Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat
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eLife Assessment
This important study investigates how the hippocampus distinguishes between reactive escape and anticipatory withdrawal during approach-avoidance conflict in rats performing a naturalistic decision-making task. Solid evidence supports the main finding that hippocampal neuronal representations differ during different types of defensive behaviors. The study will be of interest to researchers studying memory, navigation, and decision-making in the presence of competing rewards and threats.
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Abstract
Adaptive behavior under threat requires balancing reward pursuit against the risk of harm. During approach-avoidance conflict, animals often pause at decision points, but whether these pauses reflect a unified process or distinct decision states remains unclear. Here, we replicate and extend findings from Calvin et al.1 by analyzing hippocampal activity in rats performing a pseudo-predator foraging task across two cohorts. We compared mid-track aborts (MTAs), mid-track continues (MTCs), and retreats. Behaviorally, MTAs and MTCs emerged from a shared pause state but diverged in outcome, whereas retreats reflected rapid escape following attack. Despite similar endpoints, retreats and MTAs differed in movement dynamics and neural activity. During retreats, hippocampal representations remained biased toward the attack location. In contrast, representations during MTAs shifted toward safe locations. During pauses, representations differed according to subsequent behavior: pauses preceding MTAs showed greater decoded probability near the attack region, whereas pauses preceding MTCs showed greater decoded probability to goal locations. These differences were present during the outbound approach, suggesting decision-related processes emerged early on in the journey. Together, these findings dissociate hippocampal representations associated with reactive escape from those underlying anticipatory, anxiety-like decision-making, suggesting that the hippocampus dynamically tracks behaviorally relevant features to guide decisions under threat.
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eLife Assessment
This important study investigates how the hippocampus distinguishes between reactive escape and anticipatory withdrawal during approach-avoidance conflict in rats performing a naturalistic decision-making task. Solid evidence supports the main finding that hippocampal neuronal representations differ during different types of defensive behaviors. The study will be of interest to researchers studying memory, navigation, and decision-making in the presence of competing rewards and threats.
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Reviewer #1 (Public review):
Damphousse, Calvin and Redish recorded from dorsal hippocampus in rats running past a robotic predator to reach food. They re-analyzed the cohort from Calvin et al. (2025, PLoS Biol) and added a new cohort. They compared three behaviors: retreats right after an attack, mid-track aborts (MTAs) where the rat turns back without being attacked, and mid-track continues (MTCs) where the rat pauses and then carries on. The authors report that retreats and MTAs, though both end at the nest, differed in speed and in decoded position. During retreats, decoding stayed near the attack zone. During MTAs, it was weighted more toward the nest and the far end of the track. Pauses that ended in an abort showed more decoding of the attack zone than pauses that ended in continuing, and a similar difference was seen on the way …
Reviewer #1 (Public review):
Damphousse, Calvin and Redish recorded from dorsal hippocampus in rats running past a robotic predator to reach food. They re-analyzed the cohort from Calvin et al. (2025, PLoS Biol) and added a new cohort. They compared three behaviors: retreats right after an attack, mid-track aborts (MTAs) where the rat turns back without being attacked, and mid-track continues (MTCs) where the rat pauses and then carries on. The authors report that retreats and MTAs, though both end at the nest, differed in speed and in decoded position. During retreats, decoding stayed near the attack zone. During MTAs, it was weighted more toward the nest and the far end of the track. Pauses that ended in an abort showed more decoding of the attack zone than pauses that ended in continuing, and a similar difference was seen on the way out, before the pause.
The main contribution is conceptual. Separating fear-like escape from anxiety-like withdrawal within the same task is a real step beyond showing that the hippocampus represents threat. The task places the robot, the attack threshold and the reward at different points on the track, which makes the decoding easier to interpret. Figs. 5-7 use the same analysis layout, so the comparisons are easy to follow. The main patterns are seen in both cohorts, even though the cohorts differ in several procedural details.
