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1
Babb, Thomas L. "Bilateral Pathological Damage in Temporal Lobe Epilepsy." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 18, S4 (November 1991): 645–48. http://dx.doi.org/10.1017/s031716710003287x.
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ABSTRACT:Patients with drug-refractory temporal lobe epilepsy can be treated successfully with surgical resection of one temporal lobe, especially when the resection includes the hippocampus. Although intrahippocampal recordings usually localize seizure onsets to one hippocampus, there are bilaterally-independent interictal spikes, occasional contralateral seizure onsets and post-resection seizures that implicate contralateral damage and epileptogenicity. Post-mortem onquantified studies of both hippocampi in epileptics have revealed incidences of bilateral hippocampal sclerosis, mostly being asymmetric. The present paper reports on two post-mortem cases of bilateral, asymmetric cell loss in patients with physiologically-verified hippocampal epilepsy. In one patient the damage was severe bilaterally, but only slightly greater damage in one hippocampus. In the second patient, damage in one hippocampus was as severe as in the first patient; however the contralateral hippocampus appeared undamaged. However, cell counts revealed losses of over 30% in three different hippocampal subregions, indicating a mild form of asymmetric bilateral damage in patient two.
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Dobryakova, Yulia V., Konstantin Gerasimov, Yulia S. Spivak, Tinna Korotkova, Alena Koryagina, Angelina Deryabina, Vladimir A. Markevich, and Alexey P. Bolshakov. "The Induction of Long-Term Potentiation by Medial Septum Activation under Urethane Anesthesia Can Alter Gene Expression in the Hippocampus." International Journal of Molecular Sciences 24, no. 16 (August 19, 2023): 12970. http://dx.doi.org/10.3390/ijms241612970.
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We studied changes in the expression of early genes in hippocampal cells in response to stimulation of the dorsal medial septal area (dMSA), leading to long-term potentiation in the hippocampus. Rats under urethane anesthesia were implanted with stimulating electrodes in the ventral hippocampal commissure and dMSA and a recording electrode in the CA1 area of the hippocampus. We found that high-frequency stimulation (HFS) of the dMSA led to the induction of long-term potentiation in the synapses formed by the ventral hippocampal commissure on the hippocampal CA1 neurons. One hour after dMSA HFS, we collected the dorsal and ventral hippocampi on both the ipsilateral (damaged by the implanted electrode) and contralateral (intact) sides and analyzed the expression of genes by qPCR. The dMSA HFS led to an increase in the expression of bdnf and cyr61 in the ipsilateral hippocampi and egr1 in the ventral contralateral hippocampus. Thus, dMSA HFS under the conditions of degeneration of the cholinergic neurons in the medial septal area prevented the described increase in gene expression. The changes in cyr61 expression appeared to be dependent on the muscarinic M1 receptors. Our data suggest that the induction of long-term potentiation by dMSA activation enhances the expression of select early genes in the hippocampus.
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Zhang, Jia-He, Takashi Tasaki, Manabu Tsukamoto, Ke-Yong Wang, Kin-ya Kubo, and Kagaku Azuma. "Deletion of Wnt10a Is Implicated in Hippocampal Neurodegeneration in Mice." Biomedicines 10, no. 7 (June 25, 2022): 1500. http://dx.doi.org/10.3390/biomedicines10071500.
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The hippocampus plays an important role in maintaining normal cognitive function and is closely associated with the neuropathogenesis of dementia. Wnt signaling is relevant to neuronal development and maturation, synaptic formation, and plasticity. The role of Wnt10a in hippocampus-associated cognition, however, is largely unclear. Here, we examined the morphological and functional alterations in the hippocampus of Wnt10a-knockout (Wnt10a-/-) mice. Neurobehavioral tests revealed that Wnt10a-/- mice exhibited spatial memory impairment and anxiety-like behavior. Immunostaining and Western blot findings showed that the protein expressions of β-catenin, brain-derived neurotrophic factor, and doublecortin were significantly decreased and that the number of activated microglia increased, accompanied by amyloid-β accumulation, synaptic dysfunction, and microglia-associated neuroinflammation in the hippocampi of Wnt10a-/- mice. Our findings revealed that the deletion of Wnt10a decreased neurogenesis, impaired synaptic function, and induced hippocampal neuroinflammation, eventually leading to hippocampal neurodegeneration and memory deficit, possibly through the β-catenin signaling pathway, providing a novel insight into preventive approaches for hippocampus-dependent cognitive impairment.
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Spivak, Yulia S., Anna A. Karan, Yulia V. Dobryakova, Tatiana M. Medvedeva, Vladimir A. Markevich, and Alexey P. Bolshakov. "Deep Brain Stimulation of the Medial Septal Area Can Modulate Gene Expression in the Hippocampus of Rats under Urethane Anesthesia." International Journal of Molecular Sciences 23, no. 11 (May 27, 2022): 6034. http://dx.doi.org/10.3390/ijms23116034.
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We studied the effects of stimulation of the medial septal area on the gene expression in the dorsal and ventral hippocampus. Rats under urethane anesthesia were implanted with a recording electrode in the right hippocampus and stimulating electrode in the dorsal medial septum (dMS) or medial septal nucleus (MSN). After one-hour-long deep brain stimulation, we collected ipsi- and contralateral dorsal and ventral hippocampi. Quantitative PCR showed that deep brain stimulation did not cause any changes in the intact contralateral dorsal and ventral hippocampi. A comparison of ipsi- and contralateral hippocampi in the control unstimulated animals showed that electrode implantation in the ipsilateral dorsal hippocampus led to a dramatic increase in the expression of immediate early genes (c-fos, arc, egr1, npas4), neurotrophins (ngf, bdnf) and inflammatory cytokines (il1b and tnf, but not il6) not only in the area close to implantation site but also in the ventral hippocampus. Moreover, the stimulation of MSN but not dMS further increased the expression of c-fos, egr1, npas4, bdnf, and tnf in the ipsilateral ventral but not dorsal hippocampus. Our data suggest that the activation of medial septal nucleus can change the gene expression in ventral hippocampal cells after their priming by other stimuli.
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Goda, Jayant S., Debnarayan Dutta, Uday Krishna, Savita Goswami, Vikas Kothavade, Sadhna Kannan, Madan Maitre, Nazia Bano, Tejpal Gupta, and Rakesh Jalali. "Hippocampal radiotherapy dose constraints for predicting long-term neurocognitive outcomes: mature data from a prospective trial in young patients with brain tumors." Neuro-Oncology 22, no. 11 (March 30, 2020): 1677–85. http://dx.doi.org/10.1093/neuonc/noaa076.
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Abstract Background Hippocampus is considered to be the seat for neurocognitive functions. Avoidance of hippocampus during radiotherapy to brain may serve to preserve various domains of neurocognition. We aimed to derive radiotherapy dose constraints to hippocampi for preserving neurocognition in young patients with brain tumors by measuring various neurocognitive parameters. Methods Forty-eight patients with residual/progressive benign or low-grade brain tumors treated with stereotactic conformal radiotherapy (SCRT) to a dose of 54 Gy in 30 fractions underwent prospective neuropsychological assessments at baseline before SCRT and at 6 months and 2, 3, 4, and 5 years. Hippocampi were drawn as per the Radiation Therapy Oncology Group atlas. Longitudinal change in intelligence quotient scores was correlated with hippocampal doses. Results Mean volume of bilateral hippocampi was 4.35 cc (range: 2.12–8.41 cc). Craniopharyngioma was the commonest histologic subtype. A drop of >10% in mean full-scale intelligence quotient (FSIQ) scores at 3 and 5 years post SCRT was observed in patients in whom left hippocampus received a mean dose of 30.7 Gy (P = 0.04) and 31 Gy (P = 0.04), respectively. Mean performance quotient (PQ) scores dropped > 10% at 5 years when the left hippocampus received a dose of > 32 Gy (P = 0.03). There was no significant correlation of radiotherapy doses with verbal quotient, or with doses received by the right hippocampus. Multivariate analysis revealed young age (<13 y) and left hippocampus dose predicted for clinically relevant decline in certain neurocognitive domains. Conclusions A mean dose of ≤30 Gy to the left hippocampus as a dose constraint for preserving intelligence quotient is suggested. Key Points 1. Children and young adults with benign and low-grade gliomas survive long after therapy. 2. Higher dose to the hippocampi may result in long-term neurocognitive impairment. 3. Mean dose of <30 Gy to left hippocampus could be used as a pragmatic dose constraint to prevent long-term neurocognitive decline.
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Ang, Mary Jasmin, Sueun Lee, Mai Wada, Poornima D. E. Weerasinghe-Mudiyanselage, Sung-Ho Kim, Taekyun Shin, Tae-Il Jeon, Seung-Soon Im, and Changjong Moon. "SREBP-1c Deficiency Affects Hippocampal Micromorphometry and Hippocampus-Dependent Memory Ability in Mice." International Journal of Molecular Sciences 22, no. 11 (June 5, 2021): 6103. http://dx.doi.org/10.3390/ijms22116103.
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Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.
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Seress, László, Hajnalka Ábrahám, Zsolt Horváth, Tamás Dóczi, József Janszky, Joyce Klemm, Richard Byrne, and Roy A. E. Bakay. "Survival of mossy cells of the hippocampal dentate gyrus in humans with mesial temporal lobe epilepsy." Journal of Neurosurgery 111, no. 6 (December 2009): 1237–47. http://dx.doi.org/10.3171/2008.11.jns08779.
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Object Hippocampal sclerosis can be identified in most patients with mesial temporal lobe epilepsy (TLE). Surgical removal of the sclerotic hippocampus is widely performed to treat patients with drug-resistant mesial TLE. In general, both epilepsy-prone and epilepsy-resistant neurons are believed to be in the hippocampal formation. The hilar mossy cells of the hippocampal dentate gyrus are usually considered one of the most vulnerable types of neurons. The aim of this study was to clarify the fate of mossy cells in the hippocampus in epileptic humans. Methods Of the 19 patients included in this study, 15 underwent temporal lobe resection because of drug-resistant TLE. Four patients were used as controls because they harbored tumors that had not invaded the hippocampus and they had experienced no seizures. Histological evaluation of resected hippocampal tissues was performed using immunohistochemistry. Results Mossy cells were identified in the control as well as the epileptic hippocampi by using cocaine- and amphetamine-regulated transcript peptide immunohistochemistry. In most cases the number of mossy cells was reduced and thorny excrescences were smaller in the epileptic hippocampi than in controls; however, there was a significant loss of pyramidal cells and a partial loss of granule cells in the same epileptic hippocampi in which mossy cell loss was apparent. The loss of mossy cells could be correlated with the extent of hippocampal sclerosis, patient age at seizure onset, duration of epilepsy, and frequency of seizures. Conclusions In many cases large numbers of mossy cells were present in the hilus of the dentate gyrus when most pyramidal neurons of the CA1 and CA3 areas of the Ammon's horn were lost, suggesting that mossy cells may not be more vulnerable to epileptic seizures than the hippocampal pyramidal neurons.
