Hippocampus最新文献

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.

Grid and place cells typically fire at progressively earlier phases within each cycle of the theta rhythm as rodents run across their firing fields, a phenomenon known as theta phase precession. Here, we report theta phase precession relative to turning angle in theta-modulated head direction cells within the anteroventral thalamic nucleus (AVN). As rodents turn their heads, these cells fire at progressively earlier phases as head direction sweeps over their preferred tuning direction. The degree of phase precession increases with angular head velocity. Moreover, phase precession is more pronounced in those theta-modulated head direction cells that exhibit theta skipping, with a stronger theta-skipping effect correlating with a higher degree of phase precession. These findings are consistent with a ring attractor model that integrates external theta input with internal firing rate adaptation—a phenomenon we identified in head direction cells within AVN. Our results broaden the range of information known to be subject to neural phase coding and enrich our understanding of the neural dynamics supporting spatial orientation and navigation.

Long-term potentiation (LTP) is proposed to be the molecular mechanism underlying learning and memory in the brain. A key event for LTP is the influx of calcium into post-synaptic neurons via multiple ion channel control systems. One such system involves N-methyl-D-aspartate receptors (NMDARs), which were originally believed to be essential for LTP and new learning. Recent studies have demonstrated that hippocampal NMDARs are critical for learning new spatial information in a novel environment; however, when pre-training occurs prior to new spatial learning, these receptors are not needed. Additionally, researchers have shown that activation of voltage-gated calcium channels (VGCCs) and their associated calcium influx can induce LTP independent of NMDARs. These findings led to the idea that the amount of calcium required for learning in hippocampus depends on whether the new learning takes place in a novel or familiar environment, with a novel environment demanding greater calcium influx. It was hypothesized that to impair new learning in a familiar environment both NMDARs and VGCCs would need to be blocked. Long-Evans rats were trained in a three-phase version of the Morris water task, which included pre-training, new learning mass-training, and a probe test. Prior to mass-training, intrahippocampal VGCCs were blocked individually or in combination with NMDARs blockade to evaluate their effects on the rats learning and memory. The results showed that blocking both NMDARs and VGCCs simultaneously impaired new spatial learning with familiar information, whereas VGCC blockade alone did not.

The cover image is based on the article The Suprapyramidal and Infrapyramidal Blades of the Dentate Gyrus Exhibit Different GluN Subunit Content and Dissimilar Frequency-Dependent Synaptic Plasticity In Vivo by Christina Strauch et al., https://doi.org/10.1002/hipo.70002.

The entorhinal cortex sends afferent information to the hippocampus by means of the perforant path (PP). The PP input to the dentate gyrus (DG) terminates in the suprapyramidal (sDG) and infrapyramidal (iDG) blades. Different electrophysiological stimulation patterns of the PP can generate hippocampal synaptic plasticity. Whether frequency-dependent synaptic plasticity differs in the sDG and iDG is unclear. Here, we compared medial PP–DG responses in freely behaving adult rats and found that synaptic plasticity in the sDG is broadly frequency dependent, whereby long-term depression (LTD, > 24 h) is induced with stimulation at 1 Hz, short-term depression (< 2 h) is triggered by 5 or 10 Hz, and long-term potentiation (LTP) of increasing magnitudes is induced by 200 and 400 Hz stimulation, respectively. By contrast, although the iDG expresses STD following 5 or 10 Hz stimulation, LTD induced by 1 Hz is weaker, LTP is not induced by 200 Hz and LTP induced by 400 Hz stimulation is significantly smaller in magnitude than LTP induced in sDG. Furthermore, the stimulus–response relationship of iDG is suppressed compared to sDG. These differences may arise from differences in granule cell properties, or the complement of NMDA receptors. Patch clamp recordings, in vitro, revealed reduced firing frequencies in response to high currents, and different action potential thresholds in iDG compared to sDG. Assessment of the expression of GluN subunits revealed significantly lower expression levels of GluN1, GluN2A, and GluN2B in the middle molecular layer of iDG compared to sDG. Taken together, these data indicate that synaptic plasticity in the iDG is weaker, less persistent and less responsive to afferent frequencies than synaptic plasticity in sDG. Effects may be mediated by weaker NMDA receptor expression and differences in neuronal responses in iDG versus sDG. These characteristics may explain reported differences in experience-dependent information processing in the suprapyramidal and infrapyramidal blades of the DG.