The revision tightens the abstract, clarifies how epochs were defined and normalized, and acknowledges that the results are correlational. Overall, the data support the main conclusion that hippocampal representations differ between reactive and anticipatory responses to threat. The paper should interest people working on hippocampus, defensive behavior and approach-avoidance conflict, and the task offers a good way to study how threat and reward are weighed against each other.
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Reviewer #2 (Public review):
Summary:
This manuscript extends previous work from Calvin et al. and examines hippocampal representations during approach-avoidance conflict in a robotic predator foraging task. The paradigm itself is very interesting and addresses an important but relatively understudied question in the navigation and foraging literature: how the brain balances risk versus reward during goal-directed behavior. While hippocampal representations of positively valenced goals and future intentions have been extensively studied, much less is known about how these representations evolve during risk-reward tradeoffs involving threat.
The authors use a relatively simple and interpretable decoding approach together with thoughtful behavioral comparisons to ask whether future behavioral outcome can be read out from hippocampal …
Reviewer #2 (Public review):
Summary:
This manuscript extends previous work from Calvin et al. and examines hippocampal representations during approach-avoidance conflict in a robotic predator foraging task. The paradigm itself is very interesting and addresses an important but relatively understudied question in the navigation and foraging literature: how the brain balances risk versus reward during goal-directed behavior. While hippocampal representations of positively valenced goals and future intentions have been extensively studied, much less is known about how these representations evolve during risk-reward tradeoffs involving threat.
The authors use a relatively simple and interpretable decoding approach together with thoughtful behavioral comparisons to ask whether future behavioral outcome can be read out from hippocampal activity before behavior diverges. The most compelling comparison is between mid-track aborts (MTAs) and mid-track continues (MTCs), where the animals initially exhibit very similar pause behavior but ultimately either abort or continue the trajectory. The authors show that decoded location during these pauses differs prior to the overt manifestation of the behavioral decision, suggesting that hippocampal representations may reflect evolving internal evaluation processes during approach-avoidance conflict.
Strengths:
A major strength of the work is the behavioral paradigm itself. This type of risk-reward conflict task is relatively uncommon in the hippocampal navigation literature and provides a rich framework for examining defensive decision-making during naturalistic foraging behavior.
The decoding analyses are also relatively simple and easy to interpret. Rather than relying on highly complex modeling approaches, the authors use straightforward comparisons of decoded spatial representations across behavioral conditions, making the results accessible and conceptually clear.
Another strength is the use of behavioral controls to isolate comparisons between related behaviors. In particular, the comparison between MTAs and MTCs is compelling because the animals exhibit similar pause states before the behavioral outcomes diverge. This provides a useful framework for asking whether hippocampal activity reflects future behavioral outcome before the decision is overtly expressed.
Overall, the study asks an interesting question using a novel paradigm and provides evidence that hippocampal representations during approach-avoidance conflict may reflect future behavioral trajectory.
Weaknesses:
The main weakness is that many of the reported effects are relatively subtle and are not sufficiently controlled for differences in speed, trajectory structure, and other behavioral variables across conditions. While the subtraction plots (green versus purple decoding differences) appear visually striking, the actual effect sizes are fairly small, making it difficult to assess how robust or behaviorally meaningful these differences are.
Relatedly, many of the most interesting questions in this task concern how behavior unfolds dynamically within a trial, yet much of the analysis averages across events and trajectories. As a result, potentially important aspects of the behavior may be obscured.
In particular, the manuscript would benefit from richer characterization of the animals' actual movement trajectories and spatial strategies. Because the analyses rely heavily on linearized position, it is difficult to determine whether animals behave differently in two-dimensional space across conditions. For example, during continued approaches, do animals preferentially hug the wall opposite the robot? Do different behavioral conditions show distinct lateral occupancy or trajectory structure? These types of analyses would make the behavioral interpretation substantially more compelling.
