that ripples may be less synchronous than previously thought, particularly between the two hemispheres (Villalobos et al., 2017). In this study, we revisited this question using a unique dataset from probes spanning the septotemporal axis of CA1. Our results demonstrate that ripples are phase-locked within but not between hemispheres, although their occurrence remains time-locked across both the septo-temporal axis and hemispheres. We also observed a similar synchronicity pattern for spiking activity: neurons are locally phase-coupled and globally time-coupled to ripple events. Interneurons exhibit a much stronger phase coupling to both ipsilateral and contralateral ripples than pyramidal neurons. These findings suggest that ripples are locally phase-coupled through pyramidal-interneuron interactions, with global time-locking likely driven by a common bilateral CA3 input and potentially modulated by interneuron circuits.

Mitochondrial morphology varies by neuronal cell type and subcellular compartment; however, the functional significance of these differences is unclear. Hippocampal CA2 neurons are enriched for genes encoding mitochondrial proteins compared to CA1 neurons, suggesting a difference in metabolic demand across hippocampal circuits. However, whether CA2 neuron mitochondria are structurally or functionally distinct to support circuit-specific energy demands is unknown. Here we compared mitochondrial morphology, protein expression, and calcium levels across CA1 and CA2 circuits. We found mitochondria in CA2 dendrites were larger than mitochondria in CA1 dendrites. However, both subregions harbored larger mitochondria in the entorhinal cortex (EC)-contacting distal dendrites compared to CA3-contacting proximal dendrites. Together, these data demonstrate both cell type- and input-specific regulation of mitochondrial morphology that likely influences the function of these distinct circuits. To determine whether differences in mitochondrial fission or fusion account for cell and/or layer specific differences in morphology, we immunostained for OPA1 and MFF, which showed a general enrichment in distal dendrites relative to proximal dendrites, and an unexpected increase in CA1 distal dendrites compared to CA2 distal dendrites. To show whether these morphological differences result in functionally distinct mitochondria, we measured mitochondrial calcium levels in live slices. We found a striking enrichment of mitochondrial calcium levels in CA2 distal dendrites relative to proximal dendrites, and this layer-specific effect was significantly different from that in CA1 dendrites at baseline and after activity. Collectively, these findings reveal discrete morphological and functional differences in mitochondria across hippocampal subregions and dendritic layers, which likely confer unique circuit properties and/or vulnerabilities to disease.

Hippocampal area CA2 is unique in many ways, largely based on the complement of genes expressed there. We and others have observed that CA2 neurons exhibit a uniquely robust tropism for adeno-associated viruses (AAVs) of multiple serotypes and variants. In this study, we aimed to systematically investigate the propensity for AAV tropism toward CA2 across a wide range of AAV serotypes and variants, injected either intrahippocampally or systemically, including AAV1, 2, 5, 6, 8, 9, DJ, PHP.B, PHP.eB, and CAP-B10. We found that most serotypes and variants produced disproportionally high expression of AAV-delivered genetic material in hippocampal area CA2, although two serotypes (AAV6 and DJ) did not. In an effort to understand the mechanism(s) behind this observation, we considered perineuronal nets (PNNs) that ensheathe CA2 pyramidal cells and, among other functions, buffer diffusion of ions and molecules. We hypothesized that PNNs might attract AAV particles and maintain them in close proximity to CA2 neurons, thereby increasing exposure to AAV particles. However, genetic deletion of PNNs from CA2 had no effect on AAV transduction. Next, we next considered the AAV binding factors and receptors known to contribute to AAV transduction. We found that the AAV receptor (AAVR), which is critical to transduction, is abundantly expressed in CA2, and knockout of AAVR nearly abolished expression of AAV-delivered material by all serotypes tested. Additionally, we found CA2 enrichment of several cell-surface glycan receptors that AAV particles attach to before interacting with AAVR, including heparan sulfate proteoglycans, N-linked sialic acid and N-linked galactose. Indeed, CA2 showed the highest expression of AAVR and the investigated glycan receptors within the hippocampus. We conclude that CA2 neurons are endowed with multiple factors that make it highly susceptible to AAV transduction, particularly to the systemically available PHP variants, including CAP-B10. Given the curved structure of hippocampus and the relatively small size of CA2, systemic delivery of engineered PHP or CAP variants could all but eliminate the need for intrahippocampal AAV injections, particularly when injecting recombinase-dependent AAVs into animals that express recombinases in CA2.

