Hippocampus最新文献

{"title":"Homeostatic Control of Hebbian Plasticity Exerted by Action Potential-Mediated Metaplasticity","authors":"Giuseppe Busetto,&nbsp;Bruce G. Mockett,&nbsp;Alessandro Marcon,&nbsp;Wickliffe C. Abraham","doi":"10.1002/hipo.70140","DOIUrl":"10.1002/hipo.70140","url":null,"abstract":"<div>\u0000 \u0000 <p>Hebbian plasticity, in particular long-term potentiation (LTP) of excitatory synapses, is a positive feed-back mechanism and has the potential to saturate its effects with negative consequences at both the single neuron and the circuit level. Metaplasticity is one of the mechanisms that can help overcome this problem. During one form of metaplasticity, a high (or low) level of neuronal activity impedes (or favors) the expression of future LTP. Although much is known about the role of synaptic activity in driving this metaplasticity effect, the specific role of postsynaptic action potential (AP) firing activity is still controversial and largely unknown. Experimentally, a high level of AP firing has resulted in either the suppression (a pro-homeostatic effect) or the enhancement (an anti-homeostatic effect) of a later induced LTP. Accordingly, we tested a wide range of AP firing frequencies generated by postsynaptic current pulses at different time intervals relative to the time of LTP induction at Schaffer collateral synapses of hippocampal CA1 neurons in Sprague–Dawley rats. We found that a wide range of AP firing frequencies, from 3 to 90 Hz, consistently inhibited the expression of future LTP at all time intervals tested, with no modulation of NMDA glutamate receptors. Moreover, the generation of APs, as opposed to the average level of somatic depolarization during priming, was necessary for triggering the metaplasticity. Our results provide solid evidence for a pro-homeostatic metaplasticity that is engaged by postsynaptic AP firing, thus impeding the saturation of Hebbian plasticity and associated hyperexcitability.</p>\u0000 </div>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181257","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":"Chronic Electroconvulsive Shock Disrupts Hippocampal Physiology and Impairs Associative Memory in Mice","authors":"T. R. Zhang,&nbsp;N. P. Vyleta,&nbsp;I. Schwein,&nbsp;B. Askari,&nbsp;M. B. Cooke,&nbsp;F. Vila-Rodriguez,&nbsp;J. S. Snyder","doi":"10.1002/hipo.70142","DOIUrl":"10.1002/hipo.70142","url":null,"abstract":"<p>Electroconvulsive therapy (ECT) is a highly effective treatment for depression but it has undesirable side effects on various aspects of cognition, including memory. Patients may display retrograde amnesia for autobiographical events and anterograde amnesia in tests of recall and recognition memory. These amnestic effects are likely to depend, at least in part, on changes in the hippocampus. ECT-induced volume increases in the hippocampus and dentate gyrus subregion in particular correlate with the cognitive deficits. However, the precise cellular and behavioral effects of ECT remain poorly understood. Here, we therefore subjected male and female mice to chronic electroconvulsive shock (ECS) and examined effects on hippocampal physiology and memory. Perforant path inputs onto dentate gyrus neurons were examined using whole cell patch clamp recordings in hippocampal slices. In the intact slice, perforant path stimulation did not result in any synaptic or spiking differences in mice given sham versus ECS treatments. However, GABA_A blockade increased EPSPs and spiking in sham, but not ECS-treated, mice. Voltage clamp recordings further revealed weaker perforant path excitation of dentate gyrus neurons in ECS-treated mice. Extrapolating these findings to the intact animal, we then used Fos expression as a proxy for neural activity and found that ECS blunted exploration-induced hippocampal activation, which was most pronounced in the dentate gyrus. Finally, recognition memory tasks revealed that ECS impaired memory for object-context associations but not memory for objects or locations. Collectively, these experiments reveal that a clinically relevant schedule of ECS disrupts synaptic and circuit functions of the hippocampus and causes anterograde amnesia in a test of episodic-like associative memory.