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Current Biology : CB Sep 2023Remote memories play an important role in how we perceive the world, and they are rooted throughout the brain in "engrams": ensembles of cells that are formed during...
Remote memories play an important role in how we perceive the world, and they are rooted throughout the brain in "engrams": ensembles of cells that are formed during acquisition. Upon their reactivation, a specific memory can be recalled. Many studies have focused on the ensembles in CA1 of the hippocampus and the anterior cingulate cortex (ACC). However, the evolution of these components during systems' consolidation has not yet been comprehensively addressed. By applying transgenic approaches for ensemble identification, CLARITY, retro-AAV, and pseudo-rabies virus for circuit mapping, and chemogenetics for functional interrogation, we addressed the dynamics of recent and remote CA1 ensembles. We expected both stability (as they represent the same memory) and maturation (over time). Indeed, we found that CA1 engrams remain stable between recent and remote recalls, and the inhibition of engrams for recent recall during remote recall functionally impairs memory. We also found that new cells in the remote recall engram in the CA1 are not added randomly during maturation but differ according to their connections. First, we show in two ways that the anterograde CA1 → ACC engram cell projection grows larger. Finally, in the retrograde projections, the ACC reduces input to CA1 engram cells, whereas input from the entorhinal cortex and paraventricular nucleus of the thalamus increases. Our results shine fresh light on systems' consolidation by providing a deeper understanding of engram stability and maturation in the transition from recent to remote memory.
Topics: Hippocampus; Memory, Long-Term; Mental Recall; Entorhinal Cortex; Gyrus Cinguli
PubMed: 37586373
DOI: 10.1016/j.cub.2023.07.042 -
Advanced Science (Weinheim,... Aug 2023The hippocampal-entorhinal system supports cognitive function and is selectively vulnerable to Alzheimer's disease (AD). Little is known about global transcriptomic...
The hippocampal-entorhinal system supports cognitive function and is selectively vulnerable to Alzheimer's disease (AD). Little is known about global transcriptomic changes in the hippocampal-entorhinal subfields during AD. Herein, large-scale transcriptomic analysis is performed in five hippocampal-entorhinal subfields of postmortem brain tissues (262 unique samples). Differentially expressed genes are assessed across subfields and disease states, and integrated genotype data from an AD genome-wide association study. An integrative gene network analysis of bulk and single-nucleus RNA sequencing (snRNA-Seq) data identifies genes with causative roles in AD progression. Using a system-biology approach, pathology-specific expression patterns for cell types are demonstrated, notably upregulation of the A1-reactive astrocyte signature in the entorhinal cortex (EC) during AD. SnRNA-Seq data show that PSAP signaling is involved in alterations of cell- communications in the EC during AD. Further experiments validate the key role of PSAP in inducing astrogliosis and an A1-like reactive astrocyte phenotype. In summary, this study reveals subfield-, cell type-, and AD pathology-specific changes and demonstrates PSAP as a potential therapeutic target in AD.
Topics: Humans; Alzheimer Disease; Transcriptome; Genome-Wide Association Study; Hippocampus; Entorhinal Cortex
PubMed: 37232225
DOI: 10.1002/advs.202300876 -
Progress in Neuro-psychopharmacology &... Aug 2023Memories of everyday experiences involve the encoding of a rich and dynamic representation of present objects and their contextual features. Traditionally, the resulting... (Review)
Review
Memories of everyday experiences involve the encoding of a rich and dynamic representation of present objects and their contextual features. Traditionally, the resulting mnemonic trace is referred to as Episodic Memory, i.e. the "what", "where" and "when" of a lived episode. The journey for such memory trace encoding begins with the perceptual data of an experienced episode handled in sensory brain regions. The information is then streamed to cortical areas located in the ventral Medio Temporal Lobe, which produces multi-modal representations concerning either the objects (in the Perirhinal cortex) or the spatial and contextual features (in the parahippocampal region) of the episode. Then, this high-level data is gated through the Entorhinal Cortex and forwarded to the Hippocampal Formation, where all the pieces get bound together. Eventually, the resulting encoded neural pattern is relayed back to the Neocortex for a stable consolidation. This review will detail these different stages and provide a systematic overview of the major cortical streams toward the Hippocampus relevant for Episodic Memory encoding.
