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Pathological changes, such as microglia activation in the hippocampus frequently occur in individuals with animal models of depression; however, they may share a common cellular mechanism, such as endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Mitochondria associated membranes (MAMs) are communication platforms between ER and mitochondria. This study aimed to investigate the role of intracellular stress responses, especially structural and functional changes of MAMs in depression. We used chronic social defeat stress (CSDS) to mimic depression in C57 mice to investigate the pathophysiological changes in the hippocampus associated with depression and assess the antidepressant effect of electroacupuncture (EA). Molecular, histological, and electron microscopic techniques were utilized to study intracellular stress responses, including the ER stress pathway reaction, mitochondrial damage, and structural and functional changes in MAMs in the hippocampus after CSDS. Proteomics technology was employed to explore protein-level changes in MAMs caused by CSDS. CSDS caused mitochondrial dysfunction, ER stress, closer contact between ER and mitochondria, and enrichment of functional protein clusters at MAMs in hippocampus along with depressive-like behaviors. Also, EA showed beneficial effects on intracellular stress responses and depressive-like behaviors in CSDS mice. The cellular specificity of MAMs related protein changes in CSDS mice was not explored. In the hippocampus, ER stress and mitochondrial damage occur, along with enriched mitochondria-ER interactions and MAM-related protein enrichment, which may contribute to depression's pathophysiology. EA may improve depression by regulating intracellular stress responses. [Display omitted] • CSDS causes mitochondrial dysfunction, ER stress, and MAM protein enrichment along with depression-like behaviors. • An ER stress inhibitor and a mitochondrial protective agent improve depressive-like behaviors. • EA has antidepressant effects and can improve the structural and functional changes in MAMs caused by CSDS. [ABSTRACT FROM AUTHOR]

• Neural mechanism of object encoding in MTL revealed by human intracranial EEGs. • PRC showed strongest broad-gamma activation ∼100 ms in response to object stimuli. • Found strong bidirectional low-frequency interactions of PRC with PHC and HPC. • Findings support the PRC-HPC-ventral object pathway. The perirhinal cortex (PRC) and parahippocampal cortex (PHC) are core regions along the visual dual-stream. The specific functional roles of the PRC and PHC and their interactions with the downstream hippocampus cortex (HPC) are crucial for understanding visual memory. Our research used human intracranial EEGs to study the neural mechanism of the PRC, PHC, and HPC in visual object encoding. Single-regional function analyses found evidence that the PRC, PHC, and HPC are activated ∼100 ms within the broad-gamma band and that the PRC was more strongly activated than either the PHC or the HPC after an object stimulus. Inter-regional analyses showed strong bidirectional interactions of the PRC with both the PHC and HPC in the low-frequency band, whereas the interactions between the PHC and HPC were not significant. These findings demonstrated the core role of the PRC in encoding visual object information and supported the hypothesis of PRC-HPC-ventral object pathway. The recruitment of the PHC and its interaction with the PRC in visual object encoding also provide new insights beyond the traditional dorsal-stream hypothesis. [ABSTRACT FROM AUTHOR]

New memories are integrated into prior knowledge of the world. But what if consecutive memories exert opposing demands on the host brain network? We report that acquiring a robust (food-context) memory constrains the mouse hippocampus within a population activity space of highly correlated spike trains that prevents subsequent computation of a flexible (object-location) memory. This densely correlated firing structure developed over repeated mnemonic experience, gradually coupling neurons in the superficial sublayer of the CA1 stratum pyramidale to whole-population activity. Applying hippocampal theta-driven closed-loop optogenetic suppression to mitigate this neuronal recruitment during (food-context) memory formation relaxed the topological constraint on hippocampal coactivity and restored subsequent flexible (object-location) memory. These findings uncover an organizational principle for the peer-to-peer coactivity structure of the hippocampal cell population to meet memory demands. [ABSTRACT FROM AUTHOR]

The therapeutic potential of suppressing polypyrimidine tract-binding protein 1 (Ptbp1) messenger RNA by viral transduction in a post-stroke dementia mouse model has not yet been examined. In this study, 3 days after cerebral ischemia, we injected a viral vector cocktail containing adeno-associated virus (AAV)-pGFAP-mCherry and AAV-pGFAP-CasRx (control vector) or a cocktail of AAV-pGFAP-mCherry and AAV-pGFAP-CasRx-SgRNA-(Ptbp1) (1:5, 1.0 × 1011 viral genomes) into post-stroke mice via the tail vein. We observed new mCherry/NeuN double-positive neuron-like cells in the hippocampus 56 days after cerebral ischemia. A portion of mCherry/GFAP double-positive astrocyte-like glia could have been converted into new mCherry/NeuN double-positive neuron-like cells with morphological changes. The new neuronal cells integrated into the dentate gyrus and recognition memory was significantly ameliorated. These results demonstrated that the in vivo conversion of hippocampal astrocyte-like glia into functional new neurons by the suppression of Ptbp1 might be a therapeutic strategy for post-stroke dementia. [ABSTRACT FROM AUTHOR]

Introduction: Glyphosate-based herbicides (GBHs) have been shown to have significant neurotoxic effects, affecting both the structure and function of the brain, and potentially contributing to the development of neurodegenerative disorders. Despite the known importance of glycosylation in disease progression, the glycome profile of systems exposed to GBH has not been thoroughly investigated. Methods: In this study, we conducted a comprehensive glycomic profiling using LC-MS/MS, on the hippocampus and prefrontal cortex (PFC) of juvenile rats exposed to GBH orally, aiming to identify glyco-signature aberrations after herbicide exposure. Results: We observed changes in the glycome profile, particularly in fucosylated, high mannose, and sialofucosylated N-glycans, which may be triggered by GBH exposure. Moreover, we found major significant differences in the N-glycan profiles between the GBH-exposed group and the control group when analyzing each gender independently, in contrast to the analysis that included both genders. Notably, gender differences in the behavioral test of object recognition showed a decreased performance in female animals exposed to GBH compared to controls (p < 0.05), while normal behavior was recorded in GBH-exposed male rats (p > 0.05). Conclusion: These findings suggest that glycans may play a role in the neurotoxic effect caused by GBH. The result suggests that gender variation may influence the response to GBH exposure, with potential implications for disease progression and specifically the neurotoxic effects of GBHs. Understanding these gender-specific responses could enhance knowledge of the mechanisms underlying GBH-induced toxicity and its impact on brain health. Overall, our study represents the first detailed analysis of N-glycome profiles in the hippocampus and PFC of rats chronically exposed to GBH. The observed alterations in the expression of N-glycan structures suggest a potential neurotoxic effect associated with chronic GBH exposure, highlighting the importance of further research in this area. [ABSTRACT FROM AUTHOR]

