Physical exercise prevents stress-induced activation of granule neurons and enhances local inhibitory mechanisms in the dentate gyrus.

PubMed

Schoenfeld, Timothy J; Rada, Pedro; Pieruzzini, Pedro R; Hsueh, Brian; Gould, Elizabeth

2013-05-01

Physical exercise is known to reduce anxiety. The ventral hippocampus has been linked to anxiety regulation but the effects of running on this subregion of the hippocampus have been incompletely explored. Here, we investigated the effects of cold water stress on the hippocampus of sedentary and runner mice and found that while stress increases expression of the protein products of the immediate early genes c-fos and arc in new and mature granule neurons in sedentary mice, it has no such effect in runners. We further showed that running enhances local inhibitory mechanisms in the hippocampus, including increases in stress-induced activation of hippocampal interneurons, expression of vesicular GABA transporter (vGAT), and extracellular GABA release during cold water swim stress. Finally, blocking GABAA receptors in the ventral hippocampus, but not the dorsal hippocampus, with the antagonist bicuculline, reverses the anxiolytic effect of running. Together, these results suggest that running improves anxiety regulation by engaging local inhibitory mechanisms in the ventral hippocampus.

Parsing the Role of the Hippocampus in Approach-Avoidance Conflict.

PubMed

Loh, Eleanor; Kurth-Nelson, Zeb; Berron, David; Dayan, Peter; Duzel, Emrah; Dolan, Ray; Guitart-Masip, Marc

2017-01-01

The hippocampus plays a central role in the approach-avoidance conflict that is central to the genesis of anxiety. However, its exact functional contribution has yet to be identified. We designed a novel gambling task that generated approach-avoidance conflict while controlling for spatial processing. We fit subjects' behavior using a model that quantified the subjective values of choice options, and recorded neural signals using functional magnetic resonance imaging (fMRI). Distinct functional signals were observed in anterior hippocampus, with inferior hippocampus selectively recruited when subjects rejected a gamble, to a degree that covaried with individual differences in anxiety. The superior anterior hippocampus, in contrast, uniquely demonstrated value signals that were potentiated in the context of approach-avoidance conflict. These results implicate the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety. Our findings highlight interactions between subregions of the hippocampus as an important focus for future study. © The Author 2016. Published by Oxford University Press.

Chewing Maintains Hippocampus-Dependent Cognitive Function

PubMed Central

Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2015-01-01

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research. PMID:26078711

Chewing Maintains Hippocampus-Dependent Cognitive Function.

PubMed

Chen, Huayue; Iinuma, Mitsuo; Onozuka, Minoru; Kubo, Kin-Ya

2015-01-01

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

Parsing the Role of the Hippocampus in Approach–Avoidance Conflict

PubMed Central

Loh, Eleanor; Kurth-Nelson, Zeb; Berron, David; Dayan, Peter; Duzel, Emrah; Dolan, Ray; Guitart-Masip, Marc

2017-01-01

Abstract The hippocampus plays a central role in the approach–avoidance conflict that is central to the genesis of anxiety. However, its exact functional contribution has yet to be identified. We designed a novel gambling task that generated approach–avoidance conflict while controlling for spatial processing. We fit subjects’ behavior using a model that quantified the subjective values of choice options, and recorded neural signals using functional magnetic resonance imaging (fMRI). Distinct functional signals were observed in anterior hippocampus, with inferior hippocampus selectively recruited when subjects rejected a gamble, to a degree that covaried with individual differences in anxiety. The superior anterior hippocampus, in contrast, uniquely demonstrated value signals that were potentiated in the context of approach–avoidance conflict. These results implicate the anterior hippocampus in behavioral avoidance and choice monitoring, in a manner relevant to understanding its role in anxiety. Our findings highlight interactions between subregions of the hippocampus as an important focus for future study. PMID:27993819

Hippocampus at 25

PubMed Central

Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

2017-01-01

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

Levothyroxine replacement therapy with vitamin E supplementation prevents the oxidative stress and apoptosis in hippocampus of hypothyroid rats.

PubMed

Guo, Yanyun; Wan, Si Yuan; Zhong, Xing; Zhong, Ming Kui; Pan, Tian Rong

2014-01-01

To examine the effect of levothyroxine (L-T4), vitamin E or both on oxidative stress status and hippocampal apoptosis in a propylthiouracil (PTU)-induced hypothyroid rat model. Sprague-Dawley rats were randomly divided into five groups: Control, PTU+PTU+L-T4+PTU+Vit E, PTU+Vit E+L-T4. In each group we assessed levels of serum triiodothyronine (T3), tetraiodothyronine (T4), thyroid stimulating hormone (TSH), hippocampus cellular apoptosis index (AI), hippocampus nicotinamide adenine denucleotide hydrogen (NADPH)oxidase and superoxide dismutase (SOD). 1) Compared with the control group, NADPH oxidase levels were significantly increased, and SOD levels were significantly reduced in the PTU groups (p<0.05). 2) Compared to the PTU group, SOD levels were significantly increased in the PTU+Vit E and PTU+L-T4+Vit E group (p<0.05). NADPH oxidase levels were significantly decreased in the PTU+L-T4, PTU+Vit E and PTU+ L-T4+Vit E group (p<0.05). 3) Compared with the control group, hippocampus AI increased significantly in the PTU group (p<0.05). Compared with the PTU group, hippocampus AI was significantly reduced in the PTU+L-T4 group and PTU+L-T4+Vit E group (p<0.05). 4) Hippocampus AI was positively correlated with NADPH oxidase expression levels in hippocampus tissue (r=0.644, p<0.01). Levothyroxine replacement therapy combined with vitamin E reduces hippocampus AI by improving oxidative stress. This study suggested that the mechanisms of hippocampus tissue injury in a hypothyroid rat model is related to hippocampus apoptosis from increased oxidative stress.

Breast Cancer Affects Both the Hippocampus Volume and the Episodic Autobiographical Memory Retrieval

PubMed Central

Bergouignan, Loretxu; Lefranc, Jean Pierre; Chupin, Marie; Morel, Nastassja; Spano, Jean Philippe; Fossati, Philippe

2011-01-01

Background Neuroimaging studies show the hippocampus is a crucial node in the neural network supporting episodic autobiographical memory retrieval. Stress-related psychiatric disorders, namely Major Depression and Post Traumatic Stress Disorder (PTSD), are related to reduced hippocampus volume. However, this is not the case for remitted breast cancer patients with co-morbid stress-related psychiatric disorders. This exception may be due to the fact that, consequently to the cancer experience as such, this population might already be characterized by a reduced hippocampus with an episodic autobiographical memory deficit. Methodology We scanned, with a 3T Siemens TRIO, 16 patients who had lived through a “standard experience of breast cancer” (breast cancer and a standard treatment in remission since 18 month) in the absence of any associated stress-related psychiatric or neurological disorder and 21 matched controls. We then assessed their episodic autobiographical memory retrieval ability. Principal Findings Remitted breast cancer patients had both a significantly smaller hippocampus and a significant deficit in episodic autobiographical memory retrieval. The hippocampus atrophy was characterized by a smaller posterior hippocampus. The posterior hippocampus volume was intimately related to the ability to retrieve negative memories and to the past experience of breast cancer or not. Conclusions/Significance These results provide two main findings: (1) we identify a new population with a specific reduction in posterior hippocampus volume that is independent of any psychiatric or neurological pathology; (2) we show the intimate relation of the posterior hippocampus to the ability to retrieve episodic autobiographical memories. These are significant findings as it is the first demonstration that indicates considerable long-term effects of living through the experience of breast cancer and shows very specific hippocampal atrophy with a functional deficit without any presence of psychiatric pathology. PMID:22016764

Hippocampus at 25.