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181299","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":"Mapping Projectome Heterogeneity of Subiculum Neuron Cell Types","authors":"Ann W. Saustad,&nbsp;Michael S. Bienkowski","doi":"10.1002/hipo.70138","DOIUrl":"10.1002/hipo.70138","url":null,"abstract":"<p>The subiculum (SUB) is the main output structure of the hippocampus, influencing diverse behaviors through its widespread cortical and subcortical connections. Our previous work creating the mouse Hippocampus Gene Expression Atlas (HGEA) identified four genetically distinct cellular layers across five columnar domains in the SUB, with gene expression boundaries corresponding to distinct connectivity patterns and brain-wide networks involved in spatial navigation, social behavior, and neuroendocrine regulation. Using the Digital Brain Mouse Projectome Atlas (MPA) tool, we conducted ‘virtual tract-tracing’ to assess whether connectivity patterns of single-neuron 3D reconstructions aligned with HGEA-defined SUB cell types. We classified 689 SUB projection neurons into 12 HGEA cell-type groups based on their laminar and columnar distributions, whose spatial organization recapitulated HGEA-defined 3D boundaries. Using this population sample, we performed a SUB cell-type census, characterized neuronal heterogeneity and projection prevalence, identified common and rare connectivity motifs and axonal collateralization patterns, and defined distinct projection themes for each SUB cell type. Together, this analysis integrates single-neuron and population-level data to advance understanding of SUB cell type organization and its contributions to brain-wide networks regulating diverse behaviors.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181417","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":"Temporal Interference Modulates Medial Temporal and Frontoparietal Activity During Mnemonic Discrimination: A High-Resolution Whole-Brain fMRI Investigation","authors":"Min Sung Seo,&nbsp;Rebecca L. Wagner,&nbsp;Jordan D. Chamberlain,&nbsp;Kelsey L. Canada,&nbsp;Nancy A. Dennis","doi":"10.1002/hipo.70137","DOIUrl":"10.1002/hipo.70137","url":null,"abstract":"<p>Mnemonic discrimination—the ability to distinguish between existing memories and similar new inputs—supports accurate memory in the face of interference (e.g., in a card game, recognizing that the card you are currently seeing, the King of Hearts, is distinct from the King of Diamonds you encountered earlier in the same hand). Although hippocampal pattern separation has been emphasized as a key mechanism for this process, recent theoretical frameworks and empirical findings suggest that surrounding medial temporal lobe and cortical regions also contribute by resolving interference. An important source of interference in everyday life is temporal interference: similar events may compete not only because they overlap perceptually, but also because they are separated by intervening experiences (e.g., distinguishing the King of Hearts you are currently holding in your hand from the King of Diamonds you encountered earlier in the game becomes increasingly difficult as additional cards are played and additional hands intervene between the two episodes). Here, we examined how temporal interference impacts mnemonic discrimination and its neural correlates using high-resolution fMRI and a continuous recognition task in which the lag between an item's first presentation and its subsequent target or similar lure was systematically manipulated (10, 60, or 140 intervening trials). Behaviorally, increasing lag impaired both mnemonic discrimination and target recognition. At the neural level, lag effects were not observed in hippocampal subfields. Instead, temporal interference modulated activity in extrahippocampal MTL regions including parahippocampal and perirhinal cortex, as well as distributed cortical regions including frontoparietal control areas. Importantly, lag-related modulation was process-specific, with partially dissociable patterns for successful mnemonic discrimination and target recognition. Together, these findings demonstrate that temporal interference engages a distributed MTL-cortical network that supports interference resolution during mnemonic discrimination.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108941","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":"Adolescent Ethanol Exposure Disrupts the Mature Phenotype of Surviving Neuroprogenitors in Female Mice","authors":"Kaitlyn Campbell,&nbsp;Madison McDowell,&nbsp;Eymani Alston,&nbsp;Hunter Kelley,&nbsp;Michael Kasten,&nbsp;Paul B. Manis,&nbsp;Fulton Crews,&nbsp;Victoria Macht","doi":"10.1002/hipo.70134","DOIUrl":"10.1002/hipo.70134","url":null,"abstract":"<p>Rodent models of human adolescent binge drinking persistently reduce adult neurogenesis and induce innate immune signaling cascades, suggesting long-lasting dysfunction in the hippocampal neurogenic niche. Nevertheless, many neuroprogenitors survive, and the impact of adolescent ethanol on the mature phenotype of these surviving neurons is unknown, resulting in an unstudied cellular population that could impact hippocampal function. To label a cohort of immature neurons, we used doublecortin-CreERT2 transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, resulting in tamoxifen-induced labeling of newborn neurons. Female offspring underwent adolescent intermittent ethanol (AIE) (5 g/kg ethanol or water by gavage, 2-day-on/2-day-off from postnatal day 29–58 ± 1), followed by a multi-month ethanol-free period. AIE increased dendritic branch width and cellular migratory distance, increased hilar axonal