In layer II of the entorhinal cortex, the principal neurons that project to the dentate gyrus and the CA3/2 hippocampal fields markedly express the large glycoprotein reelin (Re + ECLII neurons). In rodents, neurons located at the dorsal extreme of the EC, which border the rhinal fissure, express the highest levels, and the expression gradually decreases at levels successively further away from the rhinal fissure. Here, we test two predictions deducible from the hypothesis that reelin expression is strongly correlated with neuronal metabolic rate. Since the mitochondrial turnover rate serves as a proxy for energy expenditure, the mitophagy rate arguably also qualifies as such. Because messenger RNA of the canonical promitophagic BCL2 and adenovirus E1B 19-kDa-interacting protein 3 (Bnip3) is known to be highly expressed in the EC, we predicted that Bnip3 would be upregulated in Re + ECLII neurons, and that the degree of upregulation would strongly correlate with the expression level of reelin in these neurons. We confirm both predictions, supporting that the energy requirement of Re + ECLII neurons is generally high and that there is a systematic increase in metabolic rate as one moves successively closer to the rhinal fissure. Intriguingly, the systematic variation in energy requirement of the neurons that manifest the observed reelin gradient appears to be consonant with the level of spatial and temporal detail by which they encode information about the external environment. [ABSTRACT FROM AUTHOR]

Estrogens are believed to modulate cognitive functions in part through the modulation of synaptic transmission in the cortex and hippocampus. Administration of 17β‐estradiol (E2) can rapidly enhance excitatory synaptic transmission in the hippocampus and facilitate excitatory synaptic transmission in rat lateral entorhinal cortex via activation of the G protein‐coupled estrogen receptor‐1 (GPER1). To assess the mechanisms through which GPER1 activation facilitates synaptic transmission, we assessed the effects of acute 10 nM E2 administration on pharmacologically isolated evoked excitatory and inhibitory synaptic currents in layer II/III entorhinal neurons. Female Long‐Evans rats were ovariectomized between postnatal day (PD) 63 and 74 and implanted with a subdermal E2 capsule to maintain continuous low levels of E2. Electrophysiological recordings were obtained between 7 and 20 days after ovariectomy. Application of E2 for 20 min did not significantly affect AMPA or NMDA receptor‐mediated excitatory synaptic currents. However, GABA receptor‐mediated inhibitory synaptic currents (IPSCs) were markedly reduced by E2 and returned towards baseline levels during the 20‐min washout period. The inhibition of GABA‐mediated IPSCs was blocked in the presence of the GPER1 receptor antagonist G15. GPER1 can modulate protein kinase A (PKA), but blocking PKA with intracellular KT5720 did not prevent the E2‐induced reduction in IPSCs. GPER1 can also stimulate extracellular signal‐regulated kinase (ERK), a negative modulator of GABAA receptors, and blocking activation of ERK with PD90859 prevented the E2‐induced reduction of IPSCs. E2 can therefore result in a rapid GPER1 and ERK signaling‐mediated reduction in GABA‐mediated IPSCs. This provides a novel mechanism through which E2 can rapidly modulate synaptic excitability in entorhinal layer II/III neurons and may also contribute to E2 and ERK‐dependent alterations in synaptic transmission in other brain areas. [ABSTRACT FROM AUTHOR]

Hippocampal area CA2 has garnered attention in recent times owing to its significant involvement in social memory and distinctive plasticity characteristics. Research has revealed that the CA2 region demonstrates a remarkable resistance to plasticity, particularly in the Schaffer Collateral (SC)‐CA2 pathway. In this study we investigated the role of Nogo‐A, a well‐known axon growth inhibitor and more recently discovered plasticity regulator, in modulating plasticity within the CA2 region. The findings demonstrate that blocking Nogo‐A in male rat hippocampal slices facilitates the establishment of both short‐term and long‐term plasticity in the SC‐CA2 pathway, while having no impact on the Entorhinal Cortical (EC)‐CA2 pathway. Additionally, the study reveals that inhibiting Nogo‐A enables association between the SC and EC pathways. Mechanistically, we confirm that Nogo‐A operates through its well‐known co‐receptor, p75 neurotrophin receptor (p75NTR), and its downstream signaling factor such as Rho‐associated protein kinase (ROCK), as their inhibition also allows plasticity induction in the SC‐CA2 pathway. Additionally, the induction of long‐term depression (LTD) in both the EC and SC‐CA2 pathways led to persistent LTD, which was not affected by Nogo‐A inhibition. Our study demonstrates the involvement of Nogo‐A mediated signaling mechanisms in limiting synaptic plasticity within the CA2 region. [ABSTRACT FROM AUTHOR]

Introduction/Purpose: As individuals age, the entorhinal cortex (ERC) and hippocampus--crucial structures for memory--tend to atrophy, with related cognitive decline. Simultaneously, lifestyle factors that can be modified, such as exercise and sleep, have been separately linked to slowing of brain atrophy and functional decline. However, the synergistic impact of fitness and sleep on susceptible brain structures in aging adults remains uncertain. Methods: We examined both independent and interactive associations of fitness and subjective sleep quality with regard to ERC thickness and hippocampal volume in 598middle-aged and older adults from the Human Connectome Lifespan Aging Project. Cardiorespiratory fitness was assessed using the 2-min walk test, whereas subjective sleep quality was measured with the continuous Pittsburgh Sleep Quality Index global score. High-resolution structural magnetic resonance imaging was used to examine mean ERC thickness and bilateral hippocampal volume. Through multiple linear regression analyses, we investigated the moderating effects of subjective sleep quality on the association between fitness and brain structure, accounting for age, sex, education, body mass index, gait speed, and subjective physical activity. Results: We found that greater cardiorespiratory fitness, but not subjective sleep quality, was positively associated with bilateral hippocampal volume and ERC thickness. Notably, significant interaction effects suggest that poor subjective sleep quality was associated with a weaker association between fitness and both hippocampal volume and ERC thickness. Conclusions: Findings suggest the potential importance of both cardiorespiratory fitness and subjective sleep quality in preserving critical, age-vulnerable brain structures. Interventions targeting brain health should consider potential combined effects of sleep and fitness on brain health. [ABSTRACT FROM AUTHOR]

Background Multiple hippocampal transection (MHT) is a surgical technique used for the treatment of drug-resistant mesial temporal lobe epilepsy in situations where standard procedures would pose a high risk for memory deterioration. During MHT, the longitudinal fibers of the hippocampus, implicated in epilepsy spreading, are interrupted, while the transverse memory circuits are spared. The extent of MHT is governed by intraoperative electrocorticography; abolition of epileptic discharges serves as an end point to terminate the transection. In other words, the aim of MHT is not the anatomical completeness of hippocampal transection. In contrast, we hypothesize that only the complete transection of hippocampal cross-section is needed to durably terminate epilepsy, avoiding possible postoperative reorganization of longitudinal pathways. Here, we report an anatomical study designed to evaluate the feasibility of complete transection of hippocampus with the aid of ultrasound neuronavigation and we propose new instruments to reach this goal. Methods Five cadaveric brains were analyzed in this study. MHT was performed on both sides of each brain either with or without ultrasound neuronavigation. The percentage of transected cross-section of the hippocampus was measured using magnetic resonance imaging (MRI) and both sides were compared. Results The ultrasound-guided MHTs were more likely to achieve complete hippocampal transection compared with the nonnavigated MHT transection (73 vs 58%; p < 0.01). Our study also allowed us to propose specialized transectors to minimize invasivity of this procedure. Conclusion Completeness of MHT can be better reached with the aid of an ultrasound neuronavigation system; modified instruments for this procedure were also designed. [ABSTRACT FROM AUTHOR]

Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats. Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats. [ABSTRACT FROM AUTHOR]

Background: Computerized cognitive training (CCT) has been proposed as a potential therapy for cognitive decline. One of the benefits of CCT is a transfer effect, but its mechanism on the memory domain is unclear. This study aimed to investigate the transfer effect of non‐memory multidomain CCT on the memory domain and its neural basis in patients with mild cognitive impairment (MCI) through a randomized controlled trial. Methods: Patients with MCI recruited from memory clinics were randomly assigned to either the CCT or the control group. The CCT group received multidomain CCT training excluding memory training, while the control group read educational books with learning‐based quizzes twice a week for 8 weeks. Participants underwent memory tests yielding a composite score, other cognitive domain tests, non‐cognitive scales, and resting‐state functional magnetic resonance imaging (rsfMRI), at baseline and after intervention. Within‐ and between‐group comparisons, group × time interactions, and seed‐to‐voxel analyses in memory‐involving brain networks were performed. Results: The CCT group showed improvement over the control group in memory domain (Group × time, F = 5.87, P = 0.03, η2 = 0.31), which was related with the increased connectivity in the hippocampal‐frontal and fusiform‐occipital network. No other cognitive and non‐cognitive symptoms differed between groups after adjusting for covariates. Conclusion: Eight weeks of multidomain CCT without memory training improved memory function and restored functional network in the hippocampal and medial temporal region in MCI patients. These results can provide evidence for the transferring ability of CCT on memory functioning with its neural basis. [ABSTRACT FROM AUTHOR]

Objective(s): Prenatal stress (PS) can adversely affect cognitive and psychological functions in the offspring. This study aimed to determine the effect of PS and extremely low-frequency electromagnetic field (ELF-EMF) on spatial memory, serum corticosterone, brain-derived neurotrophic factor (BDNF) concentrations, and hippocampal BDNF levels in adult male offspring. Materials and Methods: Female Wistar rats were randomly divided into four groups (n=6): Control, Stress, ELF-EMF (exposure to ELF-EMF), and S+EMF (simultaneous exposure to stress and the ELFEMF) groups. Animals received interventions for 21 days before and 21 days during pregnancy (a total of 42 days). On the offspring’s 90th postnatal day (PND), spatial memory was tested using Morris Water Maze, serum Corticosterone and BDNF levels were measured by the ELISA method, and hippocampal BDNF levels were measured by Western blotting. Results: PS did not affect spatial memory in the adult male offspring; however, it significantly (P<0.05) increased se-rum corticosterone levels compared to the control and EMF groups. Simultaneous induction of stress with ELF-EMF disrupted the memory acquisition phase. Serum and hippocampal BDNF levels increased significantly (P<0.05) in the EMF group compared to the stress group. Conclusion: Based on our findings, PS can increase serum corticosterone levels without affecting spatial memory. However, induction of ELF-EMF with stress has a destructive effect on spatial memory with no change in the corticosterone levels. Compared to stress, prenatal exposure to ELF-EMF increases serum and hippocampal BDNF levels. Further studies are needed to determine the underlying mechanisms of these findings. [ABSTRACT FROM AUTHOR]

The article focuses on defining clinical criteria for identifying limbic-predominant amnestic neurodegenerative syndrome (LANS) in older patients and the use of imaging and clinical features to differentiate LANS from Alzheimer's disease.

Chronic stress is a universal condition commonly associated with many psychiatric diseases. An extensive body of evidence discussed hippocampal affection upon chronic stress exposure, however, the underlying molecular pathways still need to be identified. We investigated the impact of chronic stress on miR200/BMP/Olig‐2 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig‐2 positive cells count in hippocampi of chronic stress‐exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig‐2 proteins. This work underscores the amelioration of the stress‐induced behavioral changes, inhibition of miR200/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination. [ABSTRACT FROM AUTHOR]

A quiz concerning a notable scientist honored by a tickborne protozoan infection focuses on Victor Babeș (1854–1926), who made significant contributions to pathology and microbiology, including his pioneering work in rabies vaccine development.

Hippocampal volume (HV) is sensitive to environmental influences. Under normative conditions in humans, HV increases linearly into childhood and asymptotes in early adulthood. Studies of humans and nonhuman animals have provided evidence of inverse relationships between several measures of stress and HV. Using structural equation modeling, this study aimed to characterize the relationships of age, basal cortisol, biological sex, and lifetime perceived stress with bilateral HV in a sample of healthy adolescents and adolescents at clinical high risk for psychosis (CHR-P) (N = 571, 43% female; age range = 12–19.9 years). This sample included 469 individuals at CHR-P and 102 healthy comparison participants from the combined baseline cohorts of the second and third NAPLS (North American Prodrome Longitudinal Study). A structural model that constrained the individual effects of basal cortisol and perceived stress to single path coefficients, and freely estimated the effects of age and biological sex in group models, optimized model fit and parsimony relative to other candidate models. Significant inverse relationships between basal cortisol and bilateral HV were observed in adolescents at CHR-P and healthy comparison participants. Significant sex differences in bilateral HV were also observed, with females demonstrating smaller HV than males in both groups. Multigroup structural equation modeling revealed heterogeneity in the relationships of age and biological sex with basal cortisol, lifetime perceived stress, and bilateral HV in individuals at CHR-P and healthy comparison participants. Moreover, the findings support previous literature indicating that elevated basal cortisol is a nonspecific risk factor for reduced HV. [ABSTRACT FROM AUTHOR]

Prediction errors (PEs) function as learning signals. It is yet unclear how varying compared to repetitive PEs affect episodic memory in brain and behavior. The current study investigated cerebral and behavioral effects of experiencing either multiple alternative versions ("varying") or one single alternative version ("repetitive") of a previously encoded episode. Participants encoded a set of episodes ("originals") by watching videos showing toy stories. During scanning, participants either experienced originals, one single, or multiple alternative versions of the previously encoded episodes. Participants' memory performance was tested through recall of original objects. Varying and repetitive PEs revealed typical brain responses to the detection of mismatching information including inferior frontal and posterior parietal regions, as well as hippocampus, which is further linked to memory reactivation, and the amygdala, known for modulating memory consolidation. Furthermore, experiencing varying and repetitive PEs triggered distinct brain areas as revealed by direct contrast. Among others, experiencing varying versions triggered activity in the caudate, a region that has been associated with PEs. In contrast, repetitive PEs activated brain areas that resembled more those for retrieval of originally encoded episodes. Thus, ACC and posterior cingulate cortex activation seemed to serve both reactivating old and integrating new but similar information in episodic memory. Consistent with neural findings, participants recalled original objects less accurately when only presented with the same, but not varying, PE during fMRI. The current findings suggest that repeated PEs interact more strongly with a recalled original episodic memory than varying PEs. [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter required for excitation/inhibition balance is synthesized by the glutamic acid decarboxylases (GADs) in GABAergic neurons. The levels and activity of GADs are strongly correlated with GABA and neural transmission. Dysregulation of GADs and GABA is associated with various neurological disorders. The study used psoralidin, found in the seeds of Psoralea corylifolia, to investigate its effect on GAD levels and regulatory mechanisms in primary cortical neurons. Psoralidin reduced GAD67 through transcriptional regulation. The reduction was not mediated by the N-methyl-D-aspartate receptor. Additionally, psoralidin attenuated the formation of inhibitory synapses in primary hippocampal neurons. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of high‐intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. Materials and Methods: Forty‐eight Wistar rats were divided into four groups: non‐trained (NT); non‐trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. Results: PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p <.05), while HIIT attenuated these changes (p <.05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]‐α, interleukin [IL]‐10, TNF‐α/IL‐10 and IL‐1β/IL‐10 ratios, p <.05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p <.05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p <.05). Conclusions: HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD. [ABSTRACT FROM AUTHOR]