PubMed

Eichenbaum, Howard; Amaral, David G; Buffalo, Elizabeth A; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G M; Moser, Edvard I; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

2016-10-01

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Diminished gray matter in the hippocampus of cannabis users: possible protective effects of cannabidiol.

PubMed

Demirakca, Traute; Sartorius, Alexander; Ende, Gabriele; Meyer, Nadja; Welzel, Helga; Skopp, Gisela; Mann, Karl; Hermann, Derik

2011-04-01

Chronic cannabis use has been associated with memory deficits and a volume reduction of the hippocampus, but none of the studies accounted for different effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). Using a voxel based morphometry approach optimized for small subcortical structures (DARTEL) gray matter (GM) concentration and volume of the hippocampus were measured in 11 chronic recreational cannabis users and 13 healthy controls, and correlated with THC and CBD from hair analyses. GM volume was calculated by modulating VBM using Jacobian determinants derived from the spatial normalization. Cannabis users showed lower GM volume located in a cluster of the right anterior hippocampus (P(uncorr)=0.002; effect size Cohen's d=1.34). In a regression analysis an inverse correlation of the ratio THC/CBD with the volume of the right hippocampus (P(uncorr) p<0.001, Cohen's d=3.43) was observed. Furthermore Cannabidiol correlated positively with GM concentration (unmodulated VBM data), but not with GM volume (modulated VBM) in the bilateral hippocampus (P=0.03 after correction for hippocampal volume; left hippocampus Cohen's d=4.37 and right hippocampus 4.65). Lower volume in the right hippocampus in chronic cannabis users was corroborated. Higher THC and lower CBD was associated with this volume reduction indicating neurotoxic effects of THC and neuroprotective effects of CBD. This confirms existing preclinical and clinical results. As a possible mechanism the influence of cannabinoids on hippocampal neurogenesis is suggested. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

PubMed

Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

2014-07-22

Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

History, anatomical nomenclature, comparative anatomy and functions of the hippocampal formation.

PubMed

El-Falougy, H; Benuska, J

2006-01-01

The complex structures in the cerebral hemispheres is included under one term, the limbic system. Our conception of this system and its special functions rises from the comparative neuroanatomical and neurophysiological studies. The components of the limbic system are the hippocampus, gyrus parahippocampalis, gyrus dentatus, gyrus cinguli, corpus amygdaloideum, nuclei anteriores thalami, hypothalamus and gyrus paraterminalis Because of its unique macroscopic and microscopic structure, the hippocampus is a conspicuous part of the limbic system. During phylogenetic development, the hippocampus developed from a simple cortical plate in amphibians into complex three-dimensional convoluted structure in mammals. In the last few decades, structures of the limbic system were extensively studied. Attention was directed to the physiological functions and pathological changes of the hippocampus. Experimental studies proved that the hippocampus has a very important role in the process of learning and memory. Another important functions of the hippocampus as a part of the limbic system is its role in regulation of sexual and emotional behaviour. The term "hippocampal formation" is defined as the complex of six structures: gyrus dentatus, hippocampus proprius, subiculum proprium, presubiculum, parasubiculum and area entorhinalis In this work we attempt to present a brief review of knowledge about the hippocampus from the point of view of history, anatomical nomenclature, comparative anatomy and functions (Tab. 1, Fig. 2, Ref. 33).

The Longevity of Hippocampus-Dependent Memory Is Orchestrated by the Locus Coeruleus-Noradrenergic System

PubMed Central

2017-01-01

The locus coeruleus is connected to the dorsal hippocampus via strong fiber projections. It becomes activated after arousal and novelty, whereupon noradrenaline is released in the hippocampus. Noradrenaline from the locus coeruleus is involved in modulating the encoding, consolidation, retrieval, and reversal of hippocampus-based memory. Memory storage can be modified by the activation of the locus coeruleus and subsequent facilitation of hippocampal long-term plasticity in the forms of long-term depression and long-term potentiation. Recent evidence indicates that noradrenaline and dopamine are coreleased in the hippocampus from locus coeruleus terminals, thus fostering neuromodulation of long-term synaptic plasticity and memory. Noradrenaline is an inductor of epigenetic modifications regulating transcriptional control of synaptic long-term plasticity to gate the endurance of memory storage. In conclusion, locus coeruleus activation primes the persistence of hippocampus-based long-term memory. PMID:28695015

Disrupted functional connectivity of the hippocampus in patients with hyperthyroidism: evidence from resting-state fMRI.

PubMed

Zhang, Wei; Liu, Xianjun; Zhang, Yi; Song, Lingheng; Hou, Jingming; Chen, Bing; He, Mei; Cai, Ping; Lii, Haitao

2014-10-01

The hippocampus expresses high levels of thyroid hormone receptors, suggesting that hippocampal functions, including cognition and regulation of mood, can be disrupted by thyroid pathology. Indeed, structural and functional alterations within the hippocampus have been observed in hyperthyroid patients. In addition to internal circuitry, hippocampal processing is dependent on extensive connections with other limbic and neocortical structures, but the effects of hyperthyroidism on functional connectivity (FC) with these areas have not been studied. The purpose of this study was to investigate possible abnormalities in the FC between the hippocampus and other neural structures in hyperthyroid patients using resting-state fMRI. Seed-based correlation analysis was performed on resting-state fMRI data to reveal possible differences in hippocampal FC between hyperthyroid patients and healthy controls. Correlation analysis was used to investigate the relationships between the strength of FC in regions showing significant group differences and clinical variables. Compared to controls, hyperthyroid patients showed weaker FC between the bilateral hippocampus and both the bilateral anterior cingulate cortex (ACC) and bilateral posterior cingulate cortex (PCC), as well as between the right hippocampus and right medial orbitofrontal cortex (mOFC). Disease duration was negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC and PCC. Levels of depression and anxiety were negatively correlated with FC strength between the bilateral hippocampus and bilateral ACC. Decreased functional connectivity between the hippocampus and bilateral ACC, PCC, and right mOFC may contribute to the emotional and cognitive dysfunction associated with hyperthyroidism. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Dissociation between dorsal and ventral hippocampal theta oscillations during decision-making.

