Hippocampus最新文献

Hippocampal subfields differentially develop and age, and they vary in vulnerability to neurodegenerative diseases. Innovation in high-resolution imaging has accelerated clinical research on human hippocampal subfields, but substantial differences in segmentation protocols impede comparisons of results across laboratories. The Hippocampal Subfields Group (HSG) is an international organization seeking to address this issue by developing a histologically valid, reliable, and freely available segmentation protocol for high-resolution T₂-weighted 3 T MRI (http://www.hippocampalsubfields.com). Here, we report the first portion of the protocol focused on subfields in the hippocampal body; protocols for the head and tail are in development. The body protocol includes definitions of the internal boundaries between subiculum, Cornu Ammonis (CA) 1–3 subfields, and dentate gyrus, in addition to the external boundaries of the hippocampus apart from surrounding white matter and cerebrospinal fluid. The segmentation protocol is based on a novel histological reference dataset labeled by multiple expert neuroanatomists. With broad participation of the research community, we voted on the segmentation protocol via an online survey, which included detailed protocol information, feasibility testing, demonstration videos, example segmentations, and labeled histology. All boundary definitions were rated as having high clarity and reached consensus agreement by Delphi procedure. The harmonized body protocol yielded high inter- and intra-rater reliability. In the present paper we report the procedures to develop and test the protocol, as well as the detailed procedures for manual segmentation using the harmonized protocol. The harmonized protocol will significantly facilitate cross-study comparisons and provide increased insight into the structure and function of hippocampal subfields across the lifespan and in neurodegenerative diseases.

Yonelinas, A. P. 2025. “Unpacking the Medial Temporal Lobe: Separating Recollection and Familiarity.” Hippocampus 35, no. 5: e70033. https://doi.org/10.1002/hipo.70033.

In the original version of this article, the article type was incorrectly listed as “Commentary.” The correct article type is “Review Article.” The online version has been corrected accordingly.

We apologize for this error.

Fenton A. A. 2026. “Overdispersion: Navigating Noise, Learning and Remembering.” Hippocampus 36 no. 1: e70060. https://doi.org/10.1002/hipo.70060.

In the original version of this article, the article type was incorrectly listed as “Commentary.” The correct article type is “Review Article.” The online version has been corrected accordingly.

We apologize for this error.

This paper describes the events leading up to the discovery of the place cells in 1971 for which the author received the Nobel Prize in Physiology and Medicine in 2014, together with May-Britt and Edvard Moser. In addition, it explores some of the ideas and influences that contributed to the interpretation of that finding as evidence for the Hippocampus as a Cognitive Map. Crucial to the acceptance of the idea of place cells and cognitive maps has been the development of recording technologies, and some of these are covered in the middle section. The final section tries to draw some lessons that the author has reached from his experiences.

The hippocampal formation is a functional entity that includes the hippocampus, subicular complex, and the entorhinal cortex, and has an essential role in learning and memory, emotional processing, and spatial coding. The well-defined structure of hippocampal fields and the segregation of the connections have made this structure a favorite candidate for functional models that rely on fundamental information such as the number of neurons populating the hippocampal fields. Existing models on the rat rely on neuronal populations obtained from single studies, so we aimed to obtain more representative estimates by analyzing all available data. We identified 89 studies using reliable methodology that provided 264 stereological estimates of principal neuron populations. The resulting averages for males showed 1,000,000 neurons for the granule cell layer (GCL); 50,000 for the hilus; 210,000 for CA3; ~30,000 for CA2; 350,000 for CA1; and 300,000 for the Subiculum. Entorhinal cortex (EC) averages for both sexes showed 108,000 neurons in layer II; 270,000 in layer III; and 340,000 in layer V/VI. Most of those estimates are significantly different from those traditionally used in hippocampal models (e.g., ~2-fold difference in EC layer II), revealing an updated architecture of the rat hippocampal formation that might help build more realistic models of hippocampal connectivity and function. Comparisons by age or sex were not reliable given the scarce data available from adolescents or females, while comparisons by strain showed inconsistent results, with similar populations in most fields but significant differences in CA3/CA2. The reliability of this finding is discussed.

Traumatic brain injury (TBI) is a leading cause of long-term disability, with limited effective treatment options. A key factor of TBI pathophysiology is neuroinflammation, which can involve the activation of the nucleotide-binding domain leucine-rich repeat protein 3 (NLRP3) inflammasome. Aberrant inflammation following injury has the ability to reduce the capacity to induce long-term changes in synaptic plasticity, a leading mechanism for the development of learning and memory deficits following injury. This study investigated the potential of a novel NLRP3 inhibitor, AMS-17, to mitigate synaptic plasticity deficits following mild TBI (mTBI) in mice. Adult C57Bl/6 mice were subjected to mTBI or a sham injury, and hippocampal slices were then prepared for field electrophysiological recordings in the medial perforant pathway of the dentate gyrus. We found that mTBI induced deficits in long-term potentiation that were not immediate at 2 h post-injury but developed by 3 days post-injury. We next incubated slices in AMS-17 or a control solution prior to electrophysiological recordings. Here we found that incubation with AMS-17 rescued these LTP deficits, bringing them to levels observed in sham-injured controls. Importantly, AMS-17 did not affect the capacity to induce LTP in sham-injured mice. These findings suggest that targeting the NLRP3 inflammasome may offer a promising therapeutic strategy to reduce learning and memory impairments following mTBI. Further studies are needed to determine the optimal therapeutic window and long-term efficacy of AMS-17 in mTBI.

I describe my progress in understanding synaptic plasticity in the hippocampus. Over the decades my lab has focused on the roles of glutamate receptors (AMPARs, NMDARs, mGluRs and KARs) and associated signaling molecules in LTP and LTD. Most of our studies have been conducted in area CA1 (Schaffer collateral—commissural pathway) with some conducted in CA3 (mossy fiber pathway). We have made extensive use of electrophysiology and pharmacological tools, complemented with knock-out (KO) and transgenic mice, biochemistry and dynamic imaging. From a starting point in 1980, with essentially no molecular insights available, we have developed a detailed, but still incomplete, mechanism for LTP at CA1 and CA3 synapses as well as providing insights into LTD at CA1 synapses. We have also explored how dysregulated synaptic plasticity contributes to brain disorders, with an emphasis on Alzheimer's disease. Indeed, through a molecular understanding of synaptic plasticity, now we can explain how plaques and tangles are related mechanistically and, in essence, how the early stages of dementia are triggered. Therapeutic strategies, both pharmacological and lifestyle, for tackling dementia are touched upon. Our work, together with that of many other groups, has resulted in massive progress in the understanding of synaptic plasticity in the mammalian CNS in health and disease.