varicosities, reduced dendritic spine density, and shifted action potential generation with escalating current injections in tdTomato+ cells. Although tdTomato+ expression was also decreased in AIE relative to CON mice, there was no significant change in the number of tdTomato+ somata. AIE also reduced microglial territory in the polymorphic and molecular layers despite no change in cell number. Furthermore, microglia entwined in the dendritic trees of surviving adolescent neuroprogenitors exhibited increased sphericity, potentially indicative of a shift towards a more reactive morphological phenotype. Surviving neuroprogenitors exhibited no changes in labeling of the vesicular acetylcholine transporter, despite robust cholinergic innervation proximal to the mature dendritic tree that reduced rapidly with increasing distance from dendritic arbors. These results suggest that AIE causes lasting changes in the architectural and physiological phenotype of surviving adolescent neuroprogenitors, which may be related to disrupted neuronal-microglial dynamics and have critical consequences for both hippocampal circuitry and function.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628545/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109006","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":"Mental Scene and Memory Construction and the Hippocampus","authors":"Edmund T. Rolls","doi":"10.1002/hipo.70136","DOIUrl":"https://doi.org/10.1002/hipo.70136","url":null,"abstract":"<p>A neurocomputational theory of scene and memory construction during memory recall, prospective thinking, and autobiographical memory is described. The theory describes the nature of the representation of scenes using spatial view cells in a continuous attractor network in the medial parahippocampal cortex, and how the location in the scene being represented can be shifted by self-motion eye position update even when the scene is not visible. The theory builds on the evidence for humans for a ventromedial visual cortical scene pathway via the prostriate cortex and ventromedial visual cortical regions to the medial parahippocampal scene (or place) area where scenes are represented. The approach builds on a theory about how visual features in scenes are used along this pathway to build a continuous attractor network representation of scenes in the medial parahippocampal cortex that represents the relative spatial locations of features or landmarks in the scene. The theory shows how episodic memory can be built in an attractor network in hippocampal CA3 that learns associations between the location in a scene (“where”), the object or person at that location in the scene (“what”), and the reward/affective value conveyed to the hippocampus from the orbitofrontal cortex in part via the ventromedial prefrontal cortex and posterior cingulate cortex. The theory of scene construction then shows how backprojections from hippocampal CA1 via the entorhinal cortex to the medial parahippocampal cortex can recall or construct the scene representation in the medial parahippocampal cortex, the parahippocampal scene (or place) area; and how whole memories including visual imagery of objects, rewards, and their locations in scenes can be constructed by iterative neocortical-hippocampal-neocortical processing.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068250","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":"Issue Information - Editorial Board","authors":"","doi":"10.1002/hipo.70108","DOIUrl":"https://doi.org/10.1002/hipo.70108","url":null,"abstract":"","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 6","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149068251","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 Branching Projection Pattern of Ventral Subicular Cells Revealing the Complex Integrative Role of Key Hippocampal Outputs in Driving Fear and Anxiety","authors":"Fernando Falkenburger Melleu,&nbsp;Karolina Domingues,&nbsp;Isadora D'Ávila Tassinari,&nbsp;Newton Sabino Canteras","doi":"10.1002/hipo.70128","DOIUrl":"10.1002/hipo.70128","url":null,"abstract":"<p>The ventral regions of the hippocampus play a crucial role in emotional responses through projections to the hypothalamus. In this context, the ventral hippocampus sends extensive projections to components of the medial hypothalamic defensive circuit, where projections to the anterior hypothalamic nucleus (AHN) influence both anxiogenic and innate fear responses, as well as contextual fear reactions. This study aims to examine the branching projection pattern of hippocampal cells that directly project to the AHN and identify the complete range of brain regions affected by key hippocampal outputs that drive fear and anxiety. To accomplish this, we first explored the full range of hippocampal cells that project directly to the anterior hypothalamic area using an AAV retroviral vector carrying the enhanced yellow fluorescent protein (EYFP) reporter