Pediatric posterior fossa tumor (PFT) survivors experience long-term cognitive sequelae, including memory disorders, for which irradiation is one of the main risk factors. The aims of the present study were to (1) explore the profile of impairment in episodic, semantic, working and procedural memory systems in irradiated versus nonirradiated PFT survivors, and (2) test whether an autobiographical questionnaire and a two-phase ecological test (Epireal) assessing episodic memory are more sensitive to radiation-induced hippocampal damage than commonly used tests. A total of 60 participants (22 irradiated PFT survivors, 17 nonirradiated PFT survivors, and 21 controls) were included in the prospective IMPALA study. They all underwent a broad battery of tests assessing the different memory systems in two 2-day sessions 3 weeks apart. We performed between-groups comparisons and analyzed impairment profiles, using -1.65 SD s as a cut-off. For irradiated patients, correlations were calculated between mean radiation doses to key brain structures involved in memory (hippocampus, cerebellum, and striatum) and corresponding memory scores. PBT survivors performed significantly more poorly than controls (p < 0.001) on conventional tests of episodic, semantic and working memory: 64% of irradiated patients and 35% of nonirradiated patients had a deficit in at least two memory systems, with episodic memory impairment being more specific to the irradiated group. Epireal had a larger effect size than the other episodic memory tests, allowing us to detect deficits in a further 18% of irradiated patients. These deficits were correlated with the mean radiation dose to the left hippocampus. Memory impairment is a frequent long-term cognitive sequela in PFT survivors, especially after radiation therapy. New ecological tests of episodic memory that are more sensitive to radiation-induced deficits than conventional tests could yield specific markers of the toxicity of medial temporal lobe irradiation. • 86% of irradiated patients had a deficit in at least one memory system. • 65% of nonirradiated patients had a deficit in at least one memory system. • Episodic memory was specifically impaired in irradiated patients. • Episodic tests were more sensitive to radiation toxicity on the left hippocampus. [ABSTRACT FROM AUTHOR]

Studies have confirmed that anxiety, especially worry and rumination, are associated with increased risk for cognitive decline, including Alzheimer's disease and related dementias (ADRD). Hippocampal atrophy is a hallmark of ADRD. We investigated the association between hippocampus and its subfield volumes and late-life global anxiety, worry, and rumination, and emotion regulation strategies. We recruited 110 participants with varying worry severity who underwent magnetic resonance imaging and clinical interviews. We conducted cross-sectional regression analysis between each subfield and anxiety, worry, rumination, reappraisal, and suppression while adjusting for age, sex, race, education, cumulative illness burden, stress, neuroticism, and intracranial volume. We imputed missing data and corrected for multiple comparisons across regions. Greater worry was associated with smaller subiculum volume, whereas greater use of reappraisal was associated with larger subiculum and CA1 volume. Greater worry may be detrimental to the hippocampus and to subfields involved in early ADRD pathology. Use of reappraisal appears protective of hippocampal structure. Worry and reappraisal may be modifiable targets for ADRD prevention. • How is late-life anxiety and its phenotypes associated with hippocampal subfields? • We found that severe worry was associated with smaller subiculum volumes. • We additionally found that reappraisal was associated with larger subfield volumes. • Worry and reappraisal may be modifiable targets for Alzheimer's prevention. [ABSTRACT FROM AUTHOR]

Age-related episodic memory decline is attributed to functional alternations in the hippocampus. Less clear is how aging affects the functional connections of the hippocampus to the rest of the brain during episodic memory processing. We examined fMRI data from the CamCAN dataset, in which a large cohort of participants watched a movie (N = 643; 18–88 years), a proxy for naturalistic episodic memory encoding. We examined connectivity profiles across the lifespan both within the hippocampus (anterior, posterior), and between the hippocampal subregions and cortical networks. Aging was associated with reductions in contralateral (left, right) but not ipsilateral (anterior, posterior) hippocampal subregion connectivity. Aging was primarily associated with increased coupling between the anterior hippocampus and regions affiliated with Control, Dorsal Attention and Default Mode networks, yet decreased coupling between the posterior hippocampus and a selection of these regions. Differences in age-related hippocampal-cortical, but not within-hippocampus circuitry selectively predicted worse memory performance. Our findings comprehensively characterize hippocampal functional topography in relation to cognition in older age, suggesting that shifts in cortico-hippocampal connectivity may be sensitive markers of age-related episodic memory decline. • Aging alters functional specialization of hippocampal subregions. • Contralateral, not ipsilateral subregion connectivity decreases. • Connectivity patterns shift from posterior to anterior regions. • Cortical, not within subregion connectivity differences predict worse episodic memory. [ABSTRACT FROM AUTHOR]

This study provides a concise and structured overview of a dosimetric comparison study conducted to assess the feasibility and effectiveness of 4 advanced radiotherapy techniques in treating brain metastases with hippocampus sparing and simultaneous integrated boost (HS-WBRT+SIB). Eleven patients with brain metastases previously treated with radiotherapy were included in the study. Planning CT scans with 2 mm slice thickness and MR imaging were used for contouring and dose prescription. The bilateral hippocampus and other organs at risk (OARs) were automatically contoured, and hippocampal avoidance regions (HAR) were defined as a 7 mm 3D expansion around the hippocampus. Gross tumor volume for each metastasis (GTV met) and planning target volume for metastases (PTV met) were delineated. The whole-brain CTV (CTV WB) and planning target volume for whole brain (PTV WB) were defined accordingly. Treatment planning and optimization were conducted using state-of-the-art radiotherapy techniques: Ethos, HyperArc, VMAT, and Tomotherapy. Tomotherapy achieved the highest D98% for PTV met , indicating the best metastasis coverage. HyperArc plans showed the highest D98% for PTV WB , suggesting superior whole-brain coverage. Tomotherapy demonstrated significantly lower D98%, D2%, and D mean values for the hippocampus, indicating its superiority in sparing the hippocampus. VMAT resulted in the lowest D2% values for the eyes, optic nerves, brainstem, and hypophysis, showing the best sparing of these critical structures. Tomotherapy consistently achieved lower D mean values for parotids, oral cavity, and lips compared to the other techniques. The dosimetric comparison revealed distinct strengths and weaknesses for each radiotherapy technique. Tomotherapy excelled in sparing the hippocampus, while VMAT showed promise in sparing OARs. HyperArc plans demonstrated the best overall whole-brain coverage. These findings should guide clinicians in selecting the most suitable technique based on patient characteristics and institutional resources. [ABSTRACT FROM AUTHOR]