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Reviewer #3 (Public review):
Summary:
The study reanalyzes data from a previously published cohort together with an additional cohort to investigate hippocampal activity during approach-avoidance conflict. Unlike many prior studies that isolate reward- or threat-based learning, this task requires animals to evaluate reward and threat concurrently. The central finding is that hippocampal representations differ between hesitant behaviors that lead to approach versus avoidance outcomes, with representations of the attack zone more likely during pauses preceding abort decisions. This is an important extension of prior work on hippocampal activity and deliberation, suggesting that the hippocampal content may help shape the eventual outcome.
Strengths:
All behavioral findings are replicated independently across cohorts, making the behavioral …
Reviewer #3 (Public review):
Summary:
The study reanalyzes data from a previously published cohort together with an additional cohort to investigate hippocampal activity during approach-avoidance conflict. Unlike many prior studies that isolate reward- or threat-based learning, this task requires animals to evaluate reward and threat concurrently. The central finding is that hippocampal representations differ between hesitant behaviors that lead to approach versus avoidance outcomes, with representations of the attack zone more likely during pauses preceding abort decisions. This is an important extension of prior work on hippocampal activity and deliberation, suggesting that the hippocampal content may help shape the eventual outcome.
Strengths:
All behavioral findings are replicated independently across cohorts, making the behavioral results highly convincing. The design is robust, and the task is especially valuable for studying approach-avoidance conflict. The behavioral paradigm is complex and rare, and neuronal recordings in such a paradigm are of great value.
The major strength of the study is the comparison of neural activity during hesitant behavior leading to different outcomes; namely, pauses followed by the animal aborting the approach (mid-track aborts), and pauses followed by the animal committing to the approach (mid-track continues). Hippocampal activity differed between the two pauses: the attack zone was more likely to be represented during mid-track aborts. The same effect was observed on the journey before the pause: even before the animal hesitates, hippocampal activity before a pause that led to a mid-track abort was more likely to represent the attack zone than hippocampal activity before pauses that led to continued approach. This analysis suggests that hippocampal content before and during deliberative behavior is predictive of the animal's decision.
Weaknesses:
The interpretation of the retreat-related decoding results is less clear. The study compares two sets of retreating behavior: on the one hand, retreat after being attacked, and on the other hand, retreat after hesitation in the absence of an attack (a mid-track abort). Hippocampal activity represents the attack zone more after the animal is attacked. However, these two retreating behaviors originate from different spatial locations: retreats always start past the "attack threshold", while mid-track aborts always start before this threshold. Given that hippocampal decoding is strongly location-dependent, this difference in position makes the neural decoding results difficult to interpret. The increased representation may be due to differences in physical location, rather than distinct processing of immediate threat and an anticipatory return state.
Comments on revised version.
The revised manuscript is indeed more clear, but the study is largely unchanged.
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Author response:
The following is the authors’ response to the original reviews.
Public Reviews:
Reviewer #1 (Public review):
Summary:
This study by Damphousse, Calvin, and Redish investigates how the hippocampus represents competing future outcomes during approach-avoidance conflict. Using an ethologically relevant robotic predator foraging paradigm, the authors aimed to dissociate hippocampal activity associated with reactive defensive responses (escape) from that linked to anticipatory withdrawal decisions. The central finding is that dorsal hippocampal representations differentiate these two modes of defensive behavior within a single naturalistic assay. Specifically, the authors show that attack-triggered retreats and mid-track aborts differ in movement dynamics and hippocampal spatial decoding despite sharing a common …
Author response:
The following is the authors’ response to the original reviews.
Public Reviews:
Reviewer #1 (Public review):
Summary:
This study by Damphousse, Calvin, and Redish investigates how the hippocampus represents competing future outcomes during approach-avoidance conflict. Using an ethologically relevant robotic predator foraging paradigm, the authors aimed to dissociate hippocampal activity associated with reactive defensive responses (escape) from that linked to anticipatory withdrawal decisions. The central finding is that dorsal hippocampal representations differentiate these two modes of defensive behavior within a single naturalistic assay. Specifically, the authors show that attack-triggered retreats and mid-track aborts differ in movement dynamics and hippocampal spatial decoding despite sharing a common behavioral endpoint, that hippocampal representations during pauses predict subsequent behavioral outcomes, and that these representational biases emerge before overt behavioral divergence. The main importance of the study lies in moving beyond viewing the hippocampus as merely encoding spatial location or threat salience, instead suggesting that hippocampal ensemble activity dynamically tracks and differentially weights threat-related, reward-related, and safety-oriented future states to bias behavior before overt action occurs.
