Hippocampus最新文献

Adult hippocampal neurogenesis (AHN) is the process by which new neurons are continuously generated from neural stem and progenitor cells (NSPCs) in the adult dentate gyrus. AHN plays a pivotal role in cognitive functions, including learning, memory, and mood regulation. Transcription factors regulate AHN by maintaining the NSPC pool and facilitating lineage progression. The nuclear factor I (NFI) transcription factor family member NFIA is critical for neurogenesis and gliogenesis during early brain development, but its role in adult neurogenesis remains poorly understood. Here, we generated an inducible Nfia loss-of-function mouse model to investigate the role of NFIA in Ascl1-lineage adult-born neurons. By tracking lineage progression from NSPCs to mature neurons, we found that NFIA deletion significantly reduced neurogenesis. Populations of NSPCs, neuroblasts, and mature granule neurons were all similarly diminished, indicating a primary defect in NSPC maintenance. Behaviorally, NFIA loss impaired hippocampal-dependent contextual fear memory without affecting locomotor activity, anxiety levels, spatial memory, or cued fear memory. Our findings demonstrate that NFIA is crucial for AHN and hippocampus-dependent contextual memory, thereby providing insights into its role in adult neurogenesis.

A longstanding principle in episodic memory research, known as the encoding specificity hypothesis, holds that an effective retrieval cue should closely match the original encoding conditions. This principle assumes that a successful retrieval cue remains static over time. Despite the broad acceptance of this idea, it conflicts with one of the most well-established findings in memory research: The dynamic and ever-changing nature of episodic memories. In this article, we propose that the most effective retrieval cue should engage with the current state of the memory, which may have shifted significantly since encoding. By redefining the criteria for successful recall, we challenge a core principle of the field and open new avenues for exploring memory accessibility, offering fresh insights into both theoretical, and applied domains.

The dentate gyrus subfield of the hippocampus is thought to be critically involved in the disambiguation of similar episodic experiences and places in a context-dependent manner. However, most empirical evidence has come from lesion and gene knock-out studies in rodents, in which the dentate gyrus is permanently perturbed and compensation of affected functions via other areas within the memory circuit could take place. The acute and causal role of the dentate gyrus herein remains therefore elusive. The present study aimed to investigate the acute role of the dorsal dentate gyrus in disambiguation learning using reversible inhibitory DREADDs. Rats were trained on a location discrimination task and learned to discriminate between a rewarded and unrewarded location with either small (similar condition) or large (dissimilar condition) separation. Reward contingencies switched after applying a reversal rule, allowing us to track the temporal engagement of the dentate gyrus during the task. Bilateral DREADD modulation of the dentate gyrus impaired the initial acquisition learning of place-reward associations, but performance rapidly recovered to baseline levels within the same session. Modeling of the behavioral patterns revealed that reward sensitivity and alternation behavior were temporally associated with the DG-dependent impairment during acquisition learning. Our study thus provides novel evidence that the dorsal dentate gyrus is acutely engaged during the initial acquisition learning of place-reward associations.

A theory and network model are presented of how scene representations are built by forming spatial view cells in the ventromedial visual cortical scene pathway to the hippocampus in primates including humans. Layer 1, corresponding to V1–V4, connects to Layer 2 in the retrosplenial scene area and uses competitive learning to form visual feature combination neurons for the part of the scene being fixated, a visual fixation scene patch. In Layer 3, corresponding to the parahippocampal scene area and hippocampus, the visual fixation scene patches are stitched together to form whole scene representations. This is performed with a continuous attractor network for a whole scene made from the overlapping Gaussian receptive fields of the neurons as the head rotates to view the whole scene. In addition, in Layer 3, gain modulation by gaze direction maps visual fixation scene patches to the correct part of the whole scene representation when saccades are made. Each neuron in Layer 3 is thus a spatial view cell that responds to a location in a viewed scene based on visual features in a part of the scene. The novel conceptual advances are that this theory shows how scene representations may be built in primates, including humans, based on features in spatial scenes that anchor the scene representation to the world being viewed (to allocentric, world-based, space); and how gaze direction contributes to this. This offers a revolutionary approach to understanding the spatial representations for navigation and episodic memory in primates, including humans.

Early midlife bilateral salpingo-oophorectomy (BSO) is associated with greater Alzheimer's disease risk compared to spontaneous/natural menopause. Previously, we found that participants with BSO had lower volume in the hippocampal dentate gyrus and cornu ammonis 2/3 composite subfield (DG-CA2/3). We sought to extend those hippocampal subfield findings by assessing whether BSO affected volumes along the anteroposterior hippocampal axis, anterolateral entorhinal cortex, and perirhinal cortex subregions (Brodmann area (BA) 35 and 36). We also correlated volumes with key demographic and wellbeing-related factors (age, depressive mood, education), hormone therapy characteristics, and recognition memory performance. Early midlife participants with BSO (with and without 17β-estradiol therapy (ET)) and age-matched control participants with intact ovaries (AMC) completed high-resolution T2-weighted structural magnetic resonance imaging (MRI). Medial temporal lobe volumes and Remember-Know task recognition memory performance were compared between groups—BSO (n = 23), BSO + ET (n = 28), AMC (n = 34) using univariate analyses. Multivariate Partial Least Squares (PLS) analyses were used to examine how volumes related to demographic and wellbeing-related factors, as well as hormone therapy characteristics. Relative to BSO + ET, BSO had lower posterior hippocampal and DG-CA2/3 volumes but greater perirhinal BA 36 volumes. Compared to age, depressive mood, and education, ET was the strongest positive predictor of hippocampal volumes and negative predictor of perirhinal BA 36 volumes. For BSO + ET, hippocampal volumes were negatively related to ET duration and positively related to concurrent progestogen therapy. Relative to AMC, BSO had greater anterolateral entorhinal cortex and perirhinal BA 35 and BA 36 volumes. BSO groups (with and without ET) relied more on familiarity than recollection for successful recognition memory. BSO and ET may have distinct effects on medial temporal lobe volumes, with potential implications for memory processes affected by Alzheimer's disease risk.

The ability to form different neural representations for similar inputs is a central process of episodic memory. Although the dorsal dentate gyrus and CA3 have been indicated as important in this phenomenon, the neuronal circuits underlying spatiotemporal memory processing with different levels of spatial similarity are still elusive. In this study, we measured the expression of the immediate early gene c-Fos to evaluate brain areas activated when rats recalled the temporal order of object locations in a task, with either high or low levels of spatial interference. Animals showed spatiotemporal memory in both conditions once they spent more time exploring the older object locations relative to the more recent ones. We found no difference in the levels of c-Fos expression between high and low spatial interference. However, the levels of c-Fos expression in CA2 positively correlated with the discrimination index in the low spatial interference condition. More importantly, functional network connectivity analysis revealed a wider and more interconnected neuronal circuit in conditions of high than in low spatial interference. Our study advances the understanding of brain networks recruited in episodic memory with different degrees of spatial similarity.