Hippocampus最新文献

Aging is associated with changes in spatial memory and navigation, yet the mechanisms underlying these changes are not yet fully understood. Environmental boundaries are among the most salient and reliable spatial cues, supporting both spatial memory and orientation. Here, we investigated how aging affects the use and the neural representation of boundary information during a virtual object location memory task. Healthy young and older adults navigated a square virtual environment while undergoing functional magnetic resonance imaging, allowing us to assess moment-to-moment encoding of distance to environmental boundaries in the entorhinal cortex and subiculum. Behaviorally, both age groups showed more accurate memory for objects located near boundaries, but this effect was amplified in older adults, whose spatial precision declined more steeply with increasing distance from boundaries. Older adults also exhibited a stronger bias to recall objects closer to boundaries. Analysis of navigation behavior revealed that older adults followed boundary-oriented paths regardless of target location, whereas young adults flexibly adapted their navigation based on spatial context. Neurally, older adults—but not young adults—showed significant blood-oxygen-level-dependent modulation by boundary distance in the entorhinal cortex and subiculum, with activity decreasing as participants moved farther from boundaries. This effect was most pronounced in low-performing older adults and was associated with stronger behavioral boundary bias, suggesting a maladaptive reliance on proximity-based cues. Together, our results provide converging behavioral and neural evidence that aging alters the use and representation of boundary information, with downstream effects on spatial memory. Altered boundary processing may represent a key mechanism contributing to age-related declines in spatial cognition.

Norepinephrine, acting through β-adrenergic receptors (β-ARs), has a key role in hippocampus-dependent forms of learning. Although β-AR activation also facilitates the induction of Hebbian LTP, recent findings indicate that a non-Hebbian form of synaptic plasticity, known as behavioral timescale synaptic plasticity (BTSP), underlies hippocampus-dependent spatial learning. To explore the role of noradrenergic signaling in BTSP, I investigated the effects of the β-AR activation on complex spike (CS) burst-dependent LTP, a form of BTSP induced by theta-pulse stimulation (TPS) protocols in the CA1 region of mouse hippocampal slices. β-AR activation not only enhanced the homosynaptic potentiation of synaptic transmission induced by TPS but also modulated heterosynaptic forms of plasticity critical for CS burst-dependent LTP induction. Specifically, β-AR activation enhanced the heterosynaptic facilitation of CS bursting induced by brief TPS trains and facilitated the ability of synapses to interact in a cooperative fashion to undergo LTP, even when independent groups of synapses were activated up to 10 s apart. β-AR activation also enhanced a CS burst-dependent form of heterosynaptic depression elicited by longer trains of TPS, resulting in a winner-take-all form of synaptic competition where the β-AR-mediated facilitation of LTP induction at one group of synapses was associated with a strong, heterosynaptic suppression of LTP at other synapses. Together, these findings indicate that β-AR activation dynamically regulates fundamental properties of CS burst-dependent synaptic plasticity by modulating multiple forms of heterosynaptic plasticity.

Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, poor quality MR images can lead to unreliable segmentation of MTL subregions. Considering that different MRI contrast mechanisms and field strengths (jointly referred to as “modalities” here) offer distinct advantages in imaging different parts of the MTL, we developed a multi-modality segmentation model using both 7T and 3T structural MRI to obtain robust segmentation in poor-quality images. MRI modalities including 3T T1-weighted, 3T T2-weighted, 7T T1-weighted and 7T T2-weighted (7T-T2w) of 197 participants were collected from a longitudinal aging study at the Penn Alzheimer's Disease Research Center. Among them, 7T-T2w was used as the primary modality, and all other modalities were rigidly registered to the 7T-T2w. A model derived from nnU-Net took these registered modalities as input and outputted subregion segmentation in 7T-T2w space. 7T-T2w images most of which had high quality from 25 selected training participants were manually segmented to train the multi-modality model. Modality augmentation, which randomly replaced certain modalities with Gaussian noise, was applied during training to guide the model to extract information from all modalities. The multi-modality model delivered good performance regardless of 7T-T2w quality, while the single-modality model under-segmented subregions in poor-quality images. The multi-modality model generally demonstrated stronger discrimination of A + MCI versus A-CU. Intra-class correlation and Bland–Altman plots demonstrate that the multi-modality model had higher longitudinal segmentation consistency in all subregions while the single-modality model had low consistency in poor-quality images. The multi-modality MRI segmentation model provides an improved biomarker for neurodegeneration in the MTL that is robust to image quality. It also provides a framework for other studies which may benefit from multimodal imaging.