Strengths:
The study has several notable strengths. First, the behavioral decomposition into retreats, mid-track aborts, and mid-track continues is rigorous and provides a highly interpretable analytical framework. Second, replication across two independent cohorts - despite differences in arena configuration, robot design, and extinction procedures - meaningfully strengthens confidence in the robustness of the findings. Third, the unified reanalysis pipeline across cohorts reflects strong analytical discipline, and the Bayesian decoding framework is well-suited to addressing the central representational questions. Fourth, the ethological relevance of the robotic predator paradigm is a major advantage, allowing the authors to examine a richer repertoire of defensive and decision-related behaviors than is possible in conventional fear-conditioning assays. Overall, the experiments are well designed, the data are clearly presented, and the findings make a valuable contribution to understanding how the hippocampus supports decision-making under threat.
Weaknesses:
The study is technically strong, but a few modest revisions would further enhance it.
(1) First, the abstract mentions extinction and reinstatement effects, but neural analyses focus primarily on the attack phase. It would be helpful to clarify or adjust the abstract accordingly.
(2) Second, some interpretive language ("guide," "bias") leans toward causal phrasing. Given the correlational data, using "predict" or "correlate with" would be more precise.
(3) Third, given the relationship between running speed and hippocampal theta, considering speed-related contributions to decoding differences would be useful.
(4) Fourth, reporting turnaround positions for mid-track abort and continue trials (Figure 7) would provide helpful context.
(5) Fifth, a figure comparing stimulated vs. non-stimulated sessions in cohort 2 would support the claim that closed-loop stimulation had no measurable effect.
(6) Finally, reporting effect sizes for key decoding comparisons would add clarity.
Reviewer #2 (Public review):
Summary:
This manuscript extends previous work from Calvin et al. and examines hippocampal representations during approach-avoidance conflict in a robotic predator foraging task. The paradigm itself is very interesting and addresses an important but relatively understudied question in the navigation and foraging literature: how the brain balances risk versus reward during goal-directed behavior. While hippocampal representations of positively valenced goals and future intentions have been extensively studied, much less is known about how these representations evolve during risk-reward tradeoffs involving threat.
The authors use a relatively simple and interpretable decoding approach together with thoughtful behavioral comparisons to ask whether future behavioral outcomes can be read out from hippocampal activity before behavior diverges. The most compelling comparison is between mid-track aborts (MTAs) and mid-track continues (MTCs), where the animals initially exhibit very similar pause behavior but ultimately either abort or continue the trajectory. The authors show that decoded location during these pauses differs prior to the overt manifestation of the behavioral decision, suggesting that hippocampal representations may reflect evolving internal evaluation processes during approach-avoidance conflict.
Strengths:
A major strength of the work is the behavioral paradigm itself. This type of risk-reward conflict task is relatively uncommon in the hippocampal navigation literature and provides a rich framework for examining defensive decision-making during naturalistic foraging behavior.
The decoding analyses are also relatively simple and easy to interpret. Rather than relying on highly complex modeling approaches, the authors use straightforward comparisons of decoded spatial representations across behavioral conditions, making the results accessible and conceptually clear.
Another strength is the use of behavioral controls to isolate comparisons between related behaviors. In particular, the comparison between MTAs and MTCs is compelling because the animals exhibit similar pause states before the behavioral outcomes diverge. This provides a useful framework for asking whether hippocampal activity reflects future behavioral outcome before the decision is overtly expressed.