Study of the hippocampal place cell system has greatly enhanced our understanding of memory encoding for distinct places, but how episodic memories for distinct experiences occurring within familiar environments are encoded is not clear. One possibility is that different place cell populations encode details of the novel experience or maintain the representation of the unchanged environment. We developed an aversive spatial decision making task which induced partial remapping in CA1, allowing us to identify both remapping and stable cell populations. We found that remapping cells exhibited distinct features not present in stable cells. During memory encoding, their theta phase preferences shifted to earlier phases, when CA3 inputs are strongest. Further, their recruitment into replay events increased during learning, unlike that of stable cells. Our demonstration of a sub-population of place cells identified on the basis of their degree of remapping and exhibiting unique changes in their spike firing properties with learning lend support to a model in which novel and familiar spatial/contextual information is encoded and maintained, respectively, by separate place cell populations.

Theta and gamma rhythms temporally coordinate sequences of hippocampal place cell ensembles during active behaviors, while sharp wave-ripples coordinate place cell sequences during rest. We used a delayed match-to-place memory task to investigate whether such coordination of hippocampal place cell sequences is disrupted when memory errors occur. As rats approached a learned reward location, place cell sequences represented paths extending toward the reward location during correct trials. During error trials, paths coded by place cell sequences were significantly shorter as rats approached incorrect stop locations, with place cell sequences starting at a significantly delayed phase of the theta cycle. During rest, place cell sequences replayed representations of paths that were highly likely to end at the correct reward location during correct but not error trials. The relationship between place cell sequences and gamma rhythms, however, did not differ between correct and error trials. These results suggest that coordination of place cell sequences by theta rhythms and sharp wave-ripples is important for successful spatial memory.

Hippocampal theta oscillations regulate the timing of neurons to support navigation, memory formation, and sensorimotor integration. Theta is modulated by running speed, breathing, whisking, and jumping and increases in tasks involving memory encoding or retrieval. The positive relationship between theta frequency and running speed is believed stabilize hippocampal representations of space amid movement variability. Here, we incorporated a novel string-pulling task to determine if established relationships between movement and theta hold when progress to a reward is determined by the length of string pulled. This task eliminates many speed-associated inputs, such vestibular, visual, and hindlimb information, and allows an unprecedented level of precision in the analysis of individual paw movements. Given that animals move the string a fixed length to acquire a reward, we predicted that the positive relationship between theta frequency and speed would hold. ApproachFive Sprague Dawley rats (4 mo.) were trained to continuously pull a string a fixed distance of 208 cm using an automated string-pulling system and run on a track for food reward. Local-field data was acquired from electrodes in dorsal CA1. ResultsRelationships between theta and movement speed were distinct during string pulling and running. While theta was robust in both conditions, frequency was significantly reduced during string-pulling and showed no speed-frequency coupling, unlike running. This difference could result from the conflict between hindlimb and forelimb signals, with only forelimb movement signaling advancement. Fine-grained analysis of paw movements during string-pulling (lift, advance, grasp, pull, push) revealed that theta power and frequency peaked during the contralateral paws downward push despite paw speed being low during this action. This suggests that theta frequency and power could respond to effort rather than purely kinematic information. Notably, running-associated theta may similarly reflect both speed and effort as most locomotor tasks conflate these variables. Finally, theta phase aligned from one reach-pull cycle to the next during the downward pull motion - the first action that directly advances the string forward. Since phase-locking has been associated with sensorimotor gating, synchrony at this point could reflect the gating of inputs that are the most causally relevant for reaching the reward, potentially facilitating integration of action-outcome signals for memory encoding and navigation. Taken together, these data support a dual-scale view of hippocampal processing and theta-band activity where macroscale theta activity requires suprathreshold sensory, vestibular, and proprioceptive drive and microscale theta remains sensitive to subsecond limb movements.

