Hippocampus最新文献

{"title":"An Update on the Model of Connectivity of the Hippocampal Formation (I): The Perforant Pathway to the Dentate Gyrus","authors":"Jon I. Arellano,&nbsp;Pasko Rakic","doi":"10.1002/hipo.70114","DOIUrl":"https://doi.org/10.1002/hipo.70114","url":null,"abstract":"<p>The hippocampus participates in crucial functions such as memory consolidation, spatial processing and emotional regulation that require diverse input from multiple cortical areas that is funneled through the upper layers of the entorhinal cortex (EC), mostly from layer II to the dentate gyrus (DG). Traditional models of the hippocampal formation described 200,000 EC layer II neurons projecting to 1 million granule cells (GCs) in the rat, rendering low divergence (1:5), with each EC neuron establishing about 18,000 synapses with GCs and each GC receiving about 4000 synapses from EC neurons. In this manuscript, we update this model of connectivity incorporating new features described in the last three decades that include updated populations of EC layer II neurons obtained with design-based stereology, a revised definition of EC layer II based on molecular criteria and selecting reelin expressing neurons as the only layer II neurons projecting to the hippocampus. The updated model shows ~80,000 neurons from EC layer II projecting to the DG, ~45,000 from the medial entorhinal cortex (MEC) and ~35,000 from the lateral entorhinal cortex (LEC) with high divergence of 1:20 and 1:30. We also show that EC layer II neurons may establish ~90,000–115,000 synapses on GCs, while GCs receive about 8000 synapses from EC layer II neurons. We estimate a ~25% redundancy in the connectivity, so each EC neuron may contact ~68,000–86,000 GCs and each GC would be contacted by ~3000 neurons from MEC and 3000 from LEC. In addition, we quantitatively assess a potential projection of mossy cells to the middle molecular layer described in mice, which could have an impact on GC inhibition. Overall, we produced a detailed, complete, and updated quantitative model of EC projections to the DG that reveals a much more divergent and richer projection than previously described, with implications for functional models (e.g., pattern separation) and more widely for building realistic hippocampal models or establishing comparisons across species.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652407","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":"Hippocampus–Ventral Striatum Connectivity Is Associated With Binge Drinking Frequency in Adults","authors":"Blake L. Elliott,&nbsp;Zeeshan M. Huque,&nbsp;Nicholas A. Ruiz,&nbsp;Lauren M. Ellman,&nbsp;Vishnu P. Murty","doi":"10.1002/hipo.70113","DOIUrl":"10.1002/hipo.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>Contextual information, such as spatial locations and social groups, are known to propagate reward-seeking behavior including binge drinking. Animal models suggest that context-evoked drug and alcohol seeking emerges from hippocampal projections to the ventral striatum (i.e., nucleus accumbens). While binge drinking has been associated with adverse structure and function of both the ventral striatum and hippocampus, the anatomical relevance of this circuit in humans has largely been inferred from volumetric studies investigating these regions separately. Using diffusion MRI tractography in adults ages 22–35 (<i>N</i> = 593), we examined hippocampal–ventral striatum (HPC-VS) connectivity in relation to binge drinking. We found that greater left hemisphere HPC-VS connectivity was associated with greater past-year binge drinking frequency (<i>b</i> = 0.17, <i>p</i> = 0.027). In the right-hemisphere, an HPC-VS × sex interaction emerged for binge drinking frequency (<i>b</i> = 0.17, <i>p</i> = 0.031), such that greater right-hemisphere connectivity was associated with greater binge drinking frequency in females but lower binge drinking frequency in males. These findings demonstrate hemisphere- and sex-specific associations between hippocampal-striatal pathways and alcohol use, implicating structural variability in this circuit as a correlate of vulnerability to alcohol consumption that may be problematic.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591286","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":"Myosin IIB Maintains Long-Term Memory","authors":"Mateus Oliveira Silva,&nbsp;Lucas Aschidamini Marcondes,&nbsp;Paula Lunardi,&nbsp;Bruno Popik,&nbsp;Rossana Rosa Porto,&nbsp;Marina da Silva Medeiros,&nbsp;Lucas de Oliveira Alvares","doi":"10.1002/hipo.70112","DOIUrl":"10.1002/hipo.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>Synaptic plasticity and memory are intrinsically linked to the dynamics of dendritic spines. The protein myosin IIB is central to the morphology and physiology of dendritic spines and thereby regulates synaptic plasticity. In this study, we used specific inhibitors of myosin IIB, blebbistatin (Blebb) and para-nitro-blebbistatin (p-N-Blebb), to assess its role in memory. We found that inhibiting myosin IIB in the hippocampus impairs long-term fear memory consolidation, but not short-term memory, and that pretest blockade hinders memory retrieval. Remarkably, we observed that blocking myosin IIB activity in the hippocampus, amygdala, or insular cortex 24 h after training impairs distinct consolidated memories, suggesting that myosin IIB plays an essential role in memory maintenance. Our results show that myosin IIB activity is crucial not only for memory formation and expression but also for memory storage, likely by preserving dendritic spines after learning.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520316","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":"Opioid-Associated Hippocampal Injury: Past, Present, and Future Directions","authors":"Jed A. Barash,&nbsp;Joshua Madden,&nbsp;W. Andrew Kofke","doi":"10.1002/hipo.70111","DOIUrl":"10.1002/hipo.