Memory is a cornerstone of human behavior, and addiction offers a compelling model of its persistence and plasticity. The scope of engram research has rapidly expanded to include addiction-related phenomena. Addiction-related memories, like strong aversive memories, are often highly resistant to extinction and can continue to drive relapse long after drug use has ceased. These enduring behavioral effects suggest that drug engrams, sparsely distributed neural ensembles encoding drug-associated experiences, are stabilized by powerful synaptic and molecular plasticity. At the same time, their very malleability may hold the key to developing new treatments. This minireview synthesizes emerging findings on drug engrams, highlighting the specialized circuits, molecular mechanisms, and behavioral consequences tied to addiction-related memory traces. We focus on how engram tagging and reactivation techniques have revealed addiction-specific ensembles across several brain regions and important pathways that promote or attenuate drug-seeking behavior. We also discuss how direct manipulation of drug engrams may hold promise for weakening the influence of drug-associated cues and other relapse triggers, while enhancing protective circuits to reduce relapse risk. Still, fundamental questions remain such as how do drug engrams evolve during the transition from recreational use to addiction? Addressing these questions will be critical for developing circuit-informed, lasting interventions that target the memory systems sustaining addiction.

Neural activity and bodily functions are inherently rhythmic and related to each other. The occurrence of hippocampal sharp-wave ripples (SPW-Rs) and dentate spikes (DSs) supporting memory consolidation is regulated by the overall state of the brain, and they also seem to aggregate to a certain phase of the breathing cycle in naturally sleeping mice. Further, SPW-Rs and DSs synchronize to a variable degree between hemispheres, but how this is affected by the neural and bodily state is unclear. Here, we recorded dorsal hippocampal local-field potentials, electrocardiogram, and respiration for several hours under urethane anesthesia in adult male Sprague–Dawley rats. For a subset of rats, we injected atropine (50 mg/kg, i.p.) halfway into the recording to decrease cholinergic and parasympathetic tone. We found variable relation of hippocampal oscillations to breathing phase and none to the cardiac cycle phase. A decrease in breathing rate implying increased parasympathetic tone preceded the start of SPW-R bouts. Roughly 90% of DSs and half of SPW-Rs were unilateral. In most rats, SPW-Rs were more often bilateral during slow breathing compared to faster breathing. Atropine reduced the proportion of bilateral SPW-Rs. Both nonrapid eye movement sleep-like state and atropine increased the proportion of bilateral DSs under urethane anesthesia. Finally, in naturally sleeping rats, both DSs and SPW-Rs were bilateral ~60% of the time. In sum, urethane seems to desynchronize DSs but not SPW-Rs, and a low cholinergic and/or parasympathetic tone seems to dissociate SPW-Rs and to synchronize DSs in the two hippocampi. Whether these findings have relevance in terms of memory consolidation and behavior should be investigated in the future.

Our understanding of how the medial temporal lobe (MTL) contributes to human cognition has advanced enormously over the past half a century. My work in the 1990s characterizing the role of recollection and familiarity processes in episodic memory led me to study the MTL's role in these two memory processes. In the current paper, I provide a personal commentary in which I describe the motivating ideas, as well as the invaluable impact of mentors, colleagues, and students that led to a series of studies showing that conscious recollection is critically dependent on the hippocampus, whereas familiarity-based judgments are dependent on regions such as the perirhinal cortex.