PubMed

Schmidt, Brandy; Hinman, James R; Jacobson, Tara K; Szkudlarek, Emily; Argraves, Melissa; Escabí, Monty A; Markus, Etan J

2013-04-03

Hippocampal theta oscillations are postulated to support mnemonic processes in humans and rodents. Theta oscillations facilitate encoding and spatial navigation, but to date, it has been difficult to dissociate the effects of volitional movement from the cognitive demands of a task. Therefore, we examined whether volitional movement or cognitive demands exerted a greater modulating factor over theta oscillations during decision-making. Given the anatomical, electrophysiological, and functional dissociations along the dorsal-ventral axis, theta oscillations were simultaneously recorded in the dorsal and ventral hippocampus in rats trained to switch between place and motor-response strategies. Stark differences in theta characteristics were found between the dorsal and ventral hippocampus in frequency, power, and coherence. Theta power increased in the dorsal, but decreased in the ventral hippocampus, during the decision-making epoch. Interestingly, the relationship between running speed and theta power was uncoupled during the decision-making epoch, a phenomenon limited to the dorsal hippocampus. Theta frequency increased in both the dorsal and ventral hippocampus during the decision epoch, although this effect was greater in the dorsal hippocampus. Despite these differences, ventral hippocampal theta was responsive to the navigation task; theta frequency, power, and coherence were all affected by cognitive demands. Theta coherence increased within the dorsal hippocampus during the decision-making epoch on all three tasks. However, coherence selectively increased throughout the hippocampus (dorsal to ventral) on the task with new hippocampal learning. Interestingly, most results were consistent across tasks, regardless of hippocampal-dependent learning. These data indicate increased integration and cooperation throughout the hippocampus during information processing.

Hippocampus and Amygdala Morphology in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Plessen, Kerstin J.; Bansal, Ravi; Zhu, Hongtu; Whiteman, Ronald; Amat, Jose; Quackenbush, Georgette A.; Martin, Laura; Durkin, Kathleen; Blair, Clancy; Royal, Jason; Hugdahl, Kenneth; Peterson, Bradley S.

2008-01-01

Context Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. Objective To study the morphology of the hippocampus and amygdala in children with ADHD. Design A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. Settings University research institute. Patients One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63 healthy controls. Main Outcome Measures Volumes and measures of surface morphology for the hippocampus and amygdala. Results The hippocampus was larger bilaterally in the ADHD group than in the control group (t=3.35; P<.002). Detailed surface analyses of the hippocampus further localized these differences to an enlarged head of the hippocampus in the ADHD group. Although conventional measures did not detect significant differences in amygdalar volumes, surface analyses indicated the presence of reduced size bilaterally over the area of the basolateral complex. Correlations with prefrontal measures suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. Conclusions The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence of disturbances in the perception of time, temporal processing (eg, delay aversion), and stimulus seeking associated with ADHD. Disrupted connections between the amygdala and orbitofrontal cortex may contribute to behavioral disinhibition. Our findings suggest involvement of the limbic system in the pathophysiology of ADHD. PMID:16818869

Knowing what from where: Hippocampal connectivity with temporoparietal cortex at rest is linked to individual differences in semantic and topographic memory.

PubMed

Sormaz, Mladen; Jefferies, Elizabeth; Bernhardt, Boris C; Karapanagiotidis, Theodoros; Mollo, Giovanna; Bernasconi, Neda; Bernasconi, Andrea; Hartley, Tom; Smallwood, Jonathan

2017-05-15

The hippocampus contributes to episodic, spatial and semantic aspects of memory, yet individual differences within and between these functions are not well-understood. In 136 healthy individuals, we investigated whether these differences reflect variation in the strength of connections between functionally-specialised segments of the hippocampus and diverse cortical regions that participate in different aspects of memory. Better topographical memory was associated with stronger connectivity between lingual gyrus and left anterior, rather than posterior, hippocampus. Better semantic memory was associated with increased connectivity between the intracalcarine/cuneus and left, rather than right, posterior hippocampus. Notably, we observed a double dissociation between semantic and topographical memory: better semantic memory was associated with stronger connectivity between left temporoparietal cortex and left anterior hippocampus, while better topographic memory was linked to stronger connectivity with right anterior hippocampus. Together these data support a division-of-labour account of hippocampal functioning: at the population level, differences in connectivity across the hippocampus reflect functional specialisation for different facets of memory, while variation in these connectivity patterns across individuals is associated with differences in the capacity to retrieve different types of information. In particular, within-hemisphere connectivity between hippocampus and left temporoparietal cortex supports conceptual processing at the expense of spatial ability. Copyright © 2017. Published by Elsevier Inc.

Dysfunction of Iron Metabolism and Iron-Regulatory Proteins in the Rat Hippocampus After Heat Stroke.

PubMed

Liu, Jing; Wan, Shengming; Zhang, Yun; Zhang, Shu; Zhang, Hongying; Wu, Shiwen

2018-05-11

Heat stroke, the most serious type of heat illness, refers to the presence of hyperthermia (core temperature >40°C), accompanied by central nervous system dysfunction. The hippocampus is a particularly vulnerable region in the early stage of heat stroke. Increasing evidence suggests that dysregulation of brain iron metabolism is involved in many neurodegenerative diseases. However, whether heat stroke causes dysfunction of iron metabolism, as well as iron-regulatory proteins, in the hippocampus remains unknown. The present study was conducted to explore the effects on spatial learning and memory, as well as iron content, ferroportin 1 (Fpn1), and hepcidin expression in the hippocampus after heat stroke in rats. Compared with the Sham group, learning ability and memory declined in rats after heat stroke. Iron concentration was significantly increased in the hippocampus. Expression of Fpn1 protein significantly decreased in the hippocampus, while expression of hepcidin increased. Interestingly, Fpn1 mRNA expression in the hippocampus increased. Our data thereby indicate that heat stroke can decrease learning ability and memory in rats. The mechanism may be related to changes of iron levels, as well as Fpn1 and hepcidin expression, in the hippocampus. Furthermore, hepcidin may rapidly decrease cellular Fpn1 protein levels, even under conditions of iron loading, indicating that hepcidin is a more dominant regulator of Fpn1 than is iron.

Toxicological study of injuries of rat’s hippocampus after lead poisoning by synchrotron microradiography and elemental mapping

NASA Astrophysics Data System (ADS)

Liang, Feng; Zhang, Guilin; Xiao, Xianghui; Cai, Zhonghou; Lai, Barry; Hwu, Yeukuang; Yan, Chonghuai; Xu, Jian; Li, Yulan; Tan, Mingguang; Zhang, Chuanfu; Li, Yan

2010-09-01

The hippocampus, a major component of the brain, is one of the target nervous organs in lead poisoning. In this work, a rat's hippocampal injury caused by lead was studied. The lead concentrations in blood, bone and hippocampus collected from rats subject to lead poisoning were quantified by Inductively Coupled Plasma Mass Spectrometry while morphological information and elemental distributions in the hippocampus were obtained with synchrotron radiation X-ray phase contrast imaging and synchrotron radiation micro-beam X-ray fluorescence, respectively. For comparison, identical characterization of the specimens from the rats in the control group was done in parallel. Results show that the ratios between the lead content in the treated group and that in the control group of the hippocampus, bone, and blood are about 2.66, 236, and 39.6, respectively. Analysis also revealed that some health elements such as S, K, Cl and P increase in the regions with high lead content in the treated hippocampus. Morphological differences between the normal and lead-exposed hippocampus specimens in some local areas were observed. Explicitly, the structure of the lead-exposed hippocampus was tortuous and irregular, and the density of the neurons in the Dentate Gyrus was significantly lower than that from the control group. The study shows that the synchrotron radiation methods are very powerful for investigating structural injury caused by heavy metals in the nervous system.