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Hanycz, Shaun Andrew, Alborz Noorani, Peter Shih-Ping Hung, Matthew R. Walker, Ashley B. Zhang, Timur H. Latypov, and Mojgan Hodaie. "Hippocampus diffusivity abnormalities in classical trigeminal neuralgia." PAIN Reports 9, no. 3 (April 19, 2024): e1159. http://dx.doi.org/10.1097/pr9.0000000000001159.
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Abstract Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.
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Dias Duarte Machado, Luiz Gabriel, Lior Mevorach, Victor De Oliveira Corrêa, Maria Eugênia Martins Publio Correa, Gabriel Phillip Sinibaldi Eagers, Guilherme Rodrigues Guidoni, Antonio Santoro, and Paulo Henrique Pires de Aguiar. "Study of hippocampal size and age." Italian Journal of Anatomy and Embryology 125, no. 1 (April 29, 2022): 59–65. http://dx.doi.org/10.36253/ijae-11867.
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Objective (or background): The hippocampus is a thoroughly studied structure of the temporal lobe. In contrast to our current knowledge of hippocampal anatomy, neurophysiology and pathophysiology, scientific literature on the relationship between the hippocampal size and age is limited. Our study aims to further the understanding of this relationship. Methods: 16 hippocampi were anatomized, photographed, measured and analyzed in comparison to age and gender using Pearson and bootstrap analyses with IBM SPSS®. Results: The results for all three independent variables of size, age and gender were not statistically significant. Conclusions: We were unable to show a statistically significant result on the correlation between the size of the hippocampus and age due to small sample size.
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Leskinen, Sandra, Harshal Shah, Morana Vojnic, Beril Yaffe, Shonna Schneider, Randy D'Amico, and A. Gabriella Wernicke. "RADT-03. A CASE OF PARTIAL HIPPOCAMPAL-AVOIDANCE WHOLE BRAIN RADIOTHERAPY IN A PATIENT WITH METASTATIC INFILTRATION OF THE LEFT HIPPOCAMPUS." Neuro-Oncology 25, Supplement_5 (November 1, 2023): v48. http://dx.doi.org/10.1093/neuonc/noad179.0192.
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Abstract In addition to surgical resection and systemic therapy, whole brain radiotherapy (WBRT) is a crucial modality in the treatment of cancers that have metastasized to the brain. It has been shown to improve intracranial disease control and overall survival. However, WBRT also increases the risk of radiation-associated damage to sensitive structures like the hippocampus, often resulting in neurocognitive dysfunction and decline. Hippocampal avoidance WBRT (HAWBRT) has been shown to reduce neurocognitive sequalae without worsening survival outcomes or increasing the risk of metastasis to the spared region compared to conventional WBRT. In cases where both hippocampi cannot be completely spared, the effectiveness of partial hippocampal avoidance on neurocognitive function and tumor control have been poorly described. We present the case of a patient diagnosed with triple negative invasive ductal carcinoma of the breast and disease metastatic to the brain, lung, bones, adrenal glands, and liver. Brain imaging revealed multiple brain metastases, two of which were noted near the left hippocampus. The patient underwent partial HAWBRT with complete avoidance of the right hippocampus and partial avoidance of the left. At 1-year follow-up, there was no evidence of metastasis in or near the partially spared left hippocampus. The patient’s neurocognitive functional status remained consistent with the findings of prospective randomized trials in which total bilateral hippocampal sparing was performed. To our knowledge, no such case has been presented in the literature. Further studies assessing the role of partial hippocampal avoidance in WBRT are needed.
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Weerasinghe-Mudiyanselage, Poornima D. E., Sohi Kang, Joong-Sun Kim, Jong-Choon Kim, Sung-Ho Kim, Hongbing Wang, Taekyun Shin, and Changjong Moon. "Transcriptome Profiling in the Hippocampi of Mice with Experimental Autoimmune Encephalomyelitis." International Journal of Molecular Sciences 23, no. 23 (November 27, 2022): 14829. http://dx.doi.org/10.3390/ijms232314829.
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Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), approximates the key histopathological, clinical, and immunological features of MS. Hippocampal dysfunction in MS and EAE causes varying degrees of cognitive and emotional impairments and synaptic abnormalities. However, the molecular alterations underlying hippocampal dysfunctions in MS and EAE are still under investigation. The purpose of this study was to identify differentially expressed genes (DEGs) in the hippocampus of mice with EAE in order to ascertain potential genes associated with hippocampal dysfunction. Gene expression in the hippocampus was analyzed by RNA-sequencing and validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene expression analysis revealed 1202 DEGs; 1023 were upregulated and 179 were downregulated in the hippocampus of mice with EAE (p-value < 0.05 and fold change >1.5). Gene ontology (GO) analysis showed that the upregulated genes in the hippocampi of mice with EAE were associated with immune system processes, defense responses, immune responses, and regulation of immune responses, whereas the downregulated genes were related to learning or memory, behavior, and nervous system processes in the GO biological process. The expressions of hub genes from the search tool for the retrieval of interacting genes/proteins (STRING) analysis were validated by RT-qPCR. Additionally, gene set enrichment analysis showed that the upregulated genes in the hippocampus were associated with inflammatory responses: interferon-γ responses, allograft rejection, interferon-α responses, IL6_JAK_STAT3 signaling, inflammatory responses, complement, IL2_STAT5 signaling, TNF-α signaling via NF-κB, and apoptosis, whereas the downregulated genes were related to synaptic plasticity, dendritic development, and development of dendritic spine. This study characterized the transcriptome pattern in the hippocampi of mice with EAE and signaling pathways underpinning hippocampal dysfunction. However, further investigation is needed to determine the applicability of these findings from this rodent model to patients with MS. Collectively, these results indicate directions for further research to understand the mechanisms behind hippocampal dysfunction in EAE.
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Espinal, Elizabeth, Akash Mishra, Evangelia G. Chrysikou, Ashesh Mehta, and Stephan Bickel. "5 Combining Neurophysiology and Behavioral Measures to Identify Biomarkers of Clinical and Preclinical Hippocampus-Dependent Memory Dysfunction." Journal of the International Neuropsychological Society 29, s1 (November 2023): 679–80. http://dx.doi.org/10.1017/s1355617723008524.
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Objective:Memory is a critical piece of the human experience and impairments in neural memory networks can have devastating consequences for the affected person. A subtype of memory, episodic memory generates context for the present based on past experience and allows us to make predictions about the future. Episodic memories become stable fixtures through long-term memory consolidation. It is believed that consolidation of episodic memory requires a dynamic interplay between connected hippocampal-cortical networks, mainly during sleep. Sleep oscillations, slow oscillations and thalamocortical spindles, coupled with hippocampal sharp wave ripples (SWR) is proposed to be mechanistically involved in establishing the crucial cortical-subcortical dialog. The current study aimed to determine alterations in typical sleep oscillations and oscillation coupling in patients with and without structural hippocampal damage and correlate them with neuropsychological measures believed to be sensitive to hippocampal dysfunction, i.e., Rey Auditory Verbal Learning Task (RAVLT) and Verbal Paired Associates (VPA-II).Participants and Methods:We used intracranial electroencephalography (iEEG) in 14 patients with epilepsy to directly record hippocampal and neocortical oscillations and neuropsychological measures obtained prior to implantation. Half of the participants were diagnosed with mesial temporal sclerosis (MTS) in the left hippocampus and healthy tissue in the right hippocampus. The other half did not have MTS and had either mesial temporal epilepsy without MTS or extra-temporal seizures. We analyzed hippocampal SWR output from both hippocampi and characterized neocortical slow oscillations and spindles and their coupling for each participant. We correlated electrophysiological data with behavioral results of neuropsychological testing in order to characterize the clinical relevance.Results:SWR analysis revealed significant differences in the frequency, t(7639) = 15.52, p>.001, p > .001), amplitude, t(7664) = -23.93, p > .001, and waveforms (p > .001) of SWR in the sclerotic versus healthy hippocampi. Patients with a sclerotic hippocampus but relatively preserved verbal memory scores (RAVLT, VPA-II) showed increased SWR amplitudes in the contralateral hippocampus compared to patients with low verbal memory scores. Additionally, we found differences between hemispheres in phase amplitude coupling of SWRs to spindles and SOs (p > 0.001). Results of our correlational analysis were variable and dependent upon additional factors, such as age of onset and diagnosis duration.Conclusions:Results from this work will aid in establishing a criterion for characterizing a relationship between subcortical and cortical oscillations as they relate to memory performance. Besides aiding our understanding of the neural mechanisms underpinning memory consolidation this will ideally help with developing neurophysiological biomarkers that may predict possible memory decline in resective or ablative neurosurgery absent of structural lesion. In addition, this work may potentially provide first evidence of a neurophysiological biomarker directly recorded from the human hippocampus to support possible reorganization of memory functioning in the non-sclerotic hippocampus.
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Pereira, D., M. Freschi, R. Frittoli, A. C. Londe, T. Amaral, S. Dertkigil, A. P. Del Rio, F. Cendes, L. Rittner, and S. Appenzeller. "AB0457 HIPPOCAMPAL SUBFIELDS VOLUMES REDUCTION IN PATIENTS WITH SYSTEMIC SCLEROSIS: A LONGITUDINAL MAGNETIC RESONANCE IMAGING (MRI) VOLUMETRIC STUDY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1255.2–1256. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3815.