Overall, the study asks an interesting question using a novel paradigm and provides evidence that hippocampal representations during approach-avoidance conflict may reflect future behavioral trajectory.
Weaknesses:
The main weakness is that many of the reported effects are relatively subtle and are not sufficiently controlled for differences in speed, trajectory structure, and other behavioral variables across conditions. While the subtraction plots (green versus purple decoding differences) appear visually striking, the actual effect sizes are fairly small, making it difficult to assess how robust or behaviorally meaningful these differences are.
Relatedly, many of the most interesting questions in this task concern how behavior unfolds dynamically within a trial, yet much of the analysis averages across events and trajectories. As a result, potentially important aspects of the behavior may be obscured.
In particular, the manuscript would benefit from richer characterization of the animals' actual movement trajectories and spatial strategies. Because the analyses rely heavily on linearized position, it is difficult to determine whether animals behave differently in two-dimensional space across conditions. For example, during continued approaches, do animals preferentially hug the wall opposite the robot? Do different behavioral conditions show distinct lateral occupancy or trajectory structure? These types of analyses would make the behavioral interpretation substantially more compelling.
More generally, while the results are suggestive and interesting, the relatively small decoding differences and substantial behavioral confounds make it difficult to conclude that the observed effects reflect distinct internal evaluative or threat-related states.
Reviewer #3 (Public review):
Summary:
The study reanalyzes data from a previously published cohort together with an additional cohort to investigate hippocampal activity during approach-avoidance conflict. Unlike many prior studies that isolate reward- or threat-based learning, this task requires animals to evaluate reward and threat concurrently. The central finding is that hippocampal representations differ between hesitant behaviors that lead to approach versus avoidance outcomes, with representations of the attack zone more likely during pauses preceding abort decisions. This is an important extension of prior work on hippocampal activity and deliberation, suggesting that the hippocampal content may help shape the eventual outcome.
Strengths:
All behavioral findings are replicated independently across cohorts, making the behavioral results highly convincing. The design is robust, and the task is especially valuable for studying approach-avoidance conflict. The behavioral paradigm is complex and rare, and neuronal recordings in such a paradigm are of great value.
The major strength of the study is the comparison of neural activity during hesitant behavior leading to different outcomes, namely, pauses followed by the animal aborting the approach (mid-track aborts), and pauses followed by the animal committing to the approach (mid-track continues). Hippocampal activity differed between the two pauses: the attack zone was more likely to be represented during mid-track aborts. The same effect was observed on the journey before the pause: even before the animal hesitates, hippocampal activity before a pause that led to a mid-track abort was more likely to represent the attack zone than hippocampal activity before pauses that led to continued approach. This analysis suggests that hippocampal content before and during deliberative behavior is predictive of the animal's decision.
Weaknesses:
The interpretation of the retreat-related decoding results is less clear. The study compares two sets of retreating behavior: on the one hand, retreat after being attacked, and on the other hand, retreat after hesitation in the absence of an attack (a mid-track abort). Hippocampal activity represents the attack zone more after the animal is attacked. However, these two retreating behaviors originate from different spatial locations: retreats always start past the "attack threshold", while mid-track aborts always start before this threshold. Given that hippocampal decoding is strongly location-dependent, this difference in position makes the neural decoding results difficult to interpret. The increased representation may be due to differences in physical location, rather than the distinct processing of immediate threat and an anticipatory return state.
We thank the reviewers for their careful, constructive, and fair assessment of our manuscript, “Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat.” We were pleased that the assessment characterized our study as important and the evidence supporting its main finding as solid. We also appreciate the reviewers’ recognition of the strengths of the behavioral paradigm and the conceptual contribution of distinguishing hippocampal representations associated with reactive and anticipatory responses to threat.
We carefully considered the reviewers’ comments and do not feel that the manuscript requires extensive revision. The reviewers suggested several thoughtful additional analyses, including further behavioral controls and explicit predictive analyses. We agree that these would be informative and intend to carry several of these directions forward with future datasets. However, for the present manuscript, the suggested analyses would extend the scope of the work but are unlikely to substantially alter the central observations, and we have therefore chosen not to undertake them for the present manuscript.
