Hippocampus最新文献

{"title":"Encoding Patterned Spatial Behavior in the Subiculum.","authors":"Su-Min Lee, Inah Lee","doi":"10.1002/hipo.70102","DOIUrl":"https://doi.org/10.1002/hipo.70102","url":null,"abstract":"<p><p>The subiculum, a key component of the medial temporal lobe (MTL), has traditionally been viewed as a relay station for hippocampal output to cortical regions. However, its intricate afferent and efferent connections with diverse brain areas suggest a more independent role in memory and spatial navigation. This review argues that the subiculum encodes regularities in environmental structures (e.g., boundaries, corners, axes) and behavioral patterns imposed by task demands, integrating hippocampal information into schematic representations for goal-directed actions. In conditions where perceptual constraints are dominantly fostering predictable behaviors, subicular neurons exhibit invariant firing properties tied to environmental features, such as boundary vector and axis tuning. However, during task-guided behaviors, subicular firing is further shaped by task-relevant mnemonic constraints, as seen in theta-phase-specific fields that segment space into pre- and postchoice zones, encoding variables such as context and choice. Anatomical evidence, including convergent CA1 inputs and local recurrent connections within the subiculum, supports this function, with subicular outputs to regions like the medial prefrontal cortex facilitating rule-guided action generation. Ultimately, the subiculum transforms granular hippocampal codes into memory schemas, enabling efficient navigation and behavior in complex environments.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":"e70102"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13139697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro-Stimulation Timing Framed Around an Averaged Theta Period of Stimulation Determines Hippocampal Recruitment in Cued Fear Conditioning.","authors":"Paula Gonçalves Vieira Teixeira, Leonardo de Oliveira Guarnieri, Grace Schenatto Pereira, Márcio Flávio Dutra Moraes","doi":"10.1002/hipo.70097","DOIUrl":"10.1002/hipo.70097","url":null,"abstract":"<p><p>The importance of precise timing of neuronal activity, relative to ongoing slower oscillations, is reshaping the engram theory and our understanding of how memories are encoded and stored. The hippocampal theta-wave phase-encoding of neuronal firing predicts behavioral outcomes and cognitive performance in memory tasks. A single external stimulus or a sensory/cognitive cue may induce Phase-Resetting shift of theta waves, without changing their frequency or power. This phenomenon seems to be a core mechanism for temporal coordination, information encoding, and memory formation. We hypothesize that not only Phase-Resetting, but temporally coded neuromodulation packaged around an averaged theta cycle of 140 ms, plays a role in engram formation. Inter-pulse microstimulation patterns (MS) consisting of six stimuli within a 140 ms period were applied to the intermedial CA3 hippocampal area of C57/BL6 mice. Each MS-pattern consisted of a 10-bit word (each bit representing a 14-ms bin), indicating the phase at which MS was applied. The randomized (MSr) or fixed pattern (MSf) stimulus was applied during a 30 s presentation of a pure tone (CS) that terminated with a 2 s/0.4 mA footshock (US). Sham animals underwent surgery and cued fear conditioning, but no MS. Cued fear memory was tested by presenting the CS (without MS) in a different context. The group of mice that received the MSf during conditioning showed higher levels of freezing compared to the Sham group; the MSr group did not. We measured c-Fos/NeuN labeling as a proxy for neuronal activity 90 min after memory retrieval. As expected, since cued-fear memory is predominantly amygdala-dependent, all groups showed an increase in c-Fos expression in the amygdala. However, only the MSf group had higher hippocampal activation after retrieval, suggesting that fixed pattern stimulation framed around an averaged theta cycle led to neuronal integration into the memory trace. Our findings indicate that temporal organization plays a crucial role in how memories are stored and accessed.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":"e70097"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociable Mechanisms Underlie Differences Between Memory and Metamemory in Older Adults: The Differentiating Role of Anxiety and Depression Symptoms.","authors":"Jennifer L Crawford, Alex A Adornato, Johanna Matulonis, Xi Chen, Jacob M Hooker, Anne S Berry","doi":"10.1002/hipo.70100","DOIUrl":"10.1002/hipo.70100","url":null,"abstract":"<p><p>The ability to remember (i.e., memory ability) and to accurately discern memory function (i.e., metamemory) are both important facets of cognition. In the present study, we examined the shared and distinct sources of variance across memory ability and metamemory using psychometrically validated measures of memory ability, metamemory, and anxiety and depression symptoms in conjunction with multimodal imaging (i.e., structural MRI, tau PET) in a sample of cognitively normal older adults (N = 72). Replicating a growing body of work, we found that metamemory was more tightly linked to anxiety and depression symptoms relative to objective measures of memory ability. Our results also revealed that the hippocampus was a critical locus of both memory ability and metamemory-hippocampal volume was positively associated with memory ability, but not metamemory, whereas increased hippocampal tau pathology exacerbated the negative effect of anxiety and depression symptoms on metamemory. Importantly, we also found that after controlling for anxiety and depression symptoms and tau burden, there was a positive association between memory ability and metamemory. Our findings also demonstrated the importance of assessing different facets of metamemory; self-reported memory contentment and ability, but not strategy use, showed the strongest relationships with both anxiety and depression symptoms and hippocampal tau burden. Together, these results suggest that both shared and distinct mechanisms underlie memory ability and metamemory processes in older adults. Chiefly, this work highlights the potential of metamemory measures as sensitive tools to understand affective processes that occur in both healthy and pathological aging, independent of memory ability.