A Critical Role for the Hippocampus in the Valuation of Imagined Outcomes

PubMed Central

Lebreton, Maël; Bertoux, Maxime; Boutet, Claire; Lehericy, Stéphane; Dubois, Bruno; Fossati, Philippe; Pessiglione, Mathias

2013-01-01

Many choice situations require imagining potential outcomes, a capacity that was shown to involve memory brain regions such as the hippocampus. We reasoned that the quality of hippocampus-mediated simulation might therefore condition the subjective value assigned to imagined outcomes. We developed a novel paradigm to assess the impact of hippocampus structure and function on the propensity to favor imagined outcomes in the context of intertemporal choices. The ecological condition opposed immediate options presented as pictures (hence directly observable) to delayed options presented as texts (hence requiring mental stimulation). To avoid confounding simulation process with delay discounting, we compared this ecological condition to control conditions using the same temporal labels while keeping constant the presentation mode. Behavioral data showed that participants who imagined future options with greater details rated them as more likeable. Functional MRI data confirmed that hippocampus activity could account for subjects assigning higher values to simulated options. Structural MRI data suggested that grey matter density was a significant predictor of hippocampus activation, and therefore of the propensity to favor simulated options. Conversely, patients with hippocampus atrophy due to Alzheimer's disease, but not patients with Fronto-Temporal Dementia, were less inclined to favor options that required mental simulation. We conclude that hippocampus-mediated simulation plays a critical role in providing the motivation to pursue goals that are not present to our senses. PMID:24167442

Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

PubMed

Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

2015-02-01

Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical exercise may serve as a means to delay the onset of AD. Copyright © 2014 Elsevier Inc. All rights reserved.

Environmental enrichment reverses histone methylation changes in the aged hippocampus and restores age-related memory deficits.

PubMed

Morse, Sarah J; Butler, Anderson A; Davis, Robin L; Soller, Ian J; Lubin, Farah D

2015-04-01

A decline in long-term memory (LTM) formation is a common feature of the normal aging process, which corresponds with abnormal expression of memory-related genes in the aged hippocampus. Epigenetic modulation of chromatin structure is required for proper transcriptional control of genes, such as the brain-derived neurotrophic factor (Bdnf) and Zif268 in the hippocampus during the consolidation of new memories. Recently, the view has emerged that aberrant transcriptional regulation of memory-related genes may be reflective of an altered epigenetic landscape within the aged hippocampus, resulting in memory deficits with aging. Here, we found that baseline resting levels for tri-methylation of histone H3 at lysine 4 (H3K4me3) and acetylation of histone H3 at lysine 9 and 14 (H3K9,K14ac) were altered in the aged hippocampus as compared to levels in the hippocampus of young adult rats. Interestingly, object learning failed to increase activity-dependent H3K4me3 and di-methylation of histone H3 at lysine 9 (H3K9me2) levels in the hippocampus of aged adults as compared to young adults. Treatment with the LSD-1 histone demethylase inhibitor, t-PCP, increased baseline resting H3K4me3 and H3K9,K14ac levels in the young adult hippocampus, while young adult rats exhibited similar memory deficits as observed in aged rats. After environmental enrichment (EE), we found that object learning induced increases in H3K4me3 levels around the Bdnf, but not the Zif268, gene region in the aged hippocampus and rescued memory deficits in aged adults. Collectively, these results suggest that histone lysine methylation levels are abnormally regulated in the aged hippocampus and identify histone lysine methylation as a transcriptional mechanism by which EE may serve to restore memory formation with aging.

[Effect of tongluo xingnao effervescent tablet on learning and memory of AD rats and expression of insulin-degrading enzyme in hippocampus].

PubMed

Zhang, Yin-Jie; Dai, Yuan; Hu, Yong; Ma, Yun-Tong; Xu, Shi-Jun; Wang, Yong-Yan

2013-09-01

To study the effect of Tongluo Xingnao effervescent tablet on learning and memory of dementia rats induced by injection of Abeta25-35 in hippocampus and expression of insulin-degrading enzyme in hippocampus, in order to provide basis for preventing and treating senile dementia. The dementia rat model was established by injecting Abeta25-35 in hippocampus. The rats were divided into the model control group, the Aricept (1.4 mg x kg(-1)) group, and Tongluo Xingnao effervescent tablet high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups. A sham operation group was established by injecting normal saline in hippocampus. The rats were orally given drugs for 90 days, once a day. Their learning and memory were tested by using Morris water maze. Immunohistochemistry and image analysis were utilized for a quantitative analysis on the expression of insulin-degrading enzyme in hippocampus. Tongluo Xingnao effervescent tablet could significantly shorten the escape latency of rats in the directional navigation test, prolong the retention time in the first quadrant dwell, decrease the retention time in the third quadrant dwell, increase the frequency of crossing the platform, show a more notable statistical significance than the model control group (P < 0.05). Additionally, it could also remarkably increase the average optical density of insulin-degrading enzyme in hippocampus, promote the expression of insulin-degrading enzyme in hippocampus, and show a more notable statistical significance than the model control group (P < 0.05). Tongluo Xingnao effervescent tablet has the effects of improving learning and memory capacity of AD rats and promoting the expression of insulin-degrading enzyme in hippocampus. Its effect in promoting intelligence will be related to increased insulin-degrading enzyme in hippocampus.

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

PubMed Central

Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R; Flor, Herta

2009-01-01

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning. PMID:19200075

Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs.

PubMed

Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A; Goosens, Ki Ann; Bendor, Daniel

2016-01-01

The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1-2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.

Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs

PubMed Central

Varela, Carmen; Weiss, Sarah; Meyer, Retsina; Halassa, Michael; Biedenkapp, Joseph; Wilson, Matthew A.; Goosens, Ki Ann

2016-01-01

The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1–2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation. PMID:27145133

Sleep-dependent directional coupling between human neocortex and hippocampus.

PubMed

Wagner, Tobias; Axmacher, Nikolai; Lehnertz, Klaus; Elger, Christian E; Fell, Jürgen

2010-02-01

Complex interactions between neocortex and hippocampus are the neural basis of memory formation. Two-step theories of memory formation suggest that initial encoding of novel information depends on the induction of rapid plasticity within the hippocampus, and is followed by a second sleep-dependent step of memory consolidation. These theories predict information flow from the neocortex into the hippocampus during waking state and in the reverse direction during sleep. However, experimental evidence that interactions between hippocampus and neocortex have a predominant direction which reverses during sleep rely on cross-correlation analysis of data from animal experiments and yielded inconsistent results. Here, we investigated directional coupling in intracranial EEG data from human subjects using a phase-modeling approach which is well suited to reveal functional interdependencies in oscillatory data. In general, we observed that the anterior hippocampus predominantly drives nearby and remote brain regions. Surprisingly, however, the influence of neocortical regions on the hippocampus significantly increased during sleep as compared to waking state. These results question the standard model of hippocampal-neocortical interactions and suggest that sleep-dependent consolidation is accomplished by an active retrieval of hippocampal information by the neocortex. Copyright 2009 Elsevier Srl. All rights reserved.

HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

PubMed Central

Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

2011-01-01

Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

Standardised extract of Bacopa monniera (CDRI-08) improves contextual fear memory by differentially regulating the activity of histone acetylation and protein phosphatases (PP1α, PP2A) in hippocampus.

PubMed

Preethi, Jayakumar; Singh, Hemant K; Venkataraman, Jois Shreyas; Rajan, Koilmani Emmanuvel

2014-05-01

Contextual fear conditioning is a paradigm for investigating cellular mechanisms involved in hippocampus-dependent memory. Earlier, we showed that standardised extract of Bacopa monniera (CDRI-08) improves hippocampus-dependent learning in postnatal rats by elevating the level of serotonin (5-hydroxytryptamine, 5-HT), activate 5-HT3A receptors, and cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein. In this study, we have further examined the molecular mechanism of CDRI-08 in hippocampus-dependent memory and compared to the histone deacetylase (HDACs) inhibitor sodium butyrate (NaB). To assess the hippocampus-dependent memory, wistar rat pups were subjected to contextual fear conditioning (CFC) following daily (postnatal days 15-29) administration of vehicle solution (0.5 % gum acacia + 0.9 % saline)/CDRI-08 (80 mg/kg, p.o.)/NaB (1.2 g/kg in PBS, i.p.). CDRI-08/NaB treated group showed enhanced freezing behavior compared to control group when re-exposed to the same context. Administration of CDRI-08/NaB resulted in activation of extracellular signal-regulated kinase ERK/CREB signaling cascade and up-regulation of p300, Ac-H3 and Ac-H4 levels, and down-regulation of HDACs (1, 2) and protein phosphatases (PP1α, PP2A) in hippocampus following CFC. This would subsequently result in an increased brain-derived neurotrophic factor (Bdnf) (exon IV) mRNA in hippocampus. Altogether, our results indicate that CDRI-08 enhances hippocampus-dependent contextual memory by differentially regulating histone acetylation and protein phosphatases in hippocampus.

Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

PubMed Central

2013-01-01

Background Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms. PMID:24176048

Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

PubMed

Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

2015-05-30

Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Julius Caesar Arantius (Giulio Cesare Aranzi, 1530-1589) and the hippocampus of the human brain: history behind the discovery.

PubMed

Bir, Shyamal C; Ambekar, Sudheer; Kukreja, Sunil; Nanda, Anil

2015-04-01

Julius Caesar Arantius is one of the pioneer anatomists and surgeons of the 16th century who discovered the different anatomical structures of the human body. One of his prominent discoveries is the hippocampus. At that time, Arantius originated the term hippocampus, from the Greek word for seahorse (hippos ["horse"] and kampos ["sea monster"]). Arantius published his description of the hippocampus in 1587, in the first chapter of his work titled De Humano Foetu Liber. Numerous nomenclatures of this structure, including "white silkworm," "Ammon's horn," and "ram's horn" were proposed by different scholars at that time. However, the term hippocampus has become the most widely used in the literature.

Can the hippocampus tell time? The temporo-septal engram shift model.

PubMed

Lytton, W W; Lipton, P

1999-08-02

An essential feature of episodic memory, the type of memory dependent on hippocampus, is that individual memories belong to particular moments in time. Recent PET studies suggest that memory encoding and recall occur at different locations in human hippocampus. Coupled with other attributes of hippocampus, this suggested to us that the septo-temporal hippocampal axis may play an important role in time perception. We propose a temporo-septal engram shift model of hippocampal memory. The model posits that memories gradually move along the hippocampus from a temporal encoding site to ever more septal sites from which they are recalled. We propose that the sense of time is encoded by the location of the engram along the temporo-septal axis.

Hippocampal and posterior parietal contributions to developmental increases in visual short-term memory capacity.

PubMed

von Allmen, David Yoh; Wurmitzer, Karoline; Klaver, Peter

2014-10-01

Developmental increases in visual short-term memory (VSTM) capacity have been associated with changes in attention processing limitations and changes in neural activity within neural networks including the posterior parietal cortex (PPC). A growing body of evidence suggests that the hippocampus plays a role in VSTM, but it is unknown whether the hippocampus contributes to the capacity increase across development. We investigated the functional development of the hippocampus and PPC in 57 children, adolescents and adults (age 8-27 years) who performed a visuo-spatial change detection task. A negative relationship between age and VSTM related activity was found in the right posterior hippocampus that was paralleled by a positive age-activity relationship in the right PPC. In the posterior hippocampus, VSTM related activity predicted individual capacity in children, whereas neural activity in the right anterior hippocampus predicted individual capacity in adults. The findings provide first evidence that VSTM development is supported by an integrated neural network that involves hippocampal and posterior parietal regions.

Initialisation of 3D level set for hippocampus segmentation from volumetric brain MR images

NASA Astrophysics Data System (ADS)

Hajiesmaeili, Maryam; Dehmeshki, Jamshid; Bagheri Nakhjavanlo, Bashir; Ellis, Tim

2014-04-01

Shrinkage of the hippocampus is a primary biomarker for Alzheimer's disease and can be measured through accurate segmentation of brain MR images. The paper will describe the problem of initialisation of a 3D level set algorithm for hippocampus segmentation that must cope with the some challenging characteristics, such as small size, wide range of intensities, narrow width, and shape variation. In addition, MR images require bias correction, to account for additional inhomogeneity associated with the scanner technology. Due to these inhomogeneities, using a single initialisation seed region inside the hippocampus is prone to failure. Alternative initialisation strategies are explored, such as using multiple initialisations in different sections (such as the head, body and tail) of the hippocampus. The Dice metric is used to validate our segmentation results with respect to ground truth for a dataset of 25 MR images. Experimental results indicate significant improvement in segmentation performance using the multiple initialisations techniques, yielding more accurate segmentation results for the hippocampus.

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

PubMed

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

EPA Science Inventory

Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

Untangling elevation-related differences in the hippocampus in food-caching mountain chickadees: the effect of a uniform captive environment.