Spatial memory in the hippocampus involves dynamic neural patterns that change over days, termed representational drift. While drift may aid memory updating, excessive drift could impede retrieval. Memory retrieval is influenced by reward expectation during encoding, so we hypothesized that diminished reward expectation would exacerbate representational drift. We found that high reward expectation limited drift, with CA1 representations on one day gradually re-emerging over successive trials the following day. Conversely, the absence of reward expectation resulted in increased drift, as the gradual re-emergence of the previous days representation did not occur. At the single cell level, lowering reward expectation caused an immediate increase in the proportion of place-fields with low trial-to-trial reliability. These place fields were less likely to be reinstated the following day, underlying increased drift in this condition. In conclusion, heightened reward expectation improves memory encoding and retrieval by maintaining reliable place fields that are gradually reinstated across days, thereby minimizing representational drift.

Navigation requires integrating sensory information with a stable schema to create a dynamic map of an animals position using egocentric and allocentric coordinate systems. In the hippocampus, place cells encode allocentric space, but their firing rates may also exhibit directional tuning within egocentric or allocentric reference frames. We compared experimental and simulated data to assess the prevalence of tuning to egocentric bearing (EB) among hippocampal cells in rats foraging in an open field. Using established procedures, we confirmed egocentric modulation of place cell activity in recorded data; however, simulated data revealed a high false positive rate. When we accounted for false positives by comparing with shuffled data that retain correlations between the animals direction and position, only a very low number of hippocampal neurons appeared modulated by EB. Our study highlights biases affecting false positive rates and provides insights into the challenges of identifying egocentric modulation in hippocampal neurons.

Recent work in cognitive and systems neuroscience has suggested that the hippocampus might support planning, imagination, and navigation by forming "cognitive maps" that capture the structure of physical spaces, tasks, and situations. Critically, navigation involves planning within a context and disambiguating similar contexts to reach a goal. We examined hippocampal activity patterns in humans during a goal-directed navigation task to examine how contextual and goal information are incorporated in the construction and execution of navigational plans. Results demonstrate that, during planning, the hippocampus carries a context-specific representation of a future goal. Importantly, this effect could not be explained by stimulus or spatial information alone. During navigation, we observed reinstatement of activity patterns in the hippocampus ahead of participants required actions, which was strongest for behaviorally relevant points in the sequence. These results suggest that, rather than simply representing overlapping associations, hippocampal activity patterns are powerfully shaped by context and goals.

The hippocampus is believed to be an important region for spatial navigation, helping to represent the environment and plan routes. Evidence from rodents has suggested that the hippocampus processes information in a graded manner along its long-axis, with anterior regions encoding coarse information and posterior regions encoding fine-grained information. Brunec et al. (2018) demonstrated similar patterns in humans in a navigation paradigm, showing that the anterior-posterior gradient in representational granularity and the rate of signal change exist in the human hippocampus. However, the stability of these signals and their relationship to navigational performance remain unclear. In this study, we conducted a two-week training program where participants learned to navigate through a novel city environment. We investigated inter-voxel similarity (IVS) and temporal auto-correlation hippocampal signals, measures of representational granularity and signal change, respectively. Specifically, we investigated how these signals were influenced by navigational ability (i.e., stronger vs. weaker spatial learners), training session, and navigational dynamics. Our results revealed that stronger learners exhibited a clear anterior-posterior distinction in IVS in the right hippocampus, while weaker learners showed less pronounced distinctions. Additionally, lower general IVS levels in the hippocampus were linked to better early learning. Successful navigation was characterized by faster signal change, particularly in the anterior hippocampus, whereas failed navigation lacked the anterior-posterior distinction in signal change. These findings suggest that signal complexity and signal change in the hippocampus are important factors for successful navigation, with IVS representing information organization and auto-correlation reflecting moment-to-moment updating. These findings support the idea that efficient organization of scales of representation in an environment may be necessary for efficient navigation itself. Understanding the dynamics of these neural signals provides insights into the mechanisms underlying navigational learning in humans.