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Background:Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs. In addition, volume reduction and shape abnormality of the hippocampus have been demonstrated in rheumatic and neurodegenerative diseases. However, the neuroanatomy of the hippocampus is complex and is not a uniform structure, consisting of subfields with distinct morphology: cornu ammonis (CA) subfields CA1–4, dentate gyrus (DG), fimbria, and adjacent subiculum and presubiculum [1].Objectives:To investigate the hippocampal subfields volumes reduction in SSc patients using MRI.Methods:In this study we included 37 SSc patients (33 women, mean age of 53.46, SD ± 12.29; range 30 - 78) and 37 healthy controls (HC) (31 women, mean age of 48.41, SD±12.20; range 29 - 80). Cognitive evaluation was performed using the Montreal Cognitive Assessment (MoCA), mood disorders were determined through Beck’s Depression (BDI) and Beck’s Anxiety Inventories (BAI). SSc patients were further assessed for clinical and laboratory SSc manifestations, disease activity (Valentini Activity Index), severity activity (Medsger Severity Index). MRI protocol consisted of: Sagittal T1-weighted images performed with a Philips 3.0T MRI scanner. MRI brain structure volumetric was done through volBrain [2]. After 48 months MRI acquisition were repeated in 26 SSc patients and 12 healthy volunteers. Statistics was performed according nature of the variable.Results:We observed a significant reduction in hippocampal subfields volumes in SSc patients when compared to controls: Total hippocampi (SSc: mean volume = 4.78 cm3; SD = 0.38; HC: mean volume = 5.01 cm3; SD = 0.38; p = 0.033). Reduction in volume of the total hippocampi was associated with Raynaud’s phenomenon (p = 0.006). A longitudinal study showed a reduction in volume of the hippocampus subfields volumes when compared to patient’s baseline: Total hippocampi (mean initial volume = 4.78 cm3; mean follow-up volume = 4.50 cm3, p = 0.027); Total CA1 (mean initial volume = 1.59 cm3; mean follow-up volume = 1.58 cm3, p < 0.0001); Reduction in volume of the total hippocampi was associated with presence of current use of prednisone (p = 0.008). Reduction in left CA1 left associated with current use of prednisone (p = 0.014). Reduction in total subiculum was associated with presence of calcinosis (p = 0.023). No significant changes were observed in hippocampal subfields volumes in controls over the follow-up period.Conclusion:This study provides evidence of hippocampus subfields volumes reductions in SSc patients when compared to controls and was associated with Raynaud’s phenomenon, current use of losartan and correlated with BAI scores. Also, a longitudinal study showed a reduction in volume of the hippocampus subfields volumes when compared to patient’s baseline associated with calcinosis and current use of prednisone.References:[1]Eichenbaum, Howard. “A cortical–hippocampal system for declarative memory.” Nature Reviews Neuroscience 1.1 (2000): 41-50.[2]Manjon JV, Coupe P (2016) volBrain: an online MRI brain volumetry system. Front Neuroinform 10:30.Disclosure of Interests:None declared.
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Erdem, Atilla, M. Gazi Yaşargil, and Peter Roth. "Microsurgical anatomy of the hippocampal arteries." Journal of Neurosurgery 79, no. 2 (August 1993): 256–65. http://dx.doi.org/10.3171/jns.1993.79.2.0256.
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✓ An anatomical study of the vascularization of the hippocampus was performed on 30 hemispheres. There were a total of 140 arteries supplying the hippocampi, for an average of 4.7 arteries per hemisphere (range three to seven arteries). Based on the origin and caliber of the arteries supplying the hippocampus, the hemispheres were divided into five groups: A) in 57% of the hemispheres studied, the origin was mixed and included the anterior choroidal artery (AChA), the main trunk of the posterior cerebral artery (PCA), and the inferior temporal, lateral posterior choroidal, and splenial branches of the PCA; B) in 27%, all of the inferior temporal branches of the PCA predominantly supplied the hippocampus; C) in 10%, the anterior inferior temporal branch of the PCA was the predominant supplier: D) in 3%, the hippocampus was predominantly supplied by arteries originating from the main trunk of the PCA (Uchimura artery); and E) in 3%, the AChA gave origin to the hippocampal vessel. It was found as a result of this study that the PCA directly and by its branches contributes much more to the blood supply of the hippocampal formation than the AChA. The uncal sulcus was found to be an important anastomotic site between the hippocampal branches of the AChA and the hippocampal branches of the PCA. In 26.6% of hemispheres, one of the hippocampal arteries arose from the lateral posterior choroidal artery. The splenial artery made a loop close to the extra ventricular part of the hippocampal tail and gave off multiple vessels to this structure in 36.6% of hemispheres. The finding that the AChA passes through the choroid fissure as a trunk and its later division into the lateral plexal and medial perforating branches within the choroid plexus may be of surgical significance.
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Lathe, R. "Hormones and the hippocampus." Journal of Endocrinology 169, no. 2 (May 1, 2001): 205–31. http://dx.doi.org/10.1677/joe.0.1690205.
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Hippocampal lesions produce memory deficits, but the exact function of the hippocampus remains obscure. Evidence is presented that its role in memory may be ancillary to physiological regulation. Molecular studies demonstrate that the hippocampus is a primary target for ligands that reflect body physiology, including ion balance and blood pressure, immunity, pain, reproductive status, satiety and stress. Hippocampal receptors are functional, probably accessible to their ligands, and mediate physiological and cognitive changes. This argues that an early role of the hippocampus may have been in sensing soluble molecules (termed here 'enteroception') in blood and cerebrospinal fluid, perhaps reflecting a common evolutionary origin with the olfactory system ('exteroception'). Functionally, hippocampal enteroception may reflect feedback control; evidence is reviewed that the hippocampus modulates body physiology, including the activity of the hypothalamus-pituitary-adrenal axis, blood pressure, immunity, and reproductive function. It is suggested that the hippocampus operates, in parallel with the amygdala, to modulate body physiology in response to cognitive stimuli. Hippocampal outputs are predominantly inhibitory on downstream neuroendocrine activity; increased synaptic efficacy in the hippocampus (e.g. long-term potentiation) could facilitate throughput inhibition. This may have implications for the role of the hippocampus and long-term potentiation in memory.
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Kazda, Tomas, Adela Misove, Petr Burkon, Petr Pospisil, Ludmila Hynkova, Iveta Selingerova, Adam Dziacky, et al. "Incidence of Hippocampal Metastases: Laterality and Implications for Unilateral Hippocampal Avoiding Whole Brain Radiotherapy." BioMed Research International 2018 (December 13, 2018): 1–7. http://dx.doi.org/10.1155/2018/2459608.
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Introduction. Hippocampi sparing whole brain radiotherapy (WBRT) is an evolving approach in the treatment of patients with multiple brain metastases, pursuing mitigation of verbal memory decline as a consequence of hippocampal radiation injury. Accumulating data are showing different postradiotherapy changes in the left and right hippocampus with a theoretical proposal of only unilateral (dominant, left) hippocampal sparing during WBRT. Method. The aim of this retrospective study is to describe spatial distribution of brain metastases on MRI in a cohort of 260 patients (2595 metastases) and to evaluate distribution separately in the left and right hippocampus and in respective hippocampal avoiding zones (HAZ, region with subtherapeutic radiation dose), including evaluation of location of metastatic mass centre. Results. The median number of brain metastases was three, with lung cancer being the most common type of primary tumour; 36% had single metastasis. Almost 8% of patients had metastasis within hippocampus (1.1% of all metastases) and 18.1% of patients within HAZ (3.3% of all metastases). No statistically significant difference was observed in the laterality of hippocampal involvement, also when the location of centre of metastases was analyzed. There were more patients presenting the centre of metastasis within left (15) versus right (6) HAZ approaching the borderline of statistical significance. Conclusion. No significant difference in the laterality of BM seeding within hippocampal structures was observed. The hypothesized unilateral sparing WBRT would have theoretical advantage in about 50% reduction in the risk of subsequent recurrence within spared regions.
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Kouhnavardi, Shima, Maureen Cabatic, M. Carmen Mañas-Padilla, Marife-Astrid Malabanan, Tarik Smani, Ana Cicvaric, Edison Alejandro Muñoz Aranzalez, et al. "miRNA-132/212 Deficiency Disrupts Selective Corticosterone Modulation of Dorsal vs. Ventral Hippocampal Metaplasticity." International Journal of Molecular Sciences 24, no. 11 (May 31, 2023): 9565. http://dx.doi.org/10.3390/ijms24119565.
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Cortisol is a potent human steroid hormone that plays key roles in the central nervous system, influencing processes such as brain neuronal synaptic plasticity and regulating the expression of emotional and behavioral responses. The relevance of cortisol stands out in the disease, as its dysregulation is associated with debilitating conditions such as Alzheimer’s Disease, chronic stress, anxiety and depression. Among other brain regions, cortisol importantly influences the function of the hippocampus, a structure central for memory and emotional information processing. The mechanisms fine-tuning the different synaptic responses of the hippocampus to steroid hormone signaling remain, however, poorly understood. Using ex vivo electrophysiology and wild type (WT) and miR-132/miR-212 microRNAs knockout (miRNA-132/212−/−) mice, we examined the effects of corticosterone (the rodent’s equivalent to cortisol in humans) on the synaptic properties of the dorsal and ventral hippocampus. In WT mice, corticosterone predominantly inhibited metaplasticity in the dorsal WT hippocampi, whereas it significantly dysregulated both synaptic transmission and metaplasticity at dorsal and ventral regions of miR–132/212−/− hippocampi. Western blotting further revealed significantly augmented levels of endogenous CREB and a significant CREB reduction in response to corticosterone only in miR–132/212−/− hippocampi. Sirt1 levels were also endogenously enhanced in the miR–132/212−/− hippocampi but unaltered by corticosterone, whereas the levels of phospo-MSK1 were only reduced by corticosterone in WT, not in miR–132/212−/− hippocampi. In behavioral studies using the elevated plus maze, miRNA-132/212−/− mice further showed reduced anxiety-like behavior. These observations propose miRNA-132/212 as potential region-selective regulators of the effects of steroid hormones on hippocampal functions, thus likely fine-tuning hippocampus-dependent memory and emotional processing.
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Green, C. R., L. T. Watts, S. M. Kobus, G. I. Henderson, J. N. Reynolds, and J. F. Brien. "Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2α concentrations in the hippocampus of the perinatal guinea pig." Reproduction, Fertility and Development 18, no. 5 (2006): 517. http://dx.doi.org/10.1071/rd05128.