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Three of the great public health challenges of our time converge at the hippocampus. The first, dementia, most commonly in the form of Alzheimer's disease, is well known to cause progressive hippocampal damage, resulting in the memory loss associated with the illness. The second, COVID-19 infection, has thus far been linked to hippocampal alterations across multiple studies. Lastly, the third, opioids—especially in the setting of misuse—have been associated with acute and persistent hippocampal injury; this review focuses on the collection of pre-clinical, clinical, and epidemiologic observations supporting this final relationship. Basic science work dating back decades has demonstrated a hypermetabolic response to opioids and associated damage to the hippocampus. The earliest cases recognized as opioid-associated amnestic syndrome (OAS) were subsequently identified in 2012 and reported as part of larger case series several years later. In 2019, a related but more fulminant syndrome involving cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER) was first described. From these investigations, a growing body of data has since emerged to suggest that regular opioid use, particularly at higher doses or potency, may be connected to a reduction in hippocampal volume and greater risk of dementia. This review begins with a synthesis of data supporting the underlying pathological mechanisms of opioid-associated hippocampal injury (OAHI), then covers the clinical spectrum of this phenomenon. Lastly, we will close with implications of OAHI that warrant further study, including the future epidemiologic impact on related cognitive disorders in the wake of the opioid epidemic and potential therapeutic applications of opioid antagonism for mild cognitive impairment.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301587","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":"Neural and Navigational Features Influencing the Novelty Induced Benefits on Episodic Memory","authors":"David A. Vogelsang,&nbsp;Carla Maló Calmus,&nbsp;Madeleine Vohs,&nbsp;Kreeta I. L. Kerkkänen,&nbsp;Svetlin Hansov,&nbsp;Judith Schomaker","doi":"10.1002/hipo.70109","DOIUrl":"10.1002/hipo.70109","url":null,"abstract":"<p>Studies in animals have robustly shown that exposure to novelty can promote memory for information presented in the temporal vicinity. In humans, however, evidence for such novelty-related memory benefits has been mixed. In this EEG study, we investigated the neurobiological mechanisms underlying effects of novelty on memory and whether individual differences in exploration patterns help explain these inconsistencies. We examined the role of theta oscillations in exploring a novel or familiar environment as well as whether spatial exploration behavior can modulate the beneficial effects of novelty on memory. Participants first explored one of two virtual environments and subsequently explored the same (familiar condition) or a new environment (novel condition). After exploring novel and familiar environments, participants performed a word learning task followed by a free recall and recognition memory test. Neurologically, exploration of the familiar rather than novel environment increased theta power, which may reflect environment-related memory processes. However, we did not observe any differences in theta power associated with successful encoding of words after exploring a novel versus familiar environment. Behaviorally, no main effect of novelty on free recall was observed. Crucially, when accounting for variance in spatial exploration patterns, words encoded after exploring a novel environment were recalled better than words encoded after exploring a familiar environment. Furthermore, an interaction effect between the condition and exploratory behavior revealed that increased exploration benefitted free recall specifically in the familiar condition. These findings emphasize the importance of considering the way in which individuals explore a virtual environment when examining novelty effects on memory.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271256","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":"Intrinsic Persistent Firing in CA1 Encodes Elapsed Time Across Behaviorally Relevant Scales","authors":"Sara Zomorodi,&nbsp;Beate Knauer,&nbsp;Yacine Brahimi,&nbsp;Antonio Reboreda,&nbsp;Motoharu Yoshida,&nbsp;Zoran Tiganj","doi":"10.1002/hipo.70105","DOIUrl":"10.1002/hipo.70105","url":null,"abstract":"<div>\u0000 \u0000 <p>The ability to encode and maintain temporal relationships is crucial for learning, predicting, and forming episodic memories. While hippocampal time cells and entorhinal temporal context cells are well-established in vivo, it remains unclear whether single neurons can sustain representations of elapsed time over multi-second intervals, independent of synaptic drive. Here, using whole-cell patch-clamp recordings in rat hippocampal CA1 slices under synaptic blockade, we show that following a brief current pulse, many neurons exhibit exponentially decaying firing rates with a broad distribution of time constants extending to tens of seconds. This indicates that single neurons possess intrinsic mechanisms capable of covering behaviorally relevant temporal scales. These results highlight that single neurons can encode temporal information over more than an order of magnitude, providing a potential cellular substrate for temporal coding in the brain.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251357","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":"Issue Information - Editorial Board","authors":"","doi":"10.1002/hipo.70106","DOIUrl":"https://doi.org/10.1002/hipo.70106","url":null,"abstract":"","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203046","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":"Boundary Vector Cells Encode a Future-Biased Spectrum of Positions in the Rat","authors":"Ehren Lee Newman,&nbsp;Inna Mashanova-Galikova,&nbsp;Zoran Tiganj,&nbsp;Colin Lever","doi":"10.1002/hipo.70110","DOIUrl":"https://doi.org/10.1002/hipo.70110","url":null,"abstract":"<p>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 toward 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 boundary vector cells (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.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 4","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148203047","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148087927","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148089180","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}