Topics: Memory, Episodic; Hippocampus; Entorhinal Cortex; Temporal Lobe; Neural Pathways
PubMed: 37086812
DOI: 10.1016/j.pnpbp.2023.110757 -
Frontiers in Neurology 2023Amnestic mild cognitive impairment (aMCI) is an early stage of Alzheimer's disease (AD). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF)...
BACKGROUND
Amnestic mild cognitive impairment (aMCI) is an early stage of Alzheimer's disease (AD). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) are employed to explore spontaneous brain function in patients with aMCI. This study applied ALFF and ReHo indicators to analyze the neural mechanism of aMCI by resting-state functional magnetic resonance imaging (rs-fMRI).
METHODS
Twenty-six patients with aMCI were included and assigned to the aMCI group. The other 26 healthy subjects were included as a healthy control (HC) group. Rs-fMRI was performed for all participants in both groups. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using DPARSF and SPM12 software based on MATLAB 2017a. Gender, age, and years of education were used as covariates to obtain ALFF and ReHo indices.
RESULTS
Compared with HC group, ALFF decreased in the left fusiform gyrus, left superior temporal gyrus, and increased in the left cerebellum 8, left inferior temporal gyrus, left superior frontal gyrus (BA11), and right inferior temporal gyrus (BA20) in the aMCI group ( < 0.05, FWE correction). In addition, ReHo decreased in the right middle temporal gyrus and right anterior cuneiform lobe, while it increased in the left middle temporal gyrus, left inferior temporal gyrus, cerebellar vermis, right parahippocampal gyrus, left caudate nucleus, right thalamus, and left superior frontal gyrus (BA6) ( < 0.05, FWE correction). In the aMCI group, the ALFF of the left superior frontal gyrus was negatively correlated with Montreal Cognitive Assessment (MoCA) score ( = -0.437, = 0.026), and the ALFF of the left superior temporal gyrus was positively correlated with the MoCA score ( = 0.550, = 0.004). The ReHo of the right hippocampus was negatively correlated with the Mini-Mental State Examination (MMSE) score ( = -0.434, = 0.027), and the ReHo of the right middle temporal gyrus was positively correlated with MMSE score ( = 0.392, = 0.048).
CONCLUSION
Functional changes in multiple brain regions rather than in a single brain region have been observed in patients with aMCI. The abnormal activity of multiple specific brain regions may be a manifestation of impaired central function in patients with aMCI.
PubMed: 37674874
DOI: 10.3389/fneur.2023.1244696 -
CNS Neuroscience & Therapeutics Feb 2024Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and... (Review)
Review
BACKGROUND AND OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a progressive motor and extra-motor neurodegenerative disease. This systematic review aimed to examine MRI biomarkers and neuropsychological assessments of the hippocampal and parahippocampal regions in patients with ALS.
METHODS
A systematic review was conducted in the Scopus and PubMed databases for studies published between January 2000 and July 2023. The inclusion criteria were (1) MRI studies to assess hippocampal and parahippocampal regions in ALS patients, and (2) studies reporting neuropsychological data in patients with ALS.
RESULTS
A total of 46 studies were included. Structural MRI revealed hippocampal atrophy, especially in ALS-FTD, involving specific subregions (CA1, dentate gyrus). Disease progression and genetic factors impacted atrophy patterns. Diffusion tensor imaging (DTI) showed increased mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and decreased fractional anisotropy (FA) in the hippocampal tracts and adjacent regions, indicating loss of neuronal and white matter integrity. Functional MRI (fMRI) revealed reduced functional connectivity (FC) between the hippocampus, parahippocampus, and other regions, suggesting disrupted networks. Perfusion MRI showed hypoperfusion in parahippocampal gyri. Magnetic resonance spectroscopy (MRS) found changes in the hippocampus, indicating neuronal loss. Neuropsychological tests showed associations between poorer memory and hippocampal atrophy or connectivity changes. CA1-2, dentate gyrus, and fimbria atrophy were correlated with worse memory.