PubMed

Freas, C A; Bingman, K; Ladage, L D; Pravosudov, V V

2013-01-01

Variation in environmental conditions associated with differential selection on spatial memory has been hypothesized to result in evolutionary changes in the morphology of the hippocampus, a brain region involved in spatial memory. At the same time, it is well known that the morphology of the hippocampus might also be directly affected by environmental conditions. Understanding the role of environment-based plasticity is therefore critical when investigating potential adaptive evolutionary changes in the hippocampus associated with environmental variation. We previously demonstrated large elevation-related variation in hippocampus morphology in mountain chickadees over an extremely small spatial scale. We hypothesized that this variation is related to differential selection pressures associated with differences in winter climate severity along an elevation gradient, which make different demands on spatial memory used for food cache retrieval. Here, we tested whether such variation is experience based, generated by potential differences in the environment, by comparing the hippocampus morphology of chickadees from different elevations maintained in a uniform captive environment in a laboratory with those sampled directly from the wild. In addition, we compared hippocampal neuron soma size in chickadees sampled directly from the wild with those maintained in laboratory conditions with restricted and unrestricted spatial memory use via manipulation of food-caching experiences to test whether memory use can affect neuron soma size. There were significant elevation-related differences in hippocampus volume and the total number of hippocampal neurons, but not in neuron soma size, in captive birds. Captive environmental conditions were associated with a large reduction in hippocampus volume and neuron soma size, but not in the total number of neurons or in neuron soma size in other telencephalic regions. Restriction of memory use while in laboratory conditions produced no significant effects on hippocampal neuron soma size. Overall our results showed that captivity has a strong effect on hippocampus volume, which could be due, at least partly, to a reduction in neuron soma size specifically in the hippocampus, but it did not override elevation-related differences in hippocampus volume or in the total number of hippocampal neurons. These data are consistent with the idea of the adaptive nature of the elevation-related differences associated with selection on spatial memory, while at the same time demonstrating additional environment-based plasticity in hippocampus volume, but not in neuron numbers. Our results, however, cannot rule out that the differences between elevations might still be driven by some developmental or early posthatching conditions/experiences. © 2013 S. Karger AG, Basel.

Post-Training Reversible Inactivation of the Hippocampus Enhances Novel Object Recognition Memory

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Hawk, Joshua D.; Abel, Ted; Havekes, Robbert

2010-01-01

Research on the role of the hippocampus in object recognition memory has produced conflicting results. Previous studies have used permanent hippocampal lesions to assess the requirement for the hippocampus in the object recognition task. However, permanent hippocampal lesions may impact performance through effects on processes besides memory…

Pattern Separation Deficits Following Damage to the Hippocampus

ERIC Educational Resources Information Center

Kirwan, C. Brock; Hartshorn, Andrew; Stark, Shauna M.; Goodrich-Hunsaker, Naomi J.; Hopkins, Ramona O.; Stark, Craig E. L.

2012-01-01

Computational models of hippocampal function propose that the hippocampus is capable of rapidly storing distinct representations through a process known as pattern separation. This prediction is supported by electrophysiological data from rodents and neuroimaging data from humans. Here, we test the prediction that damage to the hippocampus would…

Experience-Dependent Epigenomic Reorganization in the Hippocampus

ERIC Educational Resources Information Center

Duke, Corey G.; Kennedy, Andrew J.; Gavin, Cristin F.; Day, Jeremy J.; Sweatt, J. David

2017-01-01

Using a hippocampus-dependent contextual threat learning and memory task, we report widespread, coordinated DNA methylation changes in CA1 hippocampus of Sprague-Dawley rats specific to threat learning at genes involved in synaptic transmission. Experience-dependent alternations in gene expression and DNA methylation were observed as early as 1 h…

Septohippocampal Acetylcholine: Involved in but Not Necessary for Learning and Memory?

ERIC Educational Resources Information Center

Parent, Marise B.; Baxter, Mark G.

2004-01-01

The neurotransmitter acetylcholine (ACh) has been accorded an important role in supporting learning and memory processes in the hippocampus. Cholinergic activity in the hippocampus is correlated with memory, and restoration of ACh in the hippocampus after disruption of the septohippocampal pathway is sufficient to rescue memory. However, selective…

Idiothetic input into object-place configuration as the contribution to memory of the monkey and human hippocampus: a review.

PubMed

Gaffan, D

1998-11-01

Memory for object-place configurations appears to be a common function of the hippocampus in the human and monkey brain. The nature of the spatial information which enters into these object-configural memories in the primate, and the location of the memories themselves, have remained obscure, however. In the rat, much evidence indicates that the hippocampus processes idiothetic spatial information, an estimate of the animal's current environmental location derived from path integration. I propose that in primates the hippocampus provides idiothetic information about the environmental location of body parts, and that the main function of this information in the primate brain is to become configured with object-identity information provided by temporal lobe cortex outside the hippocampus.

Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats.

PubMed

Ma, Jingyi; Leung, L Stan

2018-02-15

The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABA A receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

Normative volumetric data of the developing hippocampus in children based on magnetic resonance imaging.

PubMed

Pfluger, T; Weil, S; Weis, S; Vollmar, C; Heiss, D; Egger, J; Scheck, R; Hahn, K

1999-04-01

To acquire normative data of the hippocampus and its postnatal growth in 50 children (age, 1 month to 15 years) without epilepsy. Morphometry of the hippocampus was carried out by using a spoiled FLASH 3D sequence (sagittal orientation), whereas the volume of the brain was assessed with a T2-weighted spin-echo sequence (transverse orientation). The volume of the hippocampus and the brain was determined by following Cavalieri's principle. Growth curves of the brain and hippocampus were fitted to a nonlinear Boltzmann sigmoidal equation. Intra-/interobserver coefficient of variation was 2.0/4.9% for hippocampal volume measurements and 2.0/2.1% for brain volumetry. A significant difference in volume was noted between the right and left hippocampus (p < 0.001), with the right side being larger on average by 0.10 cc. Correlation coefficients of growth curves ranged between 0.71 and 0.94. Growth curves demonstrated a faster development of the hippocampus in girls. A steeper slope of hippocampal growth as compared with brain growth was found in girls, whereas in boys, the slope of brain growth was steeper. Our findings will be of help in evaluating vulnerable phases of the hippocampal formation with accelerated growth, thereby leading to a better understanding of the development of hippocampal sclerosis in early childhood.

Upregulation of MAOA in the hippocampus results in delayed depressive-like behaviors in burn mice.

PubMed

Wang, Zhen; Chen, Lu; Rong, Xinzhou; Wang, Xuemin

2017-04-14

To observe depressive-like behavior and hippocampus monoamine oxidase A (MAOA) changes in burned mice. We tested depression and anxiety like behaviors of burn C57 mice with the sucrose preference test, forced swimming test (FST), open field test and elevated plus maze test and then detected the MAOA content and MAOA gene transcriptional levels in the hippocampus with western blot analysis and real-time quantitative PCR analysis. We then sought to reverse depressive-like behavior of burned mice with an MAOA inhibitor. (1) Mice showed depressive and anxiety like behaviors one week after they were burned; (2) The content of MAOA in the hippocampus of burned mice was significantly higher than that in control mice (P<0.05); (3) MAOA gene transcription in the hippocampus of burned mice was significantly increased (MAOA mRNA was increased, P<0.05); (4) treatment with a MAOA inhibitor (phenelzine) significantly increased the sucrose preference rate and decreased FST immobility time in burned mice, and also decreased elevated expression of MAOA in the hippocampus of burned mice. Burned mice showed "delayed" depressive-like behavior combined with a degree of anxiety; this phenomenon is likely associated with the increase in MAOA expression in the hippocampus. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

Investigation of Propolis’ Effect on Thiobarbituric Acid Reactive Substances and Anti-Oxidant Enzyme Levels of Hippocampus in Diabetic Rats Induced by Streptozotocin