Narratives fundamentally shape the way we remember real-life experiences. However, neuroscientists have only begun to understand how narratives impact the way our brains support memory. In this opinion piece, I illustrate how the hippocampus, a key region of the brain for memory, transforms our experiences into larger narratives in memory. Furthermore, I argue that the hippocampus provides a biological basis for "intertextuality" -- that is, all experiences or texts may be necessarily understood and remembered in relation to other experiences or texts. An intertextual hippocampus has tangible consequences for our lives and our art. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Schizophrenia (SCZ) and anorexia nervosa (AN) are 2 severe and highly heterogeneous disorders showing substantial familial co-aggregation. Genetic factors play a significant role in both disorders, but the shared genetic etiology between them is yet to be investigated. Study Design Using summary statistics from recent large genome-wide association studies on SCZ (N cases = 53 386) and AN (N cases = 16 992), a 2-sample Mendelian randomization analysis was conducted to explore the causal relationship between SCZ and AN. MiXeR was employed to quantify their polygenic overlap. A conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was adopted to identify loci jointly associated with both disorders. Functional annotation and enrichment analyses were performed on the shared loci. Study Results We observed a cross-trait genetic enrichment, a suggestive bidirectional causal relationship, and a considerable polygenic overlap (Dice coefficient = 62.2%) between SCZ and AN. The proportion of variants with concordant effect directions among all shared variants was 69.9%. Leveraging overlapping genetic associations, we identified 6 novel loci for AN and 33 novel loci for SCZ at condFDR <0.01. At conjFDR <0.05, we identified 10 loci jointly associated with both disorders, implicating multiple genes highly expressed in the cerebellum and pituitary and involved in synapse organization. Particularly, high expression of the shared genes was observed in the hippocampus in adolescence and orbitofrontal cortex during infancy. Conclusions This study provides novel insights into the relationship between SCZ and AN by revealing a shared genetic component and offers a window into their complex etiology. [ABSTRACT FROM AUTHOR]

Key points Spatial information and dynamic locomotor behaviours are equally important for achieving locomotor goals during spatial navigation. However, it remains unclear how spatial and locomotor information is integrated during the processing of self‐initiated spatial navigation. Anatomically, the retrosplenial cortex (RSC) has reciprocal connections with brain regions related to spatial processing, including the hippocampus and para‐hippocampus, and also receives inputs from the secondary motor cortex. In addition, RSC is functionally associated with allocentric and egocentric spatial targets and head‐turning. So, RSC may be a critical region for integrating spatial and locomotor information. In this study, we first examined the role of RSC in spatial navigation using the Morris water maze and found that mice with inactivated RSC took a longer time and distance to reach their destination. Then, by imaging neuronal activity in freely behaving mice within two open fields of different sizes, we identified a large proportion of border cells, head‐turning cells and locomotor speed cells in the superficial layer of RSC. Interestingly, some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals. Furthermore, these conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigator scenes using the border, turning and positive‐speed conjunctive cells. Our study reveals that the RSC is an important conjunctive brain region that processes spatial and locomotor information during spatial navigation. Retrosplenial cortex (RSC) is indispensable during spatial navigation, which was displayed by the longer time and distance of mice to reach their destination after the inactivation of RSC in a water maze. The superficial layer of RSC has a larger population of spatial‐related border cells, and locomotion‐related head orientation and speed cells; however, it has few place cells in two‐dimensional spatial arenas. Some RSC neurons exhibited conjunctive coding for both spatial and locomotor signals, and the conjunctive neurons showed higher prediction accuracy compared with simple spatial or locomotor neurons in special navigation scenes. Our study reveals that the RSC is an important conjunctive brain region that processes both spatial and locomotor information during spatial navigation. [ABSTRACT FROM AUTHOR]

Key points Sharp wave‐ripple complexes (SPW‐Rs) are spontaneous oscillatory events that characterize hippocampal activity during resting periods and slow‐wave sleep. SPW‐Rs are related to memory consolidation – the process during which newly acquired memories are transformed into long‐lasting memory traces. To test the involvement of SPW‐Rs in this process, it is crucial to understand how SPW‐Rs originate and propagate throughout the hippocampus. SPW‐Rs can originate in CA3, and they typically spread from CA3 to CA1, but little is known about their formation within CA3. To investigate the generation and propagation of SPW‐Rs in CA3, we recorded from mouse hippocampal slices using multi‐electrode arrays and patch‐clamp electrodes. We characterized extracellular and intracellular correlates of SPW‐Rs and quantified their propagation along the pyramidal cell layer of CA3. We found that a hippocampal slice can be described by a speed and a direction of propagation of SPW‐Rs. The preferred propagation direction was from CA3c (the subfield closer to the dentate gyrus) toward CA3a (the subfield at the boundary to CA2). In patch‐clamp recordings from CA3 pyramidal neurons, propagation was estimated separately for excitatory and inhibitory currents associated with SPW‐Rs. We found that propagation speed and direction of excitatory and inhibitory currents were correlated. The magnitude of the speed of propagation of SPW‐Rs within CA3 was consistent with the speed of propagation of action potentials in axons of CA3 principal cells. Hippocampal sharp waves are considered important for memory consolidation; therefore, it is of interest to understand the mechanisms of their generation and propagation. Here, we used two different approaches to study the propagation of sharp waves in mouse CA3 in vitro: multi‐electrode arrays and multiple single‐cell recordings. We find a preferred direction of propagation of sharp waves from CA3c toward CA3a – both in the local field potential and in sharp wave‐associated excitatory and inhibitory synaptic activity. The speed of sharp wave propagation is consistent with the speed of action potential propagation along the axons of CA3 pyramidal neurons. These new insights into the dynamics of sharp waves in the CA3 network will inform future experiments and theoretical models of sharp‐wave generation mechanisms. [ABSTRACT FROM AUTHOR]

Opioid-associated brain injury may involve selective regions, including the hippocampi alone, globi pallidi, and cerebellar hemispheres. Opioid-associated amnestic syndrome, for example, is one clinical correlate of hippocampal injury as manifest by MRI abnormality. When all three regions are involved in what may be a more fulminant injury, the syndrome is termed "cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion (CHANTER)", initially described in 2019. Until now, to our knowledge, there have been no histopathologic correlates to the imaging findings specifically in CHANTER syndrome. Here, for the first time, we present histopathologic findings of the post-mortem brain from a patient who died from complications of CHANTER syndrome following fentanyl intoxication. These observations included microhemorrhage, reactive and necrotic vasculature, eosinophilic neuronal necrosis, axonal swelling and spheroids, and frank infarction. The findings support previous experimental models implicating both hypoxic–ischemic and cytotoxic mechanisms in the tissue damage associated with CHANTER syndrome, though further work is needed to better characterize the exact cellular pathways involved to develop targeted treatments. [ABSTRACT FROM AUTHOR]