gene. We found that the hippocampal cells projecting to the anterior hypothalamus were located primarily along the entire rostro-caudal axis of the ventral subiculum. Next, by combining an AAV retro vector injection into the AHN to insert Cre recombinase specifically in the subicular neurons projecting to the anterior hypothalamic region and subicular injections of an AAV vector expressing membrane-bound GFP and the presynaptic protein synaptophysin fused to the red fluorescent protein mRuby in a Cre-dependent manner, we investigated the collateral branching pattern of subicular neurons that project to the AHN. Our results demonstrated that ventral subicular neurons projecting to the anterior hypothalamus exhibit an extensive branching projection pattern that connects to several brain regions involved in various functions, including memory, motivation, arousal, circadian rhythmicity, neuroendocrine regulation, and goal-oriented behavior. This reveals that ventral subicular anterior hypothalamic-projecting cells display a widespread branching projection pattern, uniquely positioning them to influence complex, integrated responses while driving anxiety and fear behaviors.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012183","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":"Impaired Synaptic Plasticity in a Rodent Model of Intimate Partner Violence-Related Brain Injury","authors":"Justin Brand,&nbsp;Eric Eyolfson,&nbsp;Kirsten R. B. Suesser,&nbsp;Emma S. J. Smith,&nbsp;Zoe L. Thompson,&nbsp;Stuart J. McDonald,&nbsp;Jodie R. Gawryluk,&nbsp;Sandy R. Shultz,&nbsp;Brian R. Christie","doi":"10.1002/hipo.70135","DOIUrl":"10.1002/hipo.70135","url":null,"abstract":"<p>Intimate partner violence-related brain injury (IPV-BI) predominantly affects women and often reflects both structural trauma from mild traumatic brain injury (mTBI), as well as ischemia/hypoxia from non-fatal strangulation (NFS). This polytrauma can impair cognitive function, particularly learning and memory processes, which may contribute to the continuation of the cycle of violence. This study investigates the effects of mTBI and hypoxic/ischemic injury on hippocampal long-term potentiation (LTP), a biological model of learning and memory, to determine if the combination of mTBI+NFS would exacerbate deficits in LTP. Female rats were randomly assigned to either Sham, mTBI, NFS, or mTBI+NFS groups to assess acute injury metrics and LTP capacity 7 days after injury. At the time of injury, NFS and mTBI+NFS groups exhibited significant reductions in blood oxygen saturation, heart rate, and poor neurological assessment metrics. Isolated mTBI and NFS impaired LTP in the CA1 hippocampal region while mTBI+NFS increased synaptic excitability in the CA1 yet impaired CA1 LTP. Contrary to our hypothesis, the combined mTBI+NFS did not exacerbate deficits, but these findings highlight that even a single episode of mTBI or NFS is sufficient to impair hippocampal LTP in the female CA1 region.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590904/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012150","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":"Decoding Medial Entorhinal Cortical Dynamics Produces Planning-Like Alternations in Hippocampal theta Sequences","authors":"Masahiro Nakano,&nbsp;Caswell Barry,&nbsp;Claudia Clopath","doi":"10.1002/hipo.70131","DOIUrl":"https://doi.org/10.1002/hipo.70131","url":null,"abstract":"<p>The hippocampus is central to memory and spatial planning. A prominent candidate mechanism supporting navigational decision making is hippocampal theta sequences—brief (~120 ms) place-cell sequences representing future trajectories—which have been interpreted as planning signals based on their alternation between maze arms in T-maze tasks. However, recent work suggests that intrinsic left–right alternation in medial entorhinal cortex (MEC) theta sequences may underlie this phenomenon. Here, we test this hypothesis using a model of MEC theta dynamics in a T-maze and show that standard Bayesian decoding yields hippocampal theta sequences that alternate between arms. We then analyzed existing simultaneous MEC-hippocampal recordings from Vollan et al. (2025). We found tight coupling between MEC and hippocampus, along with coordinated left–right alternation, while the animal was performing an alternation task. Notably, this conjoint alternation occurs not only at choice points but also during inbound and forced-turn trials. These findings suggest that left–right alternation in hippocampal theta sequences is a ubiquitous phenomenon driven by MEC dynamics, challenging the interpretation that these specifically reflect intentional decision-making or planning processes only.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 5","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hipo.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148994458","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}