PubMed Central

Köksal, Burcu; Emre, Memet Hanifi; Polat, Alaadin

2015-01-01

BACKGROUND: Propolis is an organic resinous viscous substance collected from flower bud and plant sprig by bees. Propolis has a potential treatment agent for oxidative damage caused by diabetes in hippocampus due to its flavonoid and phenolic content. AIM: In this study effect of propolis on thiobarbituric acid reactive substances and anti-oxidative enzyme levels of hippocampus in diabetic rats induced by streptozotocin was investigated. MATERIALS AND METHODS: The study involved measuring levels of SOD, CAT, GSH-Px and TBARs in hippocampus tissue of STZ-induced diabetic rats (Adult Male Sprague Dawley rats) after applying propolis for one month. The subjects of the study were composed of 51 rats randomly assigned to four groups (Control, STZ, P+STZ and STZ+P). For analysis of data, Kruskal Wallis Test was utilized. RESULTS: The findings of the study showed that there were no significant difference in the levels of TBARS, SOD, CAT and GSH-Px of hippocampus across the groups. CONCLUSION: Propolis application in four-week duration does not have effect on TBARS, SOD, CAT and GSH-Px levels of hippocampus of diabetic rats. These findings mean that more time for observing oxidative harms on hippocampus is needed. PMID:27275196

Mechanisms for widespread hippocampal involvement in cognition

PubMed Central

Shohamy, Daphna; Turk-Browne, Nicholas B.

2014-01-01

The quintessential memory system in the human brain — the hippocampus and surrounding medial temporal lobe (MTL) — is often treated as a module for the formation of conscious, or declarative memories. However, growing evidence suggests that the hippocampus plays a broader role in memory and cognition and that theories organizing memory into strictly dedicated systems may need to be updated. We first consider the historical evidence for the specialized role of the hippocampus in declarative memory. Then, we describe the serendipitous encounter that motivated this special section, based on parallel research from our labs that suggested a more pervasive contribution of the hippocampus to cognition beyond declarative memory. Finally, we develop a theoretical framework that describes two general mechanisms for how the hippocampus interacts with other brain systems and cognitive processes: the Memory Modulation Hypothesis, in which mnemonic representations in the hippocampus modulate the operation of other systems, and the Adaptive Function Hypothesis, in which specialized computations in the hippocampus are recruited as a component of both mnemonic and non-mnemonic functions. This framework is consistent with an emerging view that the most fertile ground for discovery in cognitive psychology and neuroscience lies at the interface between parts of the mind and brain that have traditionally been studied in isolation. PMID:24246058

Methionine increases BDNF DNA methylation and improves memory in epilepsy.

PubMed

Parrish, R Ryley; Buckingham, Susan C; Mascia, Katherine L; Johnson, Jarvis J; Matyjasik, Michal M; Lockhart, Roxanne M; Lubin, Farah D

2015-04-01

Temporal lobe epilepsy (TLE) patients exhibit signs of memory impairments even when seizures are pharmacologically controlled. Surprisingly, the underlying molecular mechanisms involved in TLE-associated memory impairments remain elusive. Memory consolidation requires epigenetic transcriptional regulation of genes in the hippocampus; therefore, we aimed to determine how epigenetic DNA methylation mechanisms affect learning-induced transcription of memory-permissive genes in the epileptic hippocampus. Using the kainate rodent model of TLE and focusing on the brain-derived neurotrophic factor (Bdnf) gene as a candidate of DNA methylation-mediated transcription, we analyzed DNA methylation levels in epileptic rats following learning. After detection of aberrant DNA methylation at the Bdnf gene, we investigated functional effects of altered DNA methylation on hippocampus-dependent memory formation in our TLE rodent model. We found that behaviorally driven BdnfDNA methylation was associated with hippocampus-dependent memory deficits. Bisulfite sequencing revealed that decreased BdnfDNA methylation levels strongly correlated with abnormally high levels of BdnfmRNA in the epileptic hippocampus during memory consolidation. Methyl supplementation via methionine (Met) increased BdnfDNA methylation and reduced BdnfmRNA levels in the epileptic hippocampus during memory consolidation. Met administration reduced interictal spike activity, increased theta rhythm power, and reversed memory deficits in epileptic animals. The rescue effect of Met treatment on learning-induced BdnfDNA methylation, Bdnf gene expression, and hippocampus-dependent memory, were attenuated by DNA methyltransferase blockade. Our findings suggest that manipulation of DNA methylation in the epileptic hippocampus should be considered as a viable treatment option to ameliorate memory impairments associated with TLE.

Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval.

PubMed

Yassa, Michael A; Reagh, Zachariah M

2013-01-01

Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being "recontextualization," or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate.

Competitive Trace Theory: A Role for the Hippocampus in Contextual Interference during Retrieval

PubMed Central

Yassa, Michael A.; Reagh, Zachariah M.

2013-01-01

Much controversy exists regarding the role of the hippocampus in retrieval. The two dominant and competing accounts have been the Standard Model of Systems Consolidation (SMSC) and Multiple Trace Theory (MTT), which specifically make opposing predictions as to the necessity of the hippocampus for retrieval of remote memories. Under SMSC, memories eventually become independent of the hippocampus as they become more reliant on cortical connectivity, and thus the hippocampus is not required for retrieval of remote memories, only recent ones. MTT on the other hand claims that the hippocampus is always required no matter the age of the memory. We argue that this dissociation may be too simplistic, and a continuum model may be better suited to address the role of the hippocampus in retrieval of remote memories. Such a model is presented here with the main function of the hippocampus during retrieval being “recontextualization,” or the reconstruction of memory using overlapping traces. As memories get older, they are decontextualized due to competition among partially overlapping traces and become more semantic and reliant on neocortical storage. In this framework dubbed the Competitive Trace Theory (CTT), consolidation events that lead to the strengthening of memories enhance conceptual knowledge (semantic memory) at the expense of contextual details (episodic memory). As a result, remote memories are more likely to have a stronger semantic representation. At the same time, remote memories are also more likely to include illusory details. The CTT is a novel candidate model that may provide some resolution to the memory consolidation debate. PMID:23964216

Structural Hippocampal Anomalies in a Schizophrenia Population Correlate with Navigation Performance on a Wayfinding Task

PubMed Central

Ledoux, Andrée-Anne; Boyer, Patrice; Phillips, Jennifer L.; Labelle, Alain; Smith, Andra; Bohbot, Véronique D.