The retrosplenial cortex (RSC) is a key component of the brain's memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In this study, we reanalyzed archival RSC neuronal firing data during the intertrial delay period from two previous experiments involving different behavioral tasks, a blocked alternation task and a cued T‐maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T‐maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off‐response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T‐maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory. [ABSTRACT FROM AUTHOR]

Magnetic resonance spectroscopy (MRS) has been employed to investigate brain metabolite concentrations in vivo, and they vary during neuronal activation, across brain activity states, or upon disease with neurological impact. Whether resting brain metabolites correlate with functioning in behavioral tasks remains to be demonstrated in any of the widely used rodent models. This study tested the hypothesis that, in the absence of neurological disease or injury, the performance in a hippocampal-dependent memory task is correlated with the hippocampal levels of metabolites that are mainly synthesized in neurons, namely N-acetylaspartate (NAA), glutamate and GABA. Experimentally naïve rats were tested for hippocampal-dependent spatial memory performance by measuring spontaneous alternation in the Y-maze, followed by anatomical magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in the hippocampus and cortex. Memory performance correlated with hippocampal concentrations of NAA (p = 0.024) and glutamate (p = 0.014) but not GABA. Concentrations of glutamate in the cortex also correlated with spatial memory (p = 0.035). In addition, memory performance was also correlated with the relative volume of the hippocampus (p = 0.041). Altogether, this exploratory study suggests that levels of the neuronal maker NAA and the main excitatory neurotransmitter glutamate are associated with physiological functional capacity. [ABSTRACT FROM AUTHOR]

Introduction: Neurobiological changes in the hippocampus are a common consequence of aging. However, there are differences in the rate of decline and overall volume loss in people with no cognitive impairment compared to those with mild cognitive impairment (MCI) and Alzheimer's disease (AD). This systematic literature review was conducted to determine the relationship between hippocampal atrophy and changes in hippocampal volume in the noncognitively impaired brain and those with MCI or AD. Methods: This systematic review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The PubMed database was searched up to September 15, 2022, for longitudinal magnetic resonance imaging studies reporting hippocampal atrophy or volume change in cognitively normal aging individuals and patients with MCI and/or AD. Study selection was divided into two steps: (1) identification and retrieval of relevant studies; (2) screening the studies by (a) title/abstract and (b) full text. Two teams, each consisting of two independent reviewers, determined whether the publications met the inclusion criteria for the systematic review. An evidence table was populated with data extracted from eligible publications and inclusion in the final systematic review was confirmed. Results: The systematic search identified 357 publications that were initially screened by title/abstract, of which, 115 publications were retrieved and reviewed by full text for eligibility. Seventeen publications met the eligibility criteria; however, during data extraction, two studies were determined to not meet the inclusion criteria and were excluded. The remaining 15 studies were included in the systematic review. Overall, the results of these studies demonstrated that the hippocampus and hippocampal subfields change over time, with both decreased hippocampal volume and increased rate of hippocampal atrophy observed. Hippocampal changes in AD were observed to be greater than hippocampal changes in MCI, and changes in MCI were observed to be greater than those in normal aging populations. Conclusion: Published literature suggests that the rate of hippocampal decline and extent of loss is on a continuum that begins in people without cognitive impairment and continues to MCI and AD, and that differences between no cognitive impairment, MCI, and AD are quantitative rather than qualitative. [ABSTRACT FROM AUTHOR]

Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainatemousemodel ofmesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10Hz and demonstrated the effects of different stimulation amplitudes (80-230 µA) and frequencies (1-100Hz) in epileptic mice. Motivated by recent studies exploring 1Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms. [ABSTRACT FROM AUTHOR]

The primate including the human hippocampus implicated in episodic memory and navigation represents a spatial view, very different from the place representations in rodents. To understand this system in humans, and the computations performed, the pathway for this spatial view information to reach the hippocampus was analysed in humans. Whole-brain effective connectivity was measured with magnetoencephalography between 30 visual cortical regions and 150 other cortical regions using the HCP-MMP1 atlas in 21 participants while performing a 0-back scene memory task. In a ventromedial visual stream, V1–V4 connect to the ProStriate region where the retrosplenial scene area is located. The ProStriate region has connectivity to ventromedial visual regions VMV1–3 and VVC. These ventromedial regions connect to the medial parahippocampal region PHA1–3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal regions have effective connectivity to the entorhinal cortex, perirhinal cortex, and hippocampus. In contrast, when viewing faces, the effective connectivity was more through a ventrolateral visual cortical stream via the fusiform face cortex to the inferior temporal visual cortex regions TE2p and TE2a. A ventromedial visual cortical 'Where' stream to the hippocampus for spatial scenes was supported by diffusion topography in 171 HCP participants at 7 T. A ventromedial cortical 'Where' visual pathway in humans for spatial scenes is revealed with MEG. It is fundamental to episodic memory and navigation. [ABSTRACT FROM AUTHOR]

The astrocyte-to-neuron lactate shuttle model entails that, upon glutamatergic neurotransmission, glycolytically derived pyruvate in astrocytes is mainly converted to lactate instead of being entirely catabolized in mitochondria. The mechanism of this metabolic rewiring and its occurrence in human brain are unclear. Here by using immunohistochemistry (4 brains) and imaging mass cytometry (8 brains) we show that astrocytes of the adult human neocortex and hippocampal formation express barely detectable amounts of mitochondrial proteins critical for performing oxidative phosphorylation (OXPHOS). These data are corroborated by queries of transcriptomes (107 brains) of neuronal versus non-neuronal cells fetched from the Allen Institute for Brain Science for genes coding for a much larger repertoire of entities contributing to OXPHOS, showing that human non-neuronal elements barely expressed mRNAs coding for such proteins. With less OXPHOS, human brain astrocytes are thus bound to produce more lactate to avoid interruption of glycolysis. Human brain astrocytes lack OXPHOS, ensuring lactate formation and shuttling to neurons. [ABSTRACT FROM AUTHOR]

Naturalistic observations show that animals pre-empt danger by moving to locations that increase their success in avoiding future threats. To test this in humans, we created a spatial margin of safety (MOS) decision task that quantifies pre-emptive avoidance by measuring the distance subjects place themselves to safety when facing different threats whose attack locations vary in predictability. Behavioral results show that human participants place themselves closer to safe locations when facing threats that attack in spatial locations with more outliers. Using both univariate and multivariate pattern analysis (MVPA) on fMRI data collected during a 2 h session on participants of both sexes, we demonstrate a dissociable role for the vmPFC in MOS-related decision-making. MVPA results revealed that the posterior vmPFC encoded for more unpredictable threats with univariate analyses showing a functional coupling with the amygdala and hippocampus. Conversely, the anterior vmPFC was more active for the more predictable attacks and showed coupling with the striatum. Our findings converge in showing that during pre-emptive danger, the anterior vmPFC may provide a safety signal, possibly via foreseeable outcomes, while the posterior vmPFC drives unpredictable danger signals. [ABSTRACT FROM AUTHOR]