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It is hypothesised that oxidative stress is a key mechanism of ethanol neurobehavioural teratogenicity, resulting in altered endogenous antioxidant status and increased membrane lipid peroxidation in the hippocampus of chronic prenatal ethanol exposure (CPEE) offspring. To test this hypothesis, timed pregnant guinea-pigs (term, approximately gestational day (GD) 68) received chronic daily oral administration of (i) 4 g ethanol kg–1 maternal bodyweight, (ii) isocaloric sucrose with pair feeding, or (iii) water. At GD 65 (term fetus) and postnatal day (PD) 0 (neonate), individual offspring were killed, the brain was excised and the hippocampi were dissected. Glutathione (GSH) concentration was measured in the cytosolic and mitochondrial fractions of hippocampal homogenate. The occurrence of lipid peroxidation was determined by measuring the concentration of 8-iso-prostaglandin F2α (8-iso-PGF2α). There was CPEE-induced decreased brain weight and hippocampal weight at GD 65 and PD 0, decreased mitochondrial GSH concentration in the hippocampus at PD 0, with no change in mitochondrial GSH concentration at GD 65 or cytosolic GSH concentration at GD 65 or PD 0, and no change in mitochondrial or whole-homogenate 8-iso-PGF2α concentration in the hippocampus at GD 65 or PD 0. The data demonstrate that CPEE produces selective mitochondrial dysfunction in the hippocampus of the neonatal guinea-pig, involving GSH depletion.
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Nobakht, Samaneh, Morgan Schaeffer, Nils D. Forkert, Sean Nestor, Sandra E. Black, and Philip Barber. "Combined Atlas and Convolutional Neural Network-Based Segmentation of the Hippocampus from MRI According to the ADNI Harmonized Protocol." Sensors 21, no. 7 (April 1, 2021): 2427. http://dx.doi.org/10.3390/s21072427.
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Hippocampus atrophy is an early structural feature that can be measured from magnetic resonance imaging (MRI) to improve the diagnosis of neurological diseases. An accurate and robust standardized hippocampus segmentation method is required for reliable atrophy assessment. The aim of this work was to develop and evaluate an automatic segmentation tool (DeepHarp) for hippocampus delineation according to the ADNI harmonized hippocampal protocol (HarP). DeepHarp utilizes a two-step process. First, the approximate location of the hippocampus is identified in T1-weighted MRI datasets using an atlas-based approach, which is used to crop the images to a region-of-interest (ROI) containing the hippocampus. In the second step, a convolutional neural network trained using datasets with corresponding manual hippocampus annotations is used to segment the hippocampus from the cropped ROI. The proposed method was developed and validated using 107 datasets with manually segmented hippocampi according to the ADNI-HarP standard as well as 114 multi-center datasets of patients with Alzheimer’s disease, mild cognitive impairment, cerebrovascular disease, and healthy controls. Twenty-three independent datasets manually segmented according to the ADNI-HarP protocol were used for testing to assess the accuracy, while an independent test-retest dataset was used to assess precision. The proposed DeepHarp method achieved a mean Dice similarity score of 0.88, which was significantly better than four other established hippocampus segmentation methods used for comparison. At the same time, the proposed method also achieved a high test-retest precision (mean Dice score: 0.95). In conclusion, DeepHarp can automatically segment the hippocampus from T1-weighted MRI datasets according to the ADNI-HarP protocol with high accuracy and robustness, which can aid atrophy measurements in a variety of pathologies.
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Prange-Kiel, Janine, Danuta A. Dudzinski, Felicitas Pröls, Markus Glatzel, Jakob Matschke, and Gabriele M. Rune. "Aromatase Expression in the Hippocampus of AD Patients and 5xFAD Mice." Neural Plasticity 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/9802086.
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Numerous studies show that 17β-estradiol (E2) protects against Alzheimer’s disease (AD) induced neurodegeneration. The E2-synthesizing enzyme aromatase is expressed in healthy hippocampi, but although the hippocampus is severely affected in AD, little is known about the expression of hippocampal aromatase in AD. To better understand the role of hippocampal aromatase in AD, we studied its expression in postmortem material from patients with AD and in a mouse model for AD (5xFAD mice). In human hippocampi, aromatase-immunoreactivity was observed in the vast majority of principal neurons and signal quantification revealed higher expression of aromatase protein in AD patients compared to age- and sex-matched controls. The tissue-specific first exons of aromatase I.f, PII, I.3, and I.6 were detected in hippocampi of controls and AD patients by RT-PCR. In contrast, 3-month-old, female 5xFAD mice showed lower expression of aromatase mRNA and protein (measured by qRT-PCR and semiquantitative immunohistochemistry) than WT controls; no such differences were observed in male mice. Our findings stress the importance of hippocampal aromatase expression in neurodegenerative diseases.
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Komoltsev, Ilia G., Stepan O. Frankevich, Natalia I. Shirobokova, Aleksandra A. Volkova, Mikhail V. Onufriev, Julia V. Moiseeva, Margarita R. Novikova, and Natalia V. Gulyaeva. "Neuroinflammation and Neuronal Loss in the Hippocampus Are Associated with Immediate Posttraumatic Seizures and Corticosterone Elevation in Rats." International Journal of Molecular Sciences 22, no. 11 (May 30, 2021): 5883. http://dx.doi.org/10.3390/ijms22115883.
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Hippocampal damage after traumatic brain injury (TBI) is associated with late posttraumatic conditions, such as depression, cognitive decline and epilepsy. Mechanisms of selective hippocampal damage after TBI are not well understood. In this study, using rat TBI model (lateral fluid percussion cortical injury), we assessed potential association of immediate posttraumatic seizures and changes in corticosterone (CS) levels with neuroinflammation and neuronal cell loss in the hippocampus. Indices of distant hippocampal damage (neurodegeneration and neuroinflammation) were assessed using histological analysis (Nissl staining, Iba-1 immunohistochemical staining) and ELISA (IL-1β and CS) 1, 3, 7 and 14 days after TBI or sham operation in male Wistar rats (n = 146). IL-1β was elevated only in the ipsilateral hippocampus on day 1 after trauma. CS peak was detected on day 3 in blood, the ipsilateral and contralateral hippocampus. Neuronal cell loss in the hippocampus was demonstrated bilaterally; in the ipsilateral hippocampus it started earlier than in the contralateral. Microglial activation was evident in the hippocampus bilaterally on day 7 after TBI. The duration of immediate seizures correlated with CS elevation, levels of IL-1β and neuronal loss in the hippocampus. The data suggest potential association of immediate post-traumatic seizures with CS-dependent neuroinflammation-mediated distant hippocampal damage.
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Zhang, X.-D., L.-R. Zhao, J.-M. Zhou, Y.-Y. Su, J. Ke, Y. Cheng, J.-L. Li, and W. Shen. "Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state fMRI study." Lupus 29, no. 5 (February 19, 2020): 446–54. http://dx.doi.org/10.1177/0961203320908936.
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Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connectivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.
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Williams, Brent L., Mady Hornig, Kavitha Yaddanapudi, and W. Ian Lipkin. "Hippocampal Poly(ADP-Ribose) Polymerase 1 and Caspase 3 Activation in Neonatal Bornavirus Infection." Journal of Virology 82, no. 4 (December 5, 2007): 1748–58. http://dx.doi.org/10.1128/jvi.02014-07.
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ABSTRACT Infection of neonatal rats with Borna disease virus results in a characteristic behavioral syndrome and apoptosis of subsets of neurons in the hippocampus, cerebellum, and cortex (neonatal Borna disease [NBD]). In the NBD rat hippocampus, dentate gyrus granule cells progressively degenerate. Apoptotic loss of granule cells in NBD is associated with accumulation of zinc in degenerating neurons and reduced zinc in granule cell mossy fibers. Excess zinc can trigger poly(ADP-ribose) polymerase 1 (PARP-1) activation, and PARP-1 activation can mediate neuronal death. Here, we evaluate hippocampal PARP-1 mRNA and protein expression levels, activation, and cleavage, as well as apoptosis-inducing factor (AIF) nuclear translocation and executioner caspase 3 activation, in NBD rats. PARP-1 mRNA and protein levels were increased in NBD hippocampi. PARP-1 expression and activity were increased in granule cell neurons and glia with enhanced ribosylation of proteins, including PARP-1 itself. In contrast, levels of poly(ADP-ribose) glycohydrolase mRNA were decreased in NBD hippocampi. PARP-1 cleavage and AIF expression were also increased in astrocytes in NBD hippocampi. Levels of activated caspase 3 protein were increased in NBD hippocampi and localized to nuclei, mossy fibers, and dendrites of granule cell neurons. These results implicate aberrant zinc homeostasis, PARP-1, and caspase 3 activation as contributing factors in hippocampal neurodegeneration in NBD.
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Frey, Surina, Rico Schieweck, Ignasi Forné, Axel Imhof, Tobias Straub, Bastian Popper, and Michael A. Kiebler. "Physical Activity Dynamically Regulates the Hippocampal Proteome along the Dorso-Ventral Axis." International Journal of Molecular Sciences 21, no. 10 (May 15, 2020): 3501. http://dx.doi.org/10.3390/ijms21103501.
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The hippocampus is central for higher cognition and emotions. In patients suffering from neuropsychiatric or neurodegenerative diseases, hippocampal signaling is altered causing cognitive defects. Thus, therapeutic approaches aim at improving cognition by targeting the hippocampus. Enhanced physical activity (EPA) improves cognition in rodents and humans. A systematic screen, however, for expression changes in the hippocampus along the dorso-ventral axis is missing, which is a prerequisite for understanding molecular mechanisms. Here, we exploited label free mass spectrometry to detect proteomic changes in the hippocampus of male mice upon voluntary wheel running. To identify regional differences, we examined dorsal and ventral CA1, CA3 and dentate gyrus hippocampal subregions. We found metabolic enzymes and actin binding proteins, such as RhoA, being upregulated in the hippocampus upon EPA suggesting a coordination between metabolism and cytoskeleton remodeling; two pathways essential for synaptic plasticity. Strikingly, dorsal and ventral hippocampal subregions respond differentially to EPA. Together, our results provide new insight into proteomic adaptations driven by physical activity in mice. In addition, our results suggest that dorsal and ventral hippocampus, as well as hippocampal subregions themselves, contribute differently to this process. Our study therefore provides an important resource for studying hippocampal subregion diversity in response to EPA.