We have only made very minor changes to the text and figures, corresponding to what we might do in a manuscript that had been “accepted” under the old-style journal process. We have
- Revised the abstract to more accurately reflect the neural analyses presented.
- Softened the interpretive language throughout to avoid implying causality where the data establish associations, and explicitly acknowledged this limitation in the discussion.
- Clarified the explanation of the timing and location of robot attacks relative to the attack threshold.
- Clarified the definitions and explanations of the temporal segmentation of MTA and MTC pauses.
- Clarified the explanations of the outbound epoch used in the MTA-MTC comparison.
- Expanded the methods describing temporal and spatial normalization of behavioral epochs.
- Moved the headers on figures 5-7 as suggested by the reviewers to make them more clear.
With these revisions, we believe the manuscript now accurately reflects what can be concluded from the current data and appropriately acknowledges the limitations raised during review.
We sincerely thank the editor and reviewers for their thoughtful engagement. Their comments have improved the clarity and precision of the manuscript and provided valuable directions for future work.
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Authors published a paper in Biorxiv, they used KiloSort in the study. Including #RRIDs will make this less ambiguous. SciScore made a table with this resource, see “Automated Services” module (download as csv, xml or #jats) #reproducibility #STMpublishing
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Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat elifesciences.org/reviewed-pre...
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eLife Assessment
This important study investigates how the hippocampus distinguishes between reactive escape and anticipatory withdrawal during approach-avoidance conflict in rats performing a naturalistic decision-making task. Solid evidence supports the main finding that hippocampal neuronal representations differ during different types of defensive behaviors, although the evidence for some of the claims in the paper could be strengthened. The study will be of interest to researchers studying memory, navigation, and decision-making in the presence of competing rewards and threats.
-
Reviewer #1 (Public review):
Summary:
This study by Damphousse, Calvin, and Redish investigates how the hippocampus represents competing future outcomes during approach-avoidance conflict. Using an ethologically relevant robotic predator foraging paradigm, the authors aimed to dissociate hippocampal activity associated with reactive defensive responses (escape) from that linked to anticipatory withdrawal decisions. The central finding is that dorsal hippocampal representations differentiate these two modes of defensive behavior within a single naturalistic assay. Specifically, the authors show that attack-triggered retreats and mid-track aborts differ in movement dynamics and hippocampal spatial decoding despite sharing a common behavioral endpoint, that hippocampal representations during pauses predict subsequent behavioral outcomes, …
Reviewer #1 (Public review):
Summary:
This study by Damphousse, Calvin, and Redish investigates how the hippocampus represents competing future outcomes during approach-avoidance conflict. Using an ethologically relevant robotic predator foraging paradigm, the authors aimed to dissociate hippocampal activity associated with reactive defensive responses (escape) from that linked to anticipatory withdrawal decisions. The central finding is that dorsal hippocampal representations differentiate these two modes of defensive behavior within a single naturalistic assay. Specifically, the authors show that attack-triggered retreats and mid-track aborts differ in movement dynamics and hippocampal spatial decoding despite sharing a common behavioral endpoint, that hippocampal representations during pauses predict subsequent behavioral outcomes, and that these representational biases emerge before overt behavioral divergence. The main importance of the study lies in moving beyond viewing the hippocampus as merely encoding spatial location or threat salience, instead suggesting that hippocampal ensemble activity dynamically tracks and differentially weights threat-related, reward-related, and safety-oriented future states to bias behavior before overt action occurs.
Strengths:
The study has several notable strengths. First, the behavioral decomposition into retreats, mid-track aborts, and mid-track continues is rigorous and provides a highly interpretable analytical framework. Second, replication across two independent cohorts - despite differences in arena configuration, robot design, and extinction procedures - meaningfully strengthens confidence in the robustness of the findings. Third, the unified reanalysis pipeline across cohorts reflects strong analytical discipline, and the Bayesian decoding framework is well-suited to addressing the central representational questions. Fourth, the ethological relevance of the robotic predator paradigm is a major advantage, allowing the authors to examine a richer repertoire of defensive and decision-related behaviors than is possible in conventional fear-conditioning assays. Overall, the experiments are well designed, the data are clearly presented, and the findings make a valuable contribution to understanding how the hippocampus supports decision-making under threat.