To better understand neural processing during adaptive learning of stimulus‐response‐reward contingencies, we recorded synchrony of neuronal activity in anterior cingulate cortex (ACC) and hippocampal rhythms in male rats acquiring and switching between spatial and visual discrimination tasks in a Y‐maze. ACC population activity as well as single unit activity shifted shortly after task rule changes or just before the rats adopted different task strategies. Hippocampal theta oscillations (associated with memory encoding) modulated an elevated proportion of rule‐change responsive neurons (70%), but other neurons that were correlated with strategy‐change, strategy value and reward‐rate were not. However, hippocampal sharp wave‐ripples modulated significantly higher proportions of rule‐change, strategy‐change and reward‐rate responsive cells during post‐session sleep but not pre‐session sleep. This suggests an underestimated mechanism for hippocampal mismatch and contextual signals to facilitate ACC to detect contingency changes for cognitive flexibility, a function that is attenuated after it is damaged. [ABSTRACT FROM AUTHOR]

Background and objectives: Cognitive reserve (CR) is a property of the brain that allows for better-than-expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting-state EEG, moderate the relationship between hippocampal volume and episodic memory. Methods: Participants were recruited as part of the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson-Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal-memory association. Results: A total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of β = -0.00012 (95% CI: -0.00024; -0.00001, p = 0.040), and VAN with a slope of β = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond -914.6, the hippocampal volume was no longer significantly associated with word-list memory. Discussion: Our results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve. [ABSTRACT FROM AUTHOR]

Homocysteine (Hcy) is a cardiovascular risk factor implicated in cognitive impairment and cerebrovascular disease but has also been associated with Alzheimer's disease. In 160 healthy older adults (mean age = 69.66 ± 9.95 years), we sought to investigate the association of cortical brain volume with white matter hyperintensity (WMH) burden and a previously identified Hcy-related multivariate network pattern showing reductions in subcortical gray matter (SGM) volumes of hippocampus and nucleus accumbens with relative preservation of basal ganglia. We additionally evaluated the potential role of these brain imaging markers as a series of mediators in a vascular brain pathway leading to age-related cognitive dysfunction in healthy aging. We found reductions in parietal lobar gray matter associated with the Hcy-SGM pattern, which was further associated with WMH burden. Mediation analyses revealed that slowed processing speed related to aging, but not executive functioning or memory, was mediated sequentially through increased WMH lesion volume, greater Hcy-SGM pattern expression, and then smaller parietal lobe volume. Together, these findings suggest that volume reductions in parietal gray matter associated with a pattern of Hcy-related SGM volume differences may be indicative of slowed processing speed in cognitive aging, potentially linking cardiovascular risk to an important aspect of cognitive dysfunction in healthy aging. [ABSTRACT FROM AUTHOR]

Ageing is characterized by a gradual decline in the efficiency of physiological functions and increased vulnerability to diseases. Ageing affects the entire body, including physical, mental, and social well-being, but its impact on the brain and cognition can have a particularly significant effect on an individual's overall quality of life. Therefore, enhancing lifespan and physical health in longevity studies will be incomplete if cognitive ageing is over looked. Promoting successful cognitive ageing encompasses the objectives of mitigating cognitive decline, as well as simultaneously enhancing brain function and cognitive reserve. Studies in both humans and animal models indicate that cognitive decline related to normal ageing and age-associated brain disorders are more likely linked to changes in synaptic connections that form the basis of learning and memory. This activitydependent synaptic plasticity reorganises the structure and function of neurons not only to adapt to new environments, but also to remain robust and stable over time. Therefore, understanding the neural mechanisms that are responsible for age-related cognitive decline becomes increasingly important. In this review, we explore the multifaceted aspects of healthy brain ageing with emphasis on synaptic plasticity, its adaptive mechanisms and the various factors affecting the decline in cognitive functions during ageing. We will also explore the dynamic brain and neuroplasticity, and the role of lifestyle in shaping neuronal plasticity. [ABSTRACT FROM AUTHOR]

The development of biologically realistic models of brain microcircuits and regions constitutes currently a very relevant topic in computational neuroscience. One of the main challenges of such models is the passage between different scales, going from the microscale (cellular) to the meso (microcircuit) and macroscale (region or whole-brain level), while keeping at the same time a constraint on the demand of computational resources. In this paper we introduce a multiscale modeling framework for the hippocampal CA1, a region of the brain that plays a key role in functions such as learning, memory consolidation and navigation. Ourmodeling framework goes fromthe single cell level to the macroscale and makes use of a novel mean-field model of CA1, introduced in this paper, to bridge the gap between the micro and macro scales. We test and validate the model by analyzing the response of the system to the main brain rhythms observed in the hippocampus and comparing our results with the ones of the corresponding spiking network model of CA1. Then, we analyze the implementation of synaptic plasticity within our framework, a key aspect to study the role of hippocampus in learning and memory consolidation, and we demonstrate the capability of our framework to incorporate the variations at synaptic level. Finally, we present an example of the implementation of our model to study a stimulus propagation at the macro-scale level, and we show that the results of our framework can capture the dynamics obtained in the corresponding spiking network model of the whole CA1 area. [ABSTRACT FROM AUTHOR]

Background: Insomnia disorder (ID) is one of the most common sleep problems, usually accompanied by anxiety and depression symptoms. Functional magnetic resonance imaging (fMRI) study suggests that both poor sleep quality and negative emotion are linked to the dysregulation of brain network related to emotion processing in ID patients. Acupuncture therapy has been proven effective in improving sleep quality and mood of ID patients, but the involved neurobiological mechanism remains unclear. We aimed to investigate the modulation effect of acupuncture on resting-state functional connectivity (rsFC) of the emotional network (EN) in patients experiencing insomnia. Methods: A total of 30 healthy controls (HCs) and 60 ID patients were enrolled in this study. Sixty ID patients were randomly assigned to real and sham acupuncture groups and attended resting-state fMRI scans before and after 4 weeks of acupuncture treatment. HCs completed an MRI/fMRI scan at baseline. The rsFC values within EN were calculated, and Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), Hyperarousal Scale (HAS), and actigraphy data were collected for clinical efficacy evaluation. Results: Resting-state FC analysis showed abnormalities in rsFC centered on the thalamus and dorsolateral prefrontal cortex within EN of ID patients compared to HCs. After real acupuncture treatment, rsFC of the anterior cingulate cortex, hippocampus, and amygdala were increased compared with the sham acupuncture group (p < 0.05, FDR corrected). In real acupuncture group, the rsFC value was decreased between left amygdala and left thalamus after 4 weeks of treatment compared with baseline. A trend of correlation was found that the increased rsFC value between the right amygdala and left hippocampus was positively correlated with the decreased HAMA scores across all ID patients, and the decreased left amygdala rsFC value with the left thalamus was negatively correlated with the increased sleep efficiency in the real acupuncture group. Conclusion: Our findings showed that real acupuncture could produce a positive effect on modulating rsFC within network related to emotion processing in ID patients, which may illustrate the central mechanism underlying acupuncture for insomnia in improving sleep quality and emotion regulation. Trial registration: http://www.chictr.org.cn., ChiCTR1800015282, 20/03/2018. [ABSTRACT FROM AUTHOR]

