HippocampusPub Date : 2026-05-01DOI: 10.1002/hipo.70103
Nicole C Reyna, Derek A Hamilton
{"title":"Effects of Corticotropin-Releasing Factor 1 Receptor Antagonism on In Vivo Dentate Gyrus Long-Term Potentiation in the TgF344-AD Rat Model of Alzheimer's Disease.","authors":"Nicole C Reyna, Derek A Hamilton","doi":"10.1002/hipo.70103","DOIUrl":"10.1002/hipo.70103","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterized by irreversible neurobiological deterioration and cognitive impairment. AD patients exhibit stress system abnormalities including upregulation of the corticotropin releasing factor type 1 receptor (CRF<sub>1</sub>) and elevated cortisol. Psychological distress increases the likelihood of AD diagnosis and hastens neurocognitive decline. Administration of the CRF<sub>1</sub> antagonist, Antalarmin, reduces AD pathogenesis and anxiety-like behavior in models of AD. Motivated by these observations, the current study examined the potential contributions of CRF<sub>1</sub> to altered synaptic plasticity in AD neuropathology and stress in the TgF344-AD rat model. In vivo electrophysiological recordings to assess long-term potentiation (LTP) in the perforant pathway to dentate gyrus synapses were performed in aged transgenic rats and wild-type (WT) controls (2-2.5 years). TgF344-AD rats had abnormal LTP measures of field excitatory post-synaptic potentials (fEPSP) and population spikes (PS). Treatment with Antalarmin did not alter LTP measures in TgF344-AD or WT rats. These observations indicate that LTP in TgF344-AD rats is reduced compared to WT rats and that acute treatment with a CRF<sub>1</sub> antagonist did not rescue LTP deficits. Future research should further examine the mechanism of CRF<sub>1</sub> in AD and implications of agonism or direct infusions of Antalarmin in vivo.</p>","PeriodicalId":13171,"journal":{"name":"Hippocampus","volume":"36 3","pages":"e70103"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981649","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}
HippocampusPub Date : 2026-05-01DOI: 10.1002/hipo.70102
Su-Min Lee, Inah Lee
{"title":"Encoding Patterned Spatial Behavior in the Subiculum.","authors":"Su-Min Lee, Inah Lee","doi":"10.1002/hipo.70102","DOIUrl":"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":2.9,"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}
HippocampusPub Date : 2026-05-01DOI: 10.1002/hipo.70097
Paula Gonçalves Vieira Teixeira, Leonardo de Oliveira Guarnieri, Grace Schenatto Pereira, Márcio Flávio Dutra Moraes
{"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":2.9,"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}
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