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Isokawa, M. "Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus." Journal of Neurophysiology 75, no. 5 (May 1, 1996): 1901–8. http://dx.doi.org/10.1152/jn.1996.75.5.1901.
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1. Inhibitory postsynaptic currents (IPSCs) were studied in hippocampal dentate granule cells (DGCs) in the pilocarpine model and human temporal lobe epilepsy, with the use of the whole cell patch-clamp recording technique in slice preparations. 2. In the pilocarpine model, hippocampal slices were prepared from rats that were allowed to experience spontaneous seizures for 2 mo. Human hippocampal specimens were obtained from epileptic patients who underwent surgical treatment for medically intractable seizures. 3. IPSCs were generated by single perforant path stimulation and recorded at a membrane potential (Vm) of 0 mV near the reversal potential of glutamate excitatory postsynaptic currents in the voltage-clamp recording. IPSCs were pharmacologically identified as gamma-aminobutyric acid-A (GABAA) IPSCs by 10 microM bicuculline methiodide. 4. During low-frequency stimulation, IPSCs were not different in amplitude among non-seizure-experienced rat hippocampi, human nonsclerotic hippocampi, seizure-experienced rat hippocampi, and human sclerotic hippocampi. In the last two groups of DGCs, current-clamp recordings indicated the presence of prolonged excitatory postsynaptic potentials (EPSPs) mediated by the N-methyl-D-aspartate (NMDA) receptor. 5. High-frequency stimulation, administered at Vm = -30 mV to activate NMDA currents, reduced GABAA IPSC amplitude specifically in seizure-experienced rat hippocampi (t = 2.5, P < 0.03) and human sclerotic hippocampi (t = 7.7, P < 0.01). This reduction was blocked by an NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV) (50 microM). The time for GABAA IPSCs to recover to their original amplitude was also shortened by the application of APV. 6. I conclude that, when intensively activated, NMDA receptor-mediated excitatory transmission may interact with GABAergic synaptic inhibition in DGCs in seizure-experienced hippocampus to transiently reduce GABA(A) receptor-channel function. Such interactions may contribute to give rise to epileptic excitation in chronically seizure-prone hippocampus.
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Mak, Elijah, Silvy Gabel, Li Su, Guy B. Williams, Robert Arnold, Luca Passamonti, Patricia Vazquez Rodríguez, et al. "Multi-modal MRI investigation of volumetric and microstructural changes in the hippocampus and its subfields in mild cognitive impairment, Alzheimer's disease, and dementia with Lewy bodies." International Psychogeriatrics 29, no. 4 (January 16, 2017): 545–55. http://dx.doi.org/10.1017/s1041610216002143.
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ABSTRACTBackground:Volumetric atrophy and microstructural alterations in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in people with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, no study to date has jointly investigated concomitant microstructural and volumetric changes of the hippocampus in dementia with Lewy bodies (DLB).Methods:A total of 84 subjects (23 MCI, 17 DLB, 14 AD, and 30 healthy controls) were recruited for a multi-modal imaging (3T MRI and DTI) study that included neuropsychological evaluation. Freesurfer was used to segment the total hippocampus and delineate its subfields. The hippocampal segmentations were co-registered to the mean diffusivity (MD) and fractional anisotropy (FA) maps obtained from the DTI images.Results:Both AD and MCI groups showed significantly smaller hippocampal volumes compared to DLB and controls, predominantly in the CA1 and subiculum subfields. Compared to controls, hippocampal MD was elevated in AD, but not in MCI. DLB was characterized by both volumetric and microstructural preservation of the hippocampus. In MCI, higher hippocampal MD was associated with greater atrophy of the hippocampus and CA1 region. Hippocampal volume was a stronger predictor of memory scores compared to MD within the MCI group.Conclusions:Through a multi-modal integration, we report novel evidence that the hippocampus in DLB is characterized by both macrostructural and microstructural preservation. Contrary to recent suggestions, our findings do not support the view that DTI measurements of the hippocampus are superior to volumetric changes in characterizing group differences, particularly between MCI and controls.
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Schang, Anne-Laure, Valérie Ngô-Muller, Christian Bleux, Anne Granger, Marie-Claude Chenut, Catherine Loudes, Solange Magre, Raymond Counis, Joëlle Cohen-Tannoudji, and Jean-Noël Laverrière. "GnRH Receptor Gene Expression in the Developing Rat Hippocampus: Transcriptional Regulation and Potential Roles in Neuronal Plasticity." Endocrinology 152, no. 2 (December 1, 2010): 568–80. http://dx.doi.org/10.1210/en.2010-0840.
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Abstract In the pituitary of mammals, the GnRH receptor (GnRHR) plays a primary role in the control of reproductive function. It is further expressed in the hippocampus, where its function, however, is not well defined. By quantitative RT-PCR analyses, we demonstrate herein that the onset of GnRHR gene (Gnrhr) expression in the rat hippocampus was unexpectedly delayed as compared to the pituitary and only occurred after birth. Using a previously described transgenic mouse model bearing the human placental alkaline phosphatase reporter gene under the control of the rat Gnrhr promoter, we established a positive correlation between the temporal pattern of Gnrhr mRNA levels and promoter activity in the hippocampal formation. The gradual appearance of human placental alkaline phosphatase transgene expression occurred simultaneously in the hippocampus and interconnected structures such as the lateral septum and the amygdala, coinciding with the establishment of hippocampo-septal projections. Analysis of transcription factors together with transient transfection assays in hippocampal neurons indicated that the combinatorial code governing the hippocampus-specific expression of the Gnrhr is distinct from the pituitary, likely involving transactivating factors such as NUR77, cyclic AMP response element binding protein, and Finkel-Biskis-Jinkins murine osteosarcoma virus oncogene homolog. A silencing transcription factor acting via the -3255/-1135 promoter region of the Gnrhr may be responsible for the transcriptional repression observed around birth. Finally, GnRH directly stimulated via activation of its receptor the expression of several marker genes of neuronal plasticity such as Egr1, synaptophysin, and spinophilin in hippocampal primary cultures, suggesting a role for GnRHR in neuronal plasticity. Further characterization of these mechanisms may help unravel important functions of GnRH/GnRHR signaling in the brain.
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Umeoka, Shuichi C., Hans O. Lüders, John P. Turnbull, Mohamad Z. Koubeissi, and Robert J. Maciunas. "Requirement of longitudinal synchrony of epileptiform discharges in the hippocampus for seizure generation: a pilot study." Journal of Neurosurgery 116, no. 3 (March 2012): 513–24. http://dx.doi.org/10.3171/2011.10.jns11261.
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Object The goal in this study was to assess the role of longitudinal hippocampal circuits in the generation of interictal and ictal activity in temporal lobe epilepsy (TLE) and to evaluate the effects of multiple hippocampal transections (MHT). Methods In 6 patients with TLE, the authors evaluated the synchrony of hippocampal interictal and ictal epileptiform discharges by using a cross-correlation analysis, and the effect of MHT on hippocampal interictal spikes was studied. Five of the 6 patients were studied with depth electrodes, and epilepsy surgery was performed in 4 patients (anterior temporal lobectomy in 1 and MHT in 3). Results Four hundred eighty-two (95.1%) of 507 hippocampal spikes showed an anterior-to-posterior propagation within the hippocampus, with a fixed peak-to-peak interval. During seizures, a significant increase of synchronization between different hippocampal regions and between the hippocampus and the ipsilateral anterior parahippocampal gyrus was observed in all seizures. An ictal increase in synchronization between the hippocampus and ipsilateral amygdala was seen in only 24.1% of the seizures. No changes in synchronization were noticed during seizures between the hippocampi and the amygdalae on either side. The structure leading the epileptic seizures varied over time during a given seizure and also from one seizure to another. Spike analysis during MHT demonstrated that there were two spike populations that reacted differently to this procedure—namely, 1) spikes that showed maximum amplitude at the head of the hippocampus (type H); and 2) spikes that showed the highest amplitude at the hippocampal body (type B). A striking decrease in amplitude and frequency of type B spikes was noticed in all 3 patients after transections at the head or anterior portion of the hippocampal body. Type H spikes were seen in 2 cases and did not change in amplitude and frequency throughout MHT. Type B spikes showed constantly high cross-correlation values in different derivations and a relatively fixed peak-to-peak interval before MHT. This fixed interpeak delay disappeared after the first transection, although high cross-correlation values persisted unchanged. All patients who underwent MHT remained seizure free for more than 2 years. Conclusions These data suggest that synchronized discharges involving the complete anterior-posterior axis of the hippocampal/parahippocampal (H/P) formation underlie the spread of epileptiform discharges outside the H/P structures and, therefore, for the generation of epileptic seizures originating in the H/P structures. This conclusion is supported by the following observations. 1) Hippocampal spikes are consistently synchronized in the whole hippocampal structures, with a fixed delay between the different hippocampal areas. 2) One or two transections between the head and body of the hippocampal formation are sufficient to abolish hippocampal spikes that are synchronized along the anterior-posterior axis of the hippocampus. 3) Treatment with MHT leads to seizure freedom in patients with H/P epilepsy.
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Comber, David B., E. Bryn Pitt, Hunter B. Gilbert, Matthew W. Powelson, Emily Matijevich, Joseph S. Neimat, Robert J. Webster, and Eric J. Barth. "Optimization of Curvilinear Needle Trajectories for Transforamenal Hippocampotomy." Operative Neurosurgery 13, no. 1 (July 25, 2016): 15–22. http://dx.doi.org/10.1227/neu.0000000000001361.
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Abstract BACKGROUND: The recently developed magnetic resonance imaging–guided laser-induced thermal therapy offers a minimally invasive alternative to craniotomies performed for tumor resection or for amygdalohippocampectomy to control seizure disorders. Current laser-induced thermal therapies rely on linear stereotactic trajectories that mandate twist-drill entry into the skull and potentially long approaches traversing healthy brain. The use of robotically driven, telescoping, curved needles has the potential to reduce procedure invasiveness by tailoring trajectories to the curved shape of the ablated structure and by enabling access through natural orifices. OBJECTIVE: To investigate the feasibility of using a concentric tube robot to access the hippocampus through the foramen ovale to deliver thermal therapy and thereby provide a percutaneous treatment for epilepsy without drilling the skull. METHODS: The skull and both hippocampi were segmented from dual computed tomography/magnetic resonance image volumes for 10 patients. For each of the 20 hippocampi, a concentric tube robot was designed and optimized to traverse a trajectory from the foramen ovale to and through the hippocampus from head to tail. RESULTS: Across all 20 cases, the mean distances (errors) between the hippocampus medial axis and backbone of the needle were 0.55, 1.11, and 1.66 mm for the best, mean, and worst case, respectively. CONCLUSION: These curvilinear trajectories would provide accurate transforamenal delivery of an ablation probe to typical hippocampus volumes. This strategy has the potential both to decrease the invasiveness of the procedure and to increase the completeness of hippocampal ablation.