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":"e70100"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dentate Gyrus Grows Throughout Life Despite Turnover of Developmentally-Born Neurons.","authors":"Tina Ciric, Shaina P Cahill, Tyler Lin, Si-Ah Choi, Jason S Snyder","doi":"10.1002/hipo.70099","DOIUrl":"10.1002/hipo.70099","url":null,"abstract":"<p><p>Adult-born hippocampal neurons are highly plastic but there remains uncertainty about the magnitude of neurogenesis and its long-term functional consequences. Theoretical predictions indicate that adult neurogenesis should lead to substantial growth of the dentate gyrus (DG) granule cell population. However, in practice, most studies find no changes in total cell number across adulthood. This discrepancy may partly be a sensitivity issue, where small sample sizes and the examination of older age windows (when neurogenesis is reduced) have prevented detection. However, neurogenic growth could also be masked by the turnover of developmentally-born DG neurons, which are known to die off in normal aging. To address the question of how neuronal birth and loss impacts DG population dynamics, here we quantified numbers of developmentally-born neurons, proliferating Ki67+ cells (as a proxy for adult-born neurons), and total DG neurons from 2-18 months of age in the rat. We estimate that over this timeframe 670,000 adult-born neurons are added (30% of the total population). Consistent with neurogenic growth, the total number of DG neurons increased across adulthood. However, net growth was only 385,000 cells, which is less than predicted by adult neurogenesis alone. Indeed, 20% of developmentally-born neurons were lost over the same interval, and so we propose that the difference is explained by neuronal turnover. Neuronal persistence and turnover may be relevant for theories of hippocampal long-term memory, as well as for understanding psychiatric conditions that are characterized by hippocampal plasticity and atrophy.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":"e70099"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subsets of Single Neurons Predict Ensemble Activity and Memory Choices","authors":"Aditya Srinivasan,&nbsp;Aditya Behal,&nbsp;Kevin Guise,&nbsp;Matthew L. Shapiro","doi":"10.1002/hipo.70093","DOIUrl":"10.1002/hipo.70093","url":null,"abstract":"<div>\u0000 \u0000 <p>Finding elements of a complex network which contribute most to the network's overall behavior is an open problem in various fields. This challenge is particularly difficult in neuroscience as it requires identifying which of a mammalian brain's many millions of neurons inform specific behavioral choices. Using methods inspired by compressed sensing, we identified subsets of CA1 neuronal ensembles recorded while only male rats performed spatial memory and cue-approach tasks in a plus maze. These subsets consisted of the units with firing rates which co-varied most closely with overall ensemble activity. Unit activity from these predictive subsets asymmetrically predicted the activity of other units in the ensemble. Excluding the predictive subset had no effect on ensemble decoding of the rat's current location but reduced decoding of past and future locations, suggesting that the predictive subset encodes nonlocal information. Predictive subsets likely represent a hierarchical and sparse coding scheme used by CA1, and further investigation of the properties of these sub-populations may lead to additional insights into the basic computational processes of the brain.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147672805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Plasticity in Replay: Stability Through Anti-Hebbian Rules","authors":"Lior Baron,&nbsp;Kamran Diba,&nbsp;Asohan Amarasingham","doi":"10.1002/hipo.70089","DOIUrl":"10.1002/hipo.70089","url":null,"abstract":"<p>Hippocampal replay is now considered to be a cornerstone of memory consolidation, yet the synaptic plasticity rules governing its dynamics remain elusive. Under the standard asymmetric Hebbian spike-timing dependent plasticity (STDP) model, the same spike patterns that promote activity propagation along one direction of sequential activation undermine propagation in the reverse direction, compromising “bidirectional” replay. On the other hand, symmetric potentiation rules, as recently proposed for region CA3, risk corrupting the memory trace by saturating synaptic weights. Using Ecker et al.'s recurrent network model of place cells that spontaneously generate replays during ripples, we systematically investigated how different STDP plasticity rules modulate offline replays. We developed a classification framework to study the mechanisms relating different STDP kernels to key replay characteristics, including directionality, speed, and stability. Our results confirmed that symmetric potentiation rules during offline states saturate synapses, inducing rigid attractors that corrupt the memory trace, and that an asymmetric Hebbian STDP kernel induces strong biases in the directionality of replay, leading to rapid replay acceleration and replay degradation. Notably, we found that an asymmetric anti-Hebbian STDP kernel preserves replay bi-directionality and stabilizes replay speed. We further identified the negative timing component of the STDP rule as the primary driver of replay speed: potentiation causes deceleration, while depression causes acceleration. These findings provide a mechanistic explanation for empirically observed replay deceleration and suggest a role for anti-Hebbian synaptic depression in stabilizing replay dynamics.