Weaknesses:
The study is technically strong, but a few modest revisions would further enhance it.
(1) First, the abstract mentions extinction and reinstatement effects, but neural analyses focus primarily on the attack phase. It would be helpful to clarify or adjust the abstract accordingly.
(2) Second, some interpretive language ("guide," "bias") leans toward causal phrasing. Given the correlational data, using "predict" or "correlate with" would be more precise.
(3) Third, given the relationship between running speed and hippocampal theta, considering speed-related contributions to decoding differences would be useful.
(4) Fourth, reporting turnaround positions for mid-track abort and continue trials (Figure 7) would provide helpful context.
(5) Fifth, a figure comparing stimulated vs. non-stimulated sessions in cohort 2 would support the claim that closed-loop stimulation had no measurable effect.
(6) Finally, reporting effect sizes for key decoding comparisons would add clarity.
-
Reviewer #2 (Public review):
Summary:
This manuscript extends previous work from Calvin et al. and examines hippocampal representations during approach-avoidance conflict in a robotic predator foraging task. The paradigm itself is very interesting and addresses an important but relatively understudied question in the navigation and foraging literature: how the brain balances risk versus reward during goal-directed behavior. While hippocampal representations of positively valenced goals and future intentions have been extensively studied, much less is known about how these representations evolve during risk-reward tradeoffs involving threat.
The authors use a relatively simple and interpretable decoding approach together with thoughtful behavioral comparisons to ask whether future behavioral outcomes can be read out from hippocampal …
Reviewer #2 (Public review):
Summary:
This manuscript extends previous work from Calvin et al. and examines hippocampal representations during approach-avoidance conflict in a robotic predator foraging task. The paradigm itself is very interesting and addresses an important but relatively understudied question in the navigation and foraging literature: how the brain balances risk versus reward during goal-directed behavior. While hippocampal representations of positively valenced goals and future intentions have been extensively studied, much less is known about how these representations evolve during risk-reward tradeoffs involving threat.
The authors use a relatively simple and interpretable decoding approach together with thoughtful behavioral comparisons to ask whether future behavioral outcomes can be read out from hippocampal activity before behavior diverges. The most compelling comparison is between mid-track aborts (MTAs) and mid-track continues (MTCs), where the animals initially exhibit very similar pause behavior but ultimately either abort or continue the trajectory. The authors show that decoded location during these pauses differs prior to the overt manifestation of the behavioral decision, suggesting that hippocampal representations may reflect evolving internal evaluation processes during approach-avoidance conflict.
Strengths:
A major strength of the work is the behavioral paradigm itself. This type of risk-reward conflict task is relatively uncommon in the hippocampal navigation literature and provides a rich framework for examining defensive decision-making during naturalistic foraging behavior.
The decoding analyses are also relatively simple and easy to interpret. Rather than relying on highly complex modeling approaches, the authors use straightforward comparisons of decoded spatial representations across behavioral conditions, making the results accessible and conceptually clear.
Another strength is the use of behavioral controls to isolate comparisons between related behaviors. In particular, the comparison between MTAs and MTCs is compelling because the animals exhibit similar pause states before the behavioral outcomes diverge. This provides a useful framework for asking whether hippocampal activity reflects future behavioral outcome before the decision is overtly expressed.
Overall, the study asks an interesting question using a novel paradigm and provides evidence that hippocampal representations during approach-avoidance conflict may reflect future behavioral trajectory.