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Gervitz, L. M., L. O. Lutherer, D. G. Davies, J. H. Pirch, and J. C. Fowler. "Adenosine induces initial hypoxic-ischemic depression of synaptic transmission in the rat hippocampus in vivo." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 280, no. 3 (March 1, 2001): R639—R645. http://dx.doi.org/10.1152/ajpregu.2001.280.3.r639.
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The present study was designed to investigate the role of adenosine in the hypoxic depression of synaptic transmission in rat hippocampus. An in vivo model of hypoxic synaptic depression was developed in which the common carotid artery was occluded on one side in the urethane-anesthetized rat. Inspired oxygen levels were controlled through a tracheal cannula. Rats were placed in a stereotaxic apparatus for stimulation and recording of bilateral hippocampal field excitatory postsynaptic potentials. The percent inspired oxygen could be reduced to levels that produced a reversible and repeatable depression of evoked synaptic transmission restricted to the hippocampus ipsilateral to the occlusion. Further reduction in the level of inspired oxygen depressed synaptic transmission recorded from both hippocampi. The adenosine nonselective antagonist caffeine and the A1selective antagonist 8-cyclopentyltheophylline prevented the initial depression in synaptic transmission. We conclude that the initial depression of synaptic transmission observed in the rat hippocampus in vivo is due to endogenous adenosine acting at neuronal adenosine A1 receptors.
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Shen, Renrui. "How Fructose Affects the Hippocampus." Journal of Clinical Medicine Research 3, no. 3 (September 24, 2022): 98. http://dx.doi.org/10.32629/jcmr.v3i3.951.
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This review explores the effects of fructose on the hippocampus: hippocampal function and structure, hippocampal neurogenesis, and hippocampal cognitive function. First, this result confirms that excess fructose intake affects the microstructure of pathways connecting the hippocampus to other brain areas. Fructose has the potential to affect neurogenesis in the hippocampus, and a diet high in fructose can impair learning and memory, leading to cognitive impairment. However, further research is needed to apply animal experiments to humans in the future. The literature review focused on the effects of fructose, but a balanced intake of other nutrients also needed to be considered.
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Mao, Dun, Adam R. Neumann, Jianjun Sun, Vincent Bonin, Majid H. Mohajerani, and Bruce L. McNaughton. "Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex." Proceedings of the National Academy of Sciences 115, no. 31 (July 16, 2018): 8015–18. http://dx.doi.org/10.1073/pnas.1803224115.
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Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex.
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Omer Taha Ahmed Elmukashfi. "Elmukashfi’s Protocol for Hippocampal Volumetry among Sudanese attending Elmoalem Hospital: Structural MRI Study; Sudan; 2022." World Journal of Advanced Research and Reviews 20, no. 2 (November 30, 2023): 953–59. http://dx.doi.org/10.30574/wjarr.2023.20.2.2222.
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There is a relation between many neuropsychiatric disorders and reduction in hippocampal volume. So, a protocol for researches in this area is highly needed. Study aimed to design and validate a protocol for hippocampal volumetry to facilitate manual segmentation of hippocampus region. It was a comparative study, carried at Diagnostic Imaging Clinic at Elmoalem Hospital; where 65 Sudanese individuals were surveyed in period (December 2021 –April 2022). Data was collected through master sheet for sociodemographic information, 3D magnetic resonance imaging for measuring hippocampus volume, and imaging acquisition. Software for measurements 3D slicer version (4.11) was used, where hippocampus is mapped by delineating its boundaries. Protocol was composed of mapping hippocampus. Mapping hippocampus: identify sagittal view, lateral fissure, temporal horn of lateral ventricle, hippocampus region, temporal and occipital horn of lateral ventricle, choroid plexus of lateral ventricle. Among these slides hippocampus has been delineated. Statistical Computing: Data was analyzed using SPSS version 23. Reliability test was performed by obtaining Cronbach’s alpha. Protocol considered reliable if value of Cronbach’s alpha is close to (+1). P-value ≤ 0.05 was considered statistically significant. Validation of Protocol: Calculation of hippocampus volume is valid as total volume correlates strongly with both right and left measurements (correlation coefficient 0.76 and 0.87 respectively and p-value <0.001). Reliability test was 0.85; which was close to (+1). Conclusion and recommendation: This protocol represents a valid, reliable, and applicable method for measuring hippocampal volume. It could be a step to develop an international standard protocol for hippocampal volumetry.
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King, R., D. Jecmen, A. Alkozei, A. C. Raikes, M. A. Grandner, and W. D. Killgore. "0082 Hippocampal Gray Matter Volume in Healthy Adult Population is Associated with Habitual Sleep Duration." Sleep 43, Supplement_1 (April 2020): A33—A34. http://dx.doi.org/10.1093/sleep/zsaa056.080.
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Abstract Introduction The hippocampus is well known for its role in sleep and memory consolidation in adolescents, and has been shown to demonstrate neural plasticity and neuronal regeneration. However, the relationship between sleep and hippocampal gray matter volume in healthy adults remains to be fully characterized. We hypothesized that total sleep time (TST), as measured by actigraphy, would correlate positively with gray matter volume (GMV) in the hippocampus, a key memory region of the brain. Methods Forty-five healthy normal sleeping adults between 20–45 years of age wore an actigraph for seven days to quantify habitual sleep duration and underwent magnetic resonance imaging during the actigraphy period. Voxel based morphometry in SPM12 was used to estimate GMV at the whole brain level. A region-of-interest mask was used to constrain data analysis to the left and right hippocampi. Results Habitual sleep duration per night correlated positively with gray matter volume within part of the left hippocampus (x=-36,y=-20,z=-18; k=32, pFWE-corr=0.093), controlling for age, sex, total intracranial volume, intelligence scores and mood. No correlation was found between TST and hippocampal GMV in the right hippocampus. Conclusion Longer sleep time was associated with greater gray matter volume in the left hippocampus. This finding is consistent with what has been observed in healthy children and extend these findings to healthy normal sleeping adults. While TST and GMV are correlated, the causal association cannot be established here. Further research may explore the effects of sleep extension on GMV and how these volume differences associate with various aspects of cognition, particularly memory. It should be noted that this study only included healthy adults with sleep durations between 6–9 hours per night. Future studies would benefit from including adults with a greater variance in their sleep patterns to better understand the relationship between sleep and hippocampal volume, and its potential effects on memory performance. Support Defense Advanced Research Projects Agency Young Faculty Award: DARPA-12-12-11-YFA11-FP-029
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Covington, Natalie V., Sarah Brown-Schmidt, and Melissa C. Duff. "The Necessity of the Hippocampus for Statistical Learning." Journal of Cognitive Neuroscience 30, no. 5 (May 2018): 680–97. http://dx.doi.org/10.1162/jocn_a_01228.
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Converging evidence points to a role for the hippocampus in statistical learning, but open questions about its necessity remain. Evidence for necessity comes from Schapiro and colleagues who report that a single patient with damage to hippocampus and broader medial temporal lobe cortex was unable to discriminate new from old sequences in several statistical learning tasks. The aim of the current study was to replicate these methods in a larger group of patients who have either damage localized to hippocampus or broader medial temporal lobe damage, to ascertain the necessity of the hippocampus in statistical learning. Patients with hippocampal damage consistently showed less learning overall compared with healthy comparison participants, consistent with an emerging consensus for hippocampal contributions to statistical learning. Interestingly, lesion size did not reliably predict performance. However, patients with hippocampal damage were not uniformly at chance and demonstrated above-chance performance in some task variants. These results suggest that hippocampus is necessary for statistical learning levels achieved by most healthy comparison participants but significant hippocampal pathology alone does not abolish such learning.
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Sanda, Pavel, Paola Malerba, Xi Jiang, Giri P. Krishnan, Jorge Gonzalez-Martinez, Eric Halgren, and Maxim Bazhenov. "Bidirectional Interaction of Hippocampal Ripples and Cortical Slow Waves Leads to Coordinated Spiking Activity During NREM Sleep." Cerebral Cortex 31, no. 1 (September 30, 2020): 324–40. http://dx.doi.org/10.1093/cercor/bhaa228.
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Abstract The dialogue between cortex and hippocampus is known to be crucial for sleep-dependent memory consolidation. During slow wave sleep, memory replay depends on slow oscillation (SO) and spindles in the (neo)cortex and sharp wave-ripples (SWRs) in the hippocampus. The mechanisms underlying interaction of these rhythms are poorly understood. We examined the interaction between cortical SO and hippocampal SWRs in a model of the hippocampo–cortico–thalamic network and compared the results with human intracranial recordings during sleep. We observed that ripple occurrence peaked following the onset of an Up-state of SO and that cortical input to hippocampus was crucial to maintain this relationship. A small fraction of ripples occurred during the Down-state and controlled initiation of the next Up-state. We observed that the effect of ripple depends on its precise timing, which supports the idea that ripples occurring at different phases of SO might serve different functions, particularly in the context of encoding the new and reactivation of the old memories during memory consolidation. The study revealed complex bidirectional interaction of SWRs and SO in which early hippocampal ripples influence transitions to Up-state, while cortical Up-states control occurrence of the later ripples, which in turn influence transition to Down-state.
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Sherry, David F., and Jennifer S. Hoshooley. "Seasonal hippocampal plasticity in food-storing birds." Philosophical Transactions of the Royal Society B: Biological Sciences 365, no. 1542 (March 27, 2010): 933–43. http://dx.doi.org/10.1098/rstb.2009.0220.