CONCLUSIONS
The hippocampus and the connected regions are involved in ALS. Hippocampal atrophy disrupted connectivity and metabolite changes correlate with cognitive and functional decline. Specific subregions can be particularly affected. The hippocampus is a potential biomarker for disease monitoring and prognosis.
Topics: Humans; Diffusion Tensor Imaging; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Frontotemporal Dementia; Magnetic Resonance Imaging; Hippocampus; Biomarkers; Neuropsychological Tests; Atrophy
PubMed: 38334254
DOI: 10.1111/cns.14578 -
Human Brain Mapping Feb 2024The hippocampus and parahippocampal gyrus have been implicated as part of a tinnitus network by a number of studies. These structures are usually considered in the... (Review)
Review
The hippocampus and parahippocampal gyrus have been implicated as part of a tinnitus network by a number of studies. These structures are usually considered in the context of a "limbic system," a concept typically invoked to explain the emotional response to tinnitus. Despite this common framing, it is not apparent from current literature that this is necessarily the main functional role of these structures in persistent tinnitus. Here, we highlight a different role that encompasses their most commonly implicated functional position within the brain-that is, as a memory system. We consider tinnitus as an auditory object that is held in memory, which may be made persistent by associated activity from the hippocampus and parahippocampal gyrus. Evidence from animal and human studies implicating these structures in tinnitus is reviewed and used as an anchor for this hypothesis. We highlight the potential for the hippocampus/parahippocampal gyrus to facilitate maintenance of the memory of the tinnitus percept via communication with auditory cortex, rather than (or in addition to) mediating emotional responses to this percept.
Topics: Animals; Humans; Tinnitus; Hippocampus; Parahippocampal Gyrus; Limbic System; Auditory Cortex
PubMed: 38376166
DOI: 10.1002/hbm.26627 -
Nature Communications Oct 2023Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory...
Ketamine, a rapid-acting anesthetic and acute antidepressant, carries undesirable spatial cognition side effects including out-of-body experiences and spatial memory impairments. The neural substrates that underlie these alterations in spatial cognition however, remain incompletely understood. Here, we used electrophysiology and calcium imaging to examine ketamine's impacts on the medial entorhinal cortex and hippocampus, which contain neurons that encode an animal's spatial position, as mice navigated virtual reality and real world environments. Ketamine acutely increased firing rates, degraded cell-pair temporal firing-rate relationships, and altered oscillations, leading to longer-term remapping of spatial representations. In the reciprocally connected hippocampus, the activity of neurons that encode the position of the animal was suppressed after ketamine administration. Together, these findings demonstrate ketamine-induced dysfunction of the MEC-hippocampal circuit at the single cell, local-circuit population, and network levels, connecting previously demonstrated physiological effects of ketamine on spatial cognition to alterations in the spatial navigation circuit.
Topics: Mice; Animals; Ketamine; Entorhinal Cortex; Hippocampus; Neurons; Cognition
PubMed: 37805575
DOI: 10.1038/s41467-023-41750-4 -
Nature Jan 2024The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be...
The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience. Whereas location is known to be encoded by spatially tuned cell types in this brain region, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.
Topics: Animals; Mice; Entorhinal Cortex; Neurons; Parahippocampal Gyrus; Running; Time Factors; Darkness; Visual Cortex; Periodicity; Neural Pathways; Spatial Navigation; Memory, Episodic
PubMed: 38123682
DOI: 10.1038/s41586-023-06864-1 -
Frontiers in Neurology 2023Primary insomnia (PI) has a high global incidence, and effective treatments with fewer side effects are needed. Acupuncture, a treatment used in traditional Chinese...