Weaknesses:
The main weakness is that many of the reported effects are relatively subtle and are not sufficiently controlled for differences in speed, trajectory structure, and other behavioral variables across conditions. While the subtraction plots (green versus purple decoding differences) appear visually striking, the actual effect sizes are fairly small, making it difficult to assess how robust or behaviorally meaningful these differences are.
Relatedly, many of the most interesting questions in this task concern how behavior unfolds dynamically within a trial, yet much of the analysis averages across events and trajectories. As a result, potentially important aspects of the behavior may be obscured.
In particular, the manuscript would benefit from richer characterization of the animals' actual movement trajectories and spatial strategies. Because the analyses rely heavily on linearized position, it is difficult to determine whether animals behave differently in two-dimensional space across conditions. For example, during continued approaches, do animals preferentially hug the wall opposite the robot? Do different behavioral conditions show distinct lateral occupancy or trajectory structure? These types of analyses would make the behavioral interpretation substantially more compelling.
More generally, while the results are suggestive and interesting, the relatively small decoding differences and substantial behavioral confounds make it difficult to conclude that the observed effects reflect distinct internal evaluative or threat-related states.
-
Reviewer #3 (Public review):
Summary:
The study reanalyzes data from a previously published cohort together with an additional cohort to investigate hippocampal activity during approach-avoidance conflict. Unlike many prior studies that isolate reward- or threat-based learning, this task requires animals to evaluate reward and threat concurrently. The central finding is that hippocampal representations differ between hesitant behaviors that lead to approach versus avoidance outcomes, with representations of the attack zone more likely during pauses preceding abort decisions. This is an important extension of prior work on hippocampal activity and deliberation, suggesting that the hippocampal content may help shape the eventual outcome.
Strengths:
All behavioral findings are replicated independently across cohorts, making the behavioral …
Reviewer #3 (Public review):
Summary:
The study reanalyzes data from a previously published cohort together with an additional cohort to investigate hippocampal activity during approach-avoidance conflict. Unlike many prior studies that isolate reward- or threat-based learning, this task requires animals to evaluate reward and threat concurrently. The central finding is that hippocampal representations differ between hesitant behaviors that lead to approach versus avoidance outcomes, with representations of the attack zone more likely during pauses preceding abort decisions. This is an important extension of prior work on hippocampal activity and deliberation, suggesting that the hippocampal content may help shape the eventual outcome.
Strengths:
All behavioral findings are replicated independently across cohorts, making the behavioral results highly convincing. The design is robust, and the task is especially valuable for studying approach-avoidance conflict. The behavioral paradigm is complex and rare, and neuronal recordings in such a paradigm are of great value.
The major strength of the study is the comparison of neural activity during hesitant behavior leading to different outcomes, namely, pauses followed by the animal aborting the approach (mid-track aborts), and pauses followed by the animal committing to the approach (mid-track continues). Hippocampal activity differed between the two pauses: the attack zone was more likely to be represented during mid-track aborts. The same effect was observed on the journey before the pause: even before the animal hesitates, hippocampal activity before a pause that led to a mid-track abort was more likely to represent the attack zone than hippocampal activity before pauses that led to continued approach. This analysis suggests that hippocampal content before and during deliberative behavior is predictive of the animal's decision.
Weaknesses:
The interpretation of the retreat-related decoding results is less clear. The study compares two sets of retreating behavior: on the one hand, retreat after being attacked, and on the other hand, retreat after hesitation in the absence of an attack (a mid-track abort). Hippocampal activity represents the attack zone more after the animal is attacked. However, these two retreating behaviors originate from different spatial locations: retreats always start past the "attack threshold", while mid-track aborts always start before this threshold. Given that hippocampal decoding is strongly location-dependent, this difference in position makes the neural decoding results difficult to interpret. The increased representation may be due to differences in physical location, rather than the distinct processing of immediate threat and an anticipatory return state.
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Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat https://www.biorxiv.org/content/10.64898/2026.04.17.719234v1
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Hippocampal representations differentiate reactive and anticipatory responses during foraging under threat https://www.biorxiv.org/content/10.64898/2026.04.17.719234v1
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