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Both food-storing behaviour and the hippocampus change annually in food-storing birds. Food storing increases substantially in autumn and winter in chickadees and tits, jays and nutcrackers and nuthatches. The total size of the chickadee hippocampus increases in autumn and winter as does the rate of hippocampal neurogenesis. The hippocampus is necessary for accurate cache retrieval in food-storing birds and is much larger in food-storing birds than in non-storing passerines. It therefore seems probable that seasonal change in caching and seasonal change in the hippocampus are causally related. The peak in recruitment of new neurons into the hippocampus occurs before birds have completed food storing and cache retrieval for the year and may therefore be associated with spacing caches, encoding the spatial locations of caches, or creating a neuronal architecture involved in the recollection of cache sites. The factors controlling hippocampal plasticity in food-storing birds are not well understood. Photoperiodic manipulations that produce change in food-storing behaviour have no effect on either hippocampal size or neuronal recruitment. Available evidence suggests that changes in hippocampal size and neurogenesis may be a consequence of the behavioural and cognitive involvement of the hippocampus in storing and retrieving food.
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Appelt, D. M., G. C. Kopen, L. J. Boyne, and B. J. Balin. "Localization of transglutaminase in hippocampal neurons: implications for Alzheimer's disease." Journal of Histochemistry & Cytochemistry 44, no. 12 (December 1996): 1421–27. http://dx.doi.org/10.1177/44.12.8985134.
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The purpose of this investigation was to identify and localize tissue transglutaminase (TGase) within neurons from the hippocampi of normal aged individuals and of those with confirmed Alzheimer's disease (AD). This enzyme may be a factor in the molecular mechanisms of neurodegeneration and formation of insoluble macromolecular complexes found in the neurons of normal aged and AD brain tissue. An antibody made to the extracellular TGase, coagulation factor XIIIa, was found to be specific for purified intracellular guinea pig liver tissue TGase. The specificity for liver tissue TGase has enabled us to identify tissue TGase(s) within rat hippocampal neurons and within neurons from normal aged and AD hippocampal tissues. Degenerating neurons from the AD hippocampus, compared to neurons from the normal aged hippocampus, exhibited increased immunoreactivity for TGase and demonstrated co-labeling for PHF1 and anti-TGase. Our results suggest that TGase may be associated with the neurofibrillary degeneration observed in AD, thereby implicating TGase as a potential factor in the pathogenesis of Alzheimer's disease.
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Grochowski, Cezary, Kamil Jonak, Marcin Maciejewski, Andrzej Stępniewski, and Mansur Rahnama-Hezavah. "Alteration within the Hippocampal Volume in Patients with LHON Disease—7 Tesla MRI Study." Journal of Clinical Medicine 10, no. 1 (December 23, 2020): 14. http://dx.doi.org/10.3390/jcm10010014.
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Purpose: The aim of this study was to assess the volumetry of the hippocampus in the Leber’s hereditary optic neuropathy (LHON) of blind patients. Methods: A total of 25 patients with LHON were randomly included into the study from the national health database. A total of 15 patients were selected according to the inclusion criteria. The submillimeter segmentation of the hippocampus was based on three-dimensional spoiled gradient recalled acquisition in steady state (3D-SPGR) BRAVO 7T magnetic resonance imaging (MRI) protocol. Results: Statistical analysis revealed that compared to healthy controls (HC), LHON subjects had multiple significant differences only in the right hippocampus, including a significantly higher volume of hippocampal tail (p = 0.009), subiculum body (p = 0.018), CA1 body (p = 0.002), hippocampal fissure (p = 0.046), molecular layer hippocampus (HP) body (p = 0.014), CA3 body (p = 0.006), Granule Cell (GC) and Molecular Layer (ML) of the Dentate Gyrus (DG)–GC ML DG body (p = 0.003), CA4 body (p = 0.001), whole hippocampal body (p = 0.018), and the whole hippocampus volume (p = 0.023). Discussion: The ultra-high-field magnetic resonance imaging allowed hippocampus quality visualization and analysis, serving as a powerful in vivo diagnostic tool in the diagnostic process and LHON disease course assessment. The study confirmed previous reports regarding volumetry of hippocampus in blind individuals.
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Nasser, Soraya, Moulkheir Naoui, Ghalem Belalem, and Saïd Mahmoudi. "Semantic Segmentation of Hippocampal Subregions With U-Net Architecture." International Journal of E-Health and Medical Communications 12, no. 6 (November 2021): 1–20. http://dx.doi.org/10.4018/ijehmc.20211101.oa4.
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The Automatic semantic segmentation of the hippocampus is an important area of research in which several convolutional neural networks (CNN) models have been used to detect the hippocampus from whole cerebral MRI. In this paper we present two convolutional neural networks the first network ( Hippocampus Segmentation Single Entity HSSE) segmented the hippocampus as a single entity and the second used to detect the hippocampal sub-regions ( Hippocampus Segmentation Multi Class HSMC), these two networks inspire their architecture of the U-net model. Two cohorts were used as training data from (NITRC) (NeuroImaging Tools & Resources Collaboratory (NITRC)) annotated by ITK-SNAP software. We analyze this networks alongside other recent methods that do hippocampal segmentation, the results obtained are encouraging and reach dice scores greater than 0.84
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Tang, Mufeng, Tommaso Salvatori, Beren Millidge, Yuhang Song, Thomas Lukasiewicz, and Rafal Bogacz. "Recurrent predictive coding models for associative memory employing covariance learning." PLOS Computational Biology 19, no. 4 (April 14, 2023): e1010719. http://dx.doi.org/10.1371/journal.pcbi.1010719.
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The computational principles adopted by the hippocampus in associative memory (AM) tasks have been one of the most studied topics in computational and theoretical neuroscience. Recent theories suggested that AM and the predictive activities of the hippocampus could be described within a unitary account, and that predictive coding underlies the computations supporting AM in the hippocampus. Following this theory, a computational model based on classical hierarchical predictive networks was proposed and was shown to perform well in various AM tasks. However, this fully hierarchical model did not incorporate recurrent connections, an architectural component of the CA3 region of the hippocampus that is crucial for AM. This makes the structure of the model inconsistent with the known connectivity of CA3 and classical recurrent models such as Hopfield Networks, which learn the covariance of inputs through their recurrent connections to perform AM. Earlier PC models that learn the covariance information of inputs explicitly via recurrent connections seem to be a solution to these issues. Here, we show that although these models can perform AM, they do it in an implausible and numerically unstable way. Instead, we propose alternatives to these earlier covariance-learning predictive coding networks, which learn the covariance information implicitly and plausibly, and can use dendritic structures to encode prediction errors. We show analytically that our proposed models are perfectly equivalent to the earlier predictive coding model learning covariance explicitly, and encounter no numerical issues when performing AM tasks in practice. We further show that our models can be combined with hierarchical predictive coding networks to model the hippocampo-neocortical interactions. Our models provide a biologically plausible approach to modelling the hippocampal network, pointing to a potential computational mechanism during hippocampal memory formation and recall, which employs both predictive coding and covariance learning based on the recurrent network structure of the hippocampus.
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Haam, Juhee, Jingheng Zhou, Guohong Cui, and Jerrel L. Yakel. "Septal cholinergic neurons gate hippocampal output to entorhinal cortex via oriens lacunosum moleculare interneurons." Proceedings of the National Academy of Sciences 115, no. 8 (February 7, 2018): E1886—E1895. http://dx.doi.org/10.1073/pnas.1712538115.
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Neuromodulation of neural networks, whereby a selected circuit is regulated by a particular modulator, plays a critical role in learning and memory. Among neuromodulators, acetylcholine (ACh) plays a critical role in hippocampus-dependent memory and has been shown to modulate neuronal circuits in the hippocampus. However, it has remained unknown how ACh modulates hippocampal output. Here, using in vitro and in vivo approaches, we show that ACh, by activating oriens lacunosum moleculare (OLM) interneurons and therefore augmenting the negative-feedback regulation to the CA1 pyramidal neurons, suppresses the circuit from the hippocampal area CA1 to the deep-layer entorhinal cortex (EC). We also demonstrate, using mouse behavior studies, that the ablation of OLM interneurons specifically impairs hippocampus-dependent but not hippocampus-independent learning. These data suggest that ACh plays an important role in regulating hippocampal output to the EC by activating OLM interneurons, which is critical for the formation of hippocampus-dependent memory.
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Konopka-Filippow, Monika, Ewa Sierko, Dominika Hempel, Rafał Maksim, Natalia Samołyk-Kogaczewska, Tomasz Filipowski, Ewa Rożkowska, et al. "The Learning Curve and Inter-Observer Variability in Contouring the Hippocampus under the Hippocampal Sparing Guidelines of Radiation Therapy Oncology Group 0933." Current Oncology 29, no. 4 (April 8, 2022): 2564–74. http://dx.doi.org/10.3390/curroncol29040210.
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Hippocampal-sparing brain radiotherapy (HS-BRT) in cancer patients results in preservation of neurocognitive function after brain RT which can contribute to patients’ quality of life (QoL). The crucial element in HS-BRT treatment planning is appropriate contouring of the hippocampus. Ten doctors delineated the left and right hippocampus (LH and RH, respectively) on 10 patients’ virtual axial images of brain CT fused with T1-enhanced MRI (1 mm) according to the RTOG 0933 atlas recommendations. Variations in the spatial localization of the structure were described in three directions: right–left (X), cranio-caudal (Y), and forward–backward (Z). Discrepancies concerned three-dimensional localization, shape, volume and size of the hippocampus. The largest differences were observed in the first three delineated cases which were characterized by larger hippocampal volumes than the remaining seven cases. The volumes of LH of more than half of hippocampus contours were marginally bigger than those of RH. Most differences in delineation of the hippocampus were observed in the area of the posterior horn of the lateral ventricle. Conversely, a large number of hippocampal contours overlapped near the brainstem and the anterior horn of the lateral ventricle. The most problematic area of hippocampal contouring is the posterior horn of the lateral ventricle. Training in the manual contouring of the hippocampus during HS-BRT treatment planning under the supervision of experienced radiation oncologists is necessary to achieve optimal outcomes. This would result in superior outcomes of HS-BRT treatment and improvement in QoL of patients compared to without HS-BRT procedure. Correct delineation of the hippocampus is problematic. This study demonstrates difficulties in HS-BRT treatment planning and highlights critical points during hippocampus delineation.