IMPORTANCE
Primary insomnia (PI) has a high global incidence, and effective treatments with fewer side effects are needed. Acupuncture, a treatment used in traditional Chinese medicine, has become increasingly established as a treatment method for PI and is recognized by many physicians and patients. Some evidence has suggested that acupuncture was associated with improvements in objective sleep parameters and might induce changes in some brain regions. Individual studies with limited sample size and low detection thresholds may lead to false positives, and no systematic review of the effects of acupuncture has been conducted in PI.
OBJECTIVE
The aim of this systematic review and coordinate-based meta-analysis was to summarize the literature on fMRI evaluation of patients with PI treated with acupuncture.
DESIGN
We performed a methodical and comprehensive search of multiple publication databases (from inception to December 2022): Web of Science, PubMed, ScienceDirect, Embase, Wan Fang, China National Knowledge Infrastructure, and Chinese Scientific Journal Database. Bias and quality of studies were evaluated by three researchers. Furthermore, a seed-based D-mapping meta-analysis with permutation of subject images (SDM-PSI) was applied to investigate the central mechanisms behind acupuncture treatment at PI. The International Prospective Registry of Systematic Reviews received the protocol for this study. (PROSPERO: CRD42023400086).
RESULTS
The analysis included 305 patients with PI and 116 healthy controls from 11 studies. SDM-PSI analysis showed that patients with PI exhibited increased amplitudes of regional homogeneity and low-frequency fluctuations in the left superior frontal gyrus (1352 voxels, = 0.0028), right angular gyrus (14 voxels, = 0.0457), and cerebellum (12 voxels, = 0.0446). Acupuncture improved the function of right superior frontal gyrus (1, 404 voxels, = 0.0123), left inferior frontal gyrus (1068 voxels, = 0.0088), left inferior temporal gyrus (903 voxels, = 0.0074), left supramarginal gyrus (888 voxels, = 0.0113), left precuneus (457 voxels, = 0.0247), right precuneus (302 voxels, = 0.0191), left supplementary motor area (82 voxels, = 0.0354), and right parahippocampal gyrus (28 voxels, = 0.0379). The brain regions affected by non-acupoint acupuncture were all located in the frontal lobe. The Cochrane risk-of bias tool and MINORS5 were used for quality assessment and the included articles had high performance bias and attrition bias.
CONCLUSION
This coordinate-based meta-analysis found that acupuncture in patients with PI had significant effects on the default mode network, particularly on the frontal lobe and precuneus, and that non-acupoint acupuncture may provide some benefit to frontal brain region function.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO: CRD42023400086.
PubMed: 37533466
DOI: 10.3389/fneur.2023.1180393 -
Cell Reports Dec 2023The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory...
The hippocampus is broadly impacted by neuromodulations. However, how neuropeptides shape the function of the hippocampus and the related spatial learning and memory remains unclear. Here, we discover the crucial role of cholecystokinin (CCK) in heterosynaptic neuromodulation from the medial entorhinal cortex (MEC) to the hippocampus. Systematic knockout of the CCK gene impairs CA3-CA1 LTP and space-related performance. The MEC provides most of the CCK-positive neurons projecting to the hippocampal region, which potentiates CA3-CA1 long-term plasticity heterosynaptically in a frequency- and NMDA receptor (NMDAR)-dependent manner. Selective inhibition of MEC CCKergic neurons or downregulation of their CCK mRNA levels also impairs CA3-CA1 LTP formation and animals' performance in the water maze. This excitatory extrahippocampal projection releases CCK upon high-frequency excitation and is active during animal exploration. Our results reveal the critical role of entorhinal CCKergic projections in bridging intra- and extrahippocampal circuitry at electrophysiological and behavioral levels.
Topics: Cholecystokinin; Entorhinal Cortex; CA3 Region, Hippocampal; CA1 Region, Hippocampal; CA2 Region, Hippocampal; Synapses; Spatial Learning; Neuronal Plasticity; Animals; Mice; Mice, Knockout; Long-Term Potentiation
PubMed: 37979171
DOI: 10.1016/j.celrep.2023.113467