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13069501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Attentional Deficits Do Not Explain Age-Related Impairments on the Mnemonic Similarity Task","authors":"Casey R. Vanderlip,&nbsp;Hasan Salim,&nbsp;Alexis Houle,&nbsp;Aryana Cortes,&nbsp;Anna Virovka,&nbsp;Yaxuan Liang,&nbsp;Katelyn Luc,&nbsp;Alexis Kellogg,&nbsp;Craig E. L. Stark","doi":"10.1002/hipo.70095","DOIUrl":"10.1002/hipo.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>The Mnemonic Similarity Task (MST) is increasingly used to assess mnemonic discrimination and has become a valuable tool for detecting subtle cognitive decline in aging and early Alzheimer's disease. Although designed to target hippocampal function, it is unlikely to be immune to attentional effects, leading to the possibility that age-related declines in the MST stem from attention rather than mnemonic impairments. Across three experiments, we found that attentional measures or modulations did not account for a substantial portion of age-related variance in mnemonic discrimination, underscoring that age-related deficits in the MST primarily reflect declines in memory and strengthening the MST's validity as a marker of hippocampal function.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress-Enhanced Fear Learning (SEFL) Is Associated With Enhanced Reactivation of Fear Engrams in Caudal But Not Rostral Dentate Gyrus","authors":"Denisse Paredes,&nbsp;Michael R. Drew","doi":"10.1002/hipo.70092","DOIUrl":"10.1002/hipo.70092","url":null,"abstract":"<p>Traumatic stress can cause long-lasting changes in cognition and affect, sometimes leading to diagnoses such as posttraumatic stress disorder (PTSD). The stress-enhanced fear learning (SEFL) model recapitulates understudied components of PTSD, such as trauma-induced sensitization of fear learning. The SEFL procedure entails exposing mice to footshock stress followed later by fear conditioning in a different context. When tested later for recall of fear conditioning, previously stressed mice exhibit enhanced freezing compared to non-stressed controls. Studies have shown that dorsal and ventral dentate gyrus (DG) generate neural ensemble representations of contextual fear, such that fear recall involves reactivation of a sparse set of “engram cells” that were active during fear memory acquisition. How stress affects these hippocampal ensemble representations is unknown. We used SEFL and activity-dependent neuronal tagging with FosTRAP2 mice to investigate effects of stress on fear memory ensembles in rostral and caudal hippocampal DG. FosTRAP2/Ai6 mice received footshock stress or equivalent context exposure without shock in Context A on day 1. Five days later, mice received 1-shock conditioning in Context B and immediately received an injection of 4-hydroxytamoxifen (4-OHT; 55 mg/kg) to tag fear acquisition neurons with the zsGreen reporter. One day later, mice were tested for fear recall in Context B and were perfused 90 min after testing. Confirming prior studies, stress potentiated 1-shock conditioning in Context B, with stressed mice displaying higher freezing in the Context B test session than nonstressed mice. At the level of neural activity, results showed stress had no effect on the number of zsGreen+ fear ensemble cells or the number of cfos+ recall-activated cells in rostral or caudal DG. However, stress increased reactivation (percentage of zsGreen+ cells expressing cfos) in the caudal but not rostral DG. The results suggest stress potentiates later fear learning by enhancing fear representations in caudal hippocampus, a region specialized for integrating emotional and motivational valence into memory.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13065500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover Image, Volume 36, Issue 2","authors":"Alix Guinet,&nbsp;Joachim Behr,&nbsp;Imre Vida,&nbsp;Sabine Grosser","doi":"10.1002/hipo.70096","DOIUrl":"10.1002/hipo.70096","url":null,"abstract":"<p>The cover image is based on the article <i>Spatial Organization of Morpho-Electric Subtypes of Pyramidal Neuron in the Subiculum</i> by Alix Guinet et al., https://doi.org/10.1002/hipo.70081.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"rTCT: Rodent Triangle Completion Task to Facilitate Reverse Translational Study of Path Integration","authors":"Stephen Duncan,&nbsp;Sulaiman Rehman,&nbsp;Vladislava Segen,&nbsp;Irene Choi,&nbsp;Sami Lawrence,&nbsp;Om Kalani,&nbsp;Lisette Gold,&nbsp;Lillian Goldman,&nbsp;Sophia Ramlo,&nbsp;Kylene Stickel,&nbsp;Dylan Layfield,&nbsp;Thomas Wolbers,&nbsp;Zoran Tiganj,&nbsp;Ehren L. Newman","doi":"10.1002/hipo.70090","DOIUrl":"10.1002/hipo.70090","url":null,"abstract":"<p>Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimer's disease. In rodents, however, path integration is assessed using a wide variety of tasks, but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study, we developed and tested a novel rodent version of the triangle completion task to enhance cross-species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimer's disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13035483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147581120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}