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Bingman, Verner P., and Rubén N. Muzio. "Reflections on the Structural-Functional Evolution of the Hippocampus: What Is the Big Deal about a Dentate Gyrus." Brain, Behavior and Evolution 90, no. 1 (2017): 53–61. http://dx.doi.org/10.1159/000475592.
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The vertebrate hippocampal formation has been central in discussions of comparative cognition, nurturing an interest in understanding the evolution of variation in hippocampal organization among vertebrate taxa and the functional consequences of that variation. Assuming some similarity between the medial pallium of extant amphibians and the hippocampus of stem tetrapods, we propose the hypothesis that the hippocampus of modern amniotes began with a medial pallium characterized by a relatively undifferentiated cytoarchitecture, more direct thalamic and olfactory sensory inputs, and a broad role in associative learning and memory processes that nonetheless included the map-like representation of space. From this modest beginning evolved the cognitively more specialized hippocampal formation of birds and the hippocampus of mammals with its confounding dentate gyrus. Much has been made of trying to identify a dentate homologue in birds, but there are compelling reasons to believe no such structural homologue/functional equivalent exists. The uniqueness of the mammalian dentate then raises the question of what might be the functional consequences of a hippocampus with a dentate compared to one without. One might be tempted to speculate that the presence of a dentate gyrus facilitates so-called pattern separation, but birds with their suspected dentate-less hippocampus display excellent hippocampal-dependent pattern separation relying on space. Perhaps one consequence of a dentate is a hippocampus better designed to process a broader array of stimuli beyond space to more robustly support episodic memory. What is clear is that any meaningful reconstruction of hippocampal evolution and the eventual identification of any subdivisional homologies will require more data on the neurobiological and functional properties of the nonmammalian hippocampus, particularly those of amphibians and reptiles.
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Giribabu, Nelli, Nelli Srinivasarao, Somesula Swapna Rekha, Sekaran Muniandy, and Naguib Salleh. "Centella asiaticaAttenuates Diabetes Induced Hippocampal Changes in Experimental Diabetic Rats." Evidence-Based Complementary and Alternative Medicine 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/592062.
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Diabetes mellitus has been reported to affect functions of the hippocampus. We hypothesized thatCentella asiatica, a herb traditionally being used to improve memory, prevents diabetes-related hippocampal dysfunction. Therefore, the aim of this study was to investigate the protective role ofC. asiaticaon the hippocampus in diabetes.Methods. Streptozotocin- (STZ-) induced adult male diabetic rats received 100 and 200 mg/kg/day body weight (b.w)C. asiaticaleaf aqueous extract for four consecutive weeks. Following sacrifice, hippocampus was removed and hippocampal tissue homogenates were analyzed for Na+/K+-, Ca2+- and Mg2+-ATPases activity levels. Levels of the markers of inflammation (tumor necrosis factor, TNF-α; interleukin, IL-6; and interleukin, IL-1β) and oxidative stress (lipid peroxidation product: LPO, superoxide dismutase: SOD, catalase: CAT, and glutathione peroxidase: GPx) were determined. The hippocampal sections were visualized for histopathological changes.Results. Administration ofC. asiaticaleaf aqueous extract to diabetic rats maintained near normal ATPases activity levels and prevents the increase in the levels of inflammatory and oxidative stress markers in the hippocampus. Lesser signs of histopathological changes were observed in the hippocampus ofC. asiaticaleaf aqueous extract treated diabetic rats.Conclusions.C. asiaticaleaf protects the hippocampus against diabetes-induced dysfunction which could help to preserve memory in this condition.
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Hojo, Yasushi, Shimpei Higo, Hirotaka Ishii, Yuuki Ooishi, Hideo Mukai, Gen Murakami, Toshihiro Kominami, et al. "Comparison between Hippocampus-Synthesized and Circulation-Derived Sex Steroids in the Hippocampus." Endocrinology 150, no. 11 (July 9, 2009): 5106–12. http://dx.doi.org/10.1210/en.2009-0305.
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Estradiol (E2) and other sex steroids play essential roles in the modulation of synaptic plasticity and neuroprotection in the hippocampus. To clarify the mechanisms for these events, it is important to determine the respective role of circulating vs. locally produced sex steroids in the male hippocampus. Liquid chromatography-tandem mass spectrometry in combination with novel derivatization was employed to determine the concentration of sex steroids in adult male rat hippocampus. The hippocampal levels of 17β-E2, testosterone (T), and dihydrotestosterone (DHT) were 8.4, 16.9, and 6.6 nm, respectively, and these levels were significantly higher than circulating levels. The hippocampal estrone (E1) level was, in contrast, very low around 0.015 nm. After castration to deplete circulating high level T, hippocampal levels of T and DHT decreased considerably to 18 and 3%, respectively, whereas E2 level only slightly decreased to 83%. The strong reduction in hippocampal DHT resulting from castration implies that circulating T may be a main origin of DHT. In combination with results obtained from metabolism analysis of [3H]steroids, we suggest that male hippocampal E2 synthesis pathway may be androstenedione → T → E2 or dehydroepiandrosterone → androstenediol → T → E2 but not androstenedione → E1 → E2.
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Rutecki, Paul A., Robert G. Grossman, Dawna Armstrong, and Susan Irish-Loewen. "Electrophysiological connections between the hippocampus and entorhinal cortex in patients with complex partial seizures." Journal of Neurosurgery 70, no. 5 (May 1989): 667–75. http://dx.doi.org/10.3171/jns.1989.70.5.0667.
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✓ The electrophysiological properties of the neural pathways between the hippocampus and the entorhinal cortex were studied intraoperatively in 31 patients undergoing anterior temporal lobectomy for medically intractable complex partial seizures. The hippocampus, removed en bloc, was studied histologically and the pathology was correlated with the electrophysiological findings. In 29 of the patients, entorhinal stimulation evoked a characteristic positive-negative potential in the hippocampus. The entorhinal-evoked hippocampal response closely resembled, or was identical to, the spontaneously occurring hippocampal interictal spike discharge. In patients with Ammon's horn sclerosis in whom there was a major loss of neurons in the hippocampal subfields CA1, CA3, and CA4, the evoked responses were of simple morphology and long latency(mean 21.9 msec to the peak of the first potential). In patients with a ganglioglioma in whom the hippocampus was histologically normal, the evoked responses were of greater complexity and shorter latency (mean 11.8 msec). Stimulation at a single entorhinal site evoked similar waveforms at different hippocampal recording sites. Conversely, stimulation at different entorhinal sites evoked similar responses at a single hippocampal recording site. Stimulation of the hippocampus evoked a potential in the entorhinal cortex and, in some instances, in the amygdala, insula, and lateral temporal cortex. These connections may produce a positive feedback loop that favors seizure generation.
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He, Bing Song, Xue Ping Zhang, and Yong Gang Shi. "Hippocampus Segmentation Techniques: A Survey." Advanced Materials Research 760-762 (September 2013): 2086–90. http://dx.doi.org/10.4028/www.scientific.net/amr.760-762.2086.
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Since the volume of hippocampal formation has been found to be an early biomarker for MCI and Alzheimer's disease, hippocampus segmentation plays a significant role in clinical diagnosis. Because hippocampus in MR images presents features of low contrast, low signal-to-noise ratio and discontinuous boundaries, accurate segmentation still remains a challenging task. We presented a survey of the methods used to segment the hippocampal formation in MR images of human brain and concluded with a discussion on the trend of the future research in hippocampus segmentation.
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Khalilov, I., A. Gainutdinov, and R. Khazipov. "BILATERAL SYNCHRONIZATION OF HIPPOCAMPAL THETA-OSCILLATIONS <i>IN VITRO</i>." Журнал эволюционной биохимии и физиологии 59, no. 3 (May 1, 2023): 207–14. http://dx.doi.org/10.31857/s004445292303004x.
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Hippocampal theta oscillations are pivotal for hippocampal functions of spatial navigation, learning and memory. In the behaving animals in vivo, hippocampal theta oscillations display bilateral synchronization. Internally generated oscillations in the theta frequency range have also been described in the intact hippocampus preparation in vitro. How theta oscillations are synchronized between the left and right hippocampi remains elusive, however. We used preparation of the intact hippocampi interconnected by the ventral hippocampal commissure prepared from juvenile and adult mice and rats in vitro. Local field potentials and multiunit activity were recorded using extracellular electrodes from the pyramidal cell layer and stratum radiatum of the left and right hippocampi. Neuronal network activity in the left and right hippocampi was organized in theta oscillations, which strongly modulated neuronal firing of CA1 neurons. Both neuronal activity and field potential theta oscillations showed high levels of bilateral synchronization. Theta oscillations persisted on both sides, but their bilateral synchronization was eliminated after surgical cut of the ventral hippocampal commissure. Thus, theta oscillations are synchronized in the left and right hippocampi in vitro, and their bilateral synchronization is provided by the ventral commissural connections.
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Nelson, Michael D., and Alecia M. Tumpap. "Posttraumatic stress disorder symptom severity is associated with left hippocampal volume reduction: a meta-analytic study." CNS Spectrums 22, no. 4 (December 19, 2016): 363–72. http://dx.doi.org/10.1017/s1092852916000833.
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ObjectiveMany studies have reported hippocampal volume reductions associated with posttraumatic stress disorder (PTSD), while others have not. Here we provide an updated meta-analysis of such reductions associated with PTSD and evaluate the association between symptom severity and hippocampal volume.MethodsA total of 37 studies met the criteria for inclusion in the meta-analysis. Mean effect sizes (Hedges’ g) and 95% confidence intervals (CI95%) were computed for each study and then averaged to obtain an overall mean effect size across studies. Meta-regression was employed to examine the relationship between PTSD symptom severity and hippocampal volume.ResultsResults showed that PTSD is associated with significant bilateral reduction of the hippocampus (left hippocampus effect size=–0.400, p<0.001, 5.24% reduction; right hippocampus effect size=–0.462, p<0.001, 5.23% reduction). Symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS), was significantly associated with decreased left, but not right, hippocampal volume.ConclusionsPTSD was associated with significant bilateral volume reduction of the hippocampus. Increased symptom severity was significantly associated with reduced left hippocampal volume. This finding is consistent with the hypothesis that PTSD is more neurotoxic to the left hippocampus than to the right. However, whether the association between PTSD and lower hippocampal volume reflects a consequence of or a predisposition to PTSD remains unclear. More prospective studies are needed in this area.