The entorhinal cortex represents allocentric spatial geometry and egocentric speed and heading information required for spatial navigation. However, it remains unclear whether it contributes to the prediction of an animal's future location. We discovered grid cells in the medial entorhinal cortex (MEC) that have grid fields representing future locations during goal-directed behavior. These predictive grid cells represented prospective spatial information by shifting their grid fields against the direction of travel. Predictive grid cells discharged at the trough phases of the hippocampal CA1 theta oscillation and, together with other types of grid cells, organized sequences of the trajectory from the current to future positions across each theta cycle. Our results suggest that the MEC provides a predictive map that supports forward planning in spatial navigation. [ABSTRACT FROM AUTHOR]

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to cholecystokinin-expressing (CCK+) basket cells, which fire a barrage of action potentials (“BARR”) during non–rapid eye movement sleep. CA1 neurons and assemblies that increased their activity during learning were reactivated during SWRs but inhibited during BARRs. The initial increase in reactivation during SWRs returned to baseline through sleep. This trend was abolished by silencing CCK+ basket cells during BARRs, resulting in higher synchrony of CA1 assemblies and impaired memory consolidation. [ABSTRACT FROM AUTHOR]

The hippocampal CA3 region plays an important role in learning and memory. CA3 pyramidal neurons (PNs) receive two prominent excitatory inputs-mossy fibers (MFs) from dentate gyrus (DG) and recurrent collaterals (RCs) from CA3 PNs-that play opposing roles in pattern separation and pattern completion, respectively. Although the dorsoventral heterogeneity of the hippocampal anatomy, physiology, and behavior has been well established, nothing is known about the dorsoventral heterogeneity of synaptic connectivity in CA3 PNs. In this study, we performed Timm’s sulfide silver staining, dendritic and spine morphological analyses, and ex vivo electrophysiology in mice of both sexes to investigate the heterogeneity of MF and RC pathways along the CA3 dorsoventral axis. Our morphological analyses demonstrate that ventral CA3 (vCA3) PNs possess greater dendritic lengths and more complex dendritic arborization, compared with dorsal CA3 (dCA3) PNs. Moreover, using ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording, we found that the ratio of the RC-to-MF excitatory drive onto CA3 PNs increases substantially from dCA3 to vCA3, with vCA3 PNs receiving significantly weaker MFs, but stronger RCs, excitation than dCA3 PNs. Given the distinct roles of MF versus RC inputs in pattern separation versus completion, our findings of the significant dorsoventral variations of MF and RC excitation in CA3 PNs may have important functional implications for the contribution of CA3 circuit to the dorsoventral difference in hippocampal function [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common neurogenerative disorder without effective treatments. Defects in mitochondrial complex I are thought to contribute to AD pathogenesis. The aim of this study is to explore whether a novel gene therapy transducing yeast complex I gene NDI1 can be used to treat AD with severely reduced complex I function in cell and animal models. Methods: The differentiated human neural cells were induced by Aβ1–42 to establish the AD cell model, and adeno-associated virus serotype 9 (AAV9) was used to transduce yeast NDI1 into the cell model. Aβ1–42 was injected into the hippocampus area of the brain to establish the AD mouse model. AAV9-NDI1 was injected stereotaxically into the hippocampus area to test the therapeutic effect. Results: The expressed yeast complex I had an ameliorating effect on the defective function of human complex I and cellular pathological characteristics in the AD cell model. Furthermore, AAV9-NDI1 gene therapy in the hippocampus had a therapeutic effect on various aspects of mitochondrial function, histopathological characteristics and neurological defects in the AD mouse model. In addition, AAV9-NDI1 injection into the hippocampus of normal mice did not cause any adverse effect. Conclusions: Compensating mitochondrial complex I function with yeast NDI1 is effective for gene therapy in Aβ-induced AD cell and mouse models. The results of this study offer a novel strategy and approach for treating AD types characterized by complex I abnormalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Seahorses are iconic species facing population decline due to human action. Knowledge about seahorse distribution in Europe, particularly along the southwest coasts, remains scarce. This work has gathered information from diverse sources, including scientists, managers, professional fishermen, and the invaluable citizen-science platforms, resulting in novel information on the occurrence of two species of seahorses (Hippocampus hippocampus and H. guttulatus) in the Gulf of Cádiz and nearby areas. This study will allow for a more efficient management of local seahorse populations to safeguard their conservation. Achieving sustainable resource use is a priority to meet future challenges. The Gulf of Cádiz, located in the Atlantic waters of southern Europe, is home to a significant fishing fleet due to the richness and diversity of its ecosystems. Managing this area is complex due to the diversity of variables, including social, ecological, and oceanographic factors. Therefore, multidisciplinary approaches are proposed for implementing conservation strategies. One strategy for defining area-based management measures is through the use of flagship species, such as seahorses. These emblematic animals can assist in defining such measures. However, there is currently scarce information on the occurrence of seahorses in the Gulf of Cádiz. In this study, we present the first occurrence data of two species of the genus Hippocampus (H. hippocampus and H. guttulatus) in this area. The Gulf of Cádiz is not only described as the southernmost region of their distribution in continental Europe, but it is also a significant landmark for the genus Hippocampus, as one adult was captured at a depth of up to 101 m. Five management areas based on differentiated benthic habitats are proposed. We believe that our study has the potential to significantly improve conservation of seahorses and induce a positive impact on the ecosystem. [ABSTRACT FROM AUTHOR]

The intracerebral spread of tau is a critical mechanism associated with functional decline in Alzheimer's disease (AD) and other tauopathies. Recently, a hypothesis has emerged suggesting that tau propagation is linked to functional neuronal connections, specifically driven by neuronal hyperactivity. However, experimental validation of this hypothesis remains limited. In this study, we investigated how tau propagation from the entorhinal cortex to the hippocampus, the neuronal circuit most susceptible to tau pathology in AD, is affected by the selective stimulation of neuronal activity along this circuit. Using a mouse model of seed-induced propagation combined with optogenetics, we found that the chronic stimulation of this neuronal connection over a 4-week period resulted in a significant increase in insoluble tau accumulation in both the entorhinal cortex and hippocampus. Importantly, the ratio of tau accumulation in the hippocampus relative to that in the entorhinal cortex, serving as an indicator of transcellular spreading, was significantly higher in mice subjected to chronic stimulation. These results support the notion that abnormal neuronal activity promotes tau propagation, thereby implicating it in the progression of tauopathy. [ABSTRACT FROM AUTHOR]

Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM [ABSTRACT FROM AUTHOR]