2014-01-01

Episodic memory, related to the hippocampus, has been found to be impaired in schizophrenia. Further, hippocampal anomalies have also been observed in schizophrenia. This study investigated whether average hippocampal gray matter (GM) would differentiate performance on a hippocampus-dependent memory task in patients with schizophrenia and healthy controls. Twenty-one patients with schizophrenia and 22 control participants were scanned with an MRI while being tested on a wayfinding task in a virtual town (e.g., find the grocery store from the school). Regressions were performed for both groups individually and together using GM and performance on the wayfinding task. Results indicate that controls successfully completed the task more often than patients, took less time, and made fewer errors. Additionally, controls had significantly more hippocampal GM than patients. Poor performance was associated with a GM decrease in the right hippocampus for both groups. Within group regressions found an association between right hippocampi GM and performance in controls and an association between the left hippocampi GM and performance in patients. A second analysis revealed that different anatomical GM regions, known to be associated with the hippocampus, such as the parahippocampal cortex, amygdala, medial, and orbital prefrontal cortices, covaried with the hippocampus in the control group. Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus in the patient group but the orbital frontal cortex did not, supporting the hypothesis of impaired connectivity between the hippocampus and the frontal cortex in schizophrenia. These results present important implications for creating intervention programs aimed at measuring functional and structural changes in the hippocampus in schizophrenia. PMID:24672451

Species and Size Composition of Seahorses (Genus Hippocampus, Family Syngnathidae) in the Coastal Waters and Local Market of Kota Kinabalu, Sabah, Malaysia

PubMed Central

Shapawi, Rossita; Anyie, Adrian Leslie; Hussien, Muhammad Ali Syed; Zuldin, Wahidatul Husna

2015-01-01

Seahorse diversity (genus Hippocampus, Family Syngnathidae), species identification, size composition and sexual dimorphism were studied from November 2012 to March 2013 in selected coastal waters around Kota Kinabalu, Sabah and the local market trade. Six species of seahorses were identified in the study: (1) Hippocampus barbouri, (2) Hippocampus comes, (3) Hippocampus kelloggi, (4) Hippocampus kuda, (5) Hippocampus spinosissimus and (6) Hippocampus trimaculatus. All six species were sold at the local market, and the dried seahorses were obtained mainly by local fishermen using trawl by-catch method and traded as traditional medicine, souvenirs and other uses. Four species were identified by direct samplings in various different habitats of Kota Kinabalu coastal waters: (1) H. barbouri, (2) H. comes, (3) H. kuda, and (4) H. spinosissimus. Based on the results, H. comes was the largest in size among the four fresh/live species found (mean standard length [SL]: 148.25±1.26 mm), whereas H. barbouri was the smallest species (mean SL: 129±7.81 mm). For the dried samples, H. kelloggi was the largest (mean SL: 245.25±14.55 mm) and H. barbouri was the smallest (mean SL: 127.21±10.01 mm). No significant difference (p>0.05) was observed between the lengths of males and females in every seahorse species, and there was no sexual size dimorphism in any of the species. The findings from the study are significant to provide baseline data for the conservation efforts of these unique marine teleost. PMID:26868706

Species and Size Composition of Seahorses (Genus Hippocampus, Family Syngnathidae) in the Coastal Waters and Local Market of Kota Kinabalu, Sabah, Malaysia.

PubMed

Shapawi, Rossita; Anyie, Adrian Leslie; Hussien, Muhammad Ali Syed; Zuldin, Wahidatul Husna

2015-12-01

Seahorse diversity (genus Hippocampus, Family Syngnathidae), species identification, size composition and sexual dimorphism were studied from November 2012 to March 2013 in selected coastal waters around Kota Kinabalu, Sabah and the local market trade. Six species of seahorses were identified in the study: (1) Hippocampus barbouri, (2) Hippocampus comes, (3) Hippocampus kelloggi, (4) Hippocampus kuda, (5) Hippocampus spinosissimus and (6) Hippocampus trimaculatus. All six species were sold at the local market, and the dried seahorses were obtained mainly by local fishermen using trawl by-catch method and traded as traditional medicine, souvenirs and other uses. Four species were identified by direct samplings in various different habitats of Kota Kinabalu coastal waters: (1) H. barbouri, (2) H. comes, (3) H. kuda, and (4) H. spinosissimus. Based on the results, H. comes was the largest in size among the four fresh/live species found (mean standard length [SL]: 148.25±1.26 mm), whereas H. barbouri was the smallest species (mean SL: 129±7.81 mm). For the dried samples, H. kelloggi was the largest (mean SL: 245.25±14.55 mm) and H. barbouri was the smallest (mean SL: 127.21±10.01 mm). No significant difference (p>0.05) was observed between the lengths of males and females in every seahorse species, and there was no sexual size dimorphism in any of the species. The findings from the study are significant to provide baseline data for the conservation efforts of these unique marine teleost.

Comparison of 2D and 3D wavelet features for TLE lateralization

NASA Astrophysics Data System (ADS)

Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid; Elisevich, Kost; Patel, Suresh

2004-04-01

Intensity and volume features of the hippocampus from MR images of the brain are known to be useful in detecting the abnormality and consequently candidacy of the hippocampus for temporal lobe epilepsy surgery. However, currently, intracranial EEG exams are required to determine the abnormal hippocampus. These exams are lengthy, painful and costly. The aim of this study is to evaluate texture characteristics of the hippocampi from MR images to help physicians determine the candidate hippocampus for surgery. We studied the MR images of 20 epileptic patients. Intracranial EEG results as well as surgery outcome were used as gold standard. The hippocampi were manually segmented by an expert from T1-weighted MR images. Then the segmented regions were mapped on the corresponding FLAIR images for texture analysis. We calculate the average energy features from 2D wavelet transform of each slice of hippocampus as well as the energy features produced by 3D wavelet transform of the whole hippocampus volume. The 2D wavelet transform is calculated both from the original slices as well as from the slices perpendicular to the principal axis of the hippocampus. In order to calculate the 3D wavelet transform we first rotate each hippocampus to fit it in a rectangular prism and then fill the empty area by extrapolating the intensity values. We combine the resulting features with volume feature and compare their ability to distinguish between normal and abnormal hippocampi using linear classifier and fuzzy c-means clustering algorithm. Experimental results show that the texture features can correctly classify the hippocampi.

Multi-scale hippocampal parcellation improves atlas-based segmentation accuracy

NASA Astrophysics Data System (ADS)

Plassard, Andrew J.; McHugo, Maureen; Heckers, Stephan; Landman, Bennett A.

2017-02-01

Known for its distinct role in memory, the hippocampus is one of the most studied regions of the brain. Recent advances in magnetic resonance imaging have allowed for high-contrast, reproducible imaging of the hippocampus. Typically, a trained rater takes 45 minutes to manually trace the hippocampus and delineate the anterior from the posterior segment at millimeter resolution. As a result, there has been a significant desire for automated and robust segmentation of the hippocampus. In this work we use a population of 195 atlases based on T1-weighted MR images with the left and right hippocampus delineated into the head and body. We initialize the multi-atlas segmentation to a region directly around each lateralized hippocampus to both speed up and improve the accuracy of registration. This initialization allows for incorporation of nearly 200 atlases, an accomplishment which would typically involve hundreds of hours of computation per target image. The proposed segmentation results in a Dice similiarity coefficient over 0.9 for the full hippocampus. This result outperforms a multi-atlas segmentation using the BrainCOLOR atlases (Dice 0.85) and FreeSurfer (Dice 0.75). Furthermore, the head and body delineation resulted in a Dice coefficient over 0.87 for both structures. The head and body volume measurements also show high reproducibility on the Kirby 21 reproducibility population (R2 greater than 0.95, p < 0.05 for all structures). This work signifies the first result in an ongoing work to develop a robust tool for measurement of the hippocampus and other temporal lobe structures.

Evolution of the hippocampus in reptiles and birds.

PubMed

Striedter, Georg F

2016-02-15

Although the hippocampus is structurally quite different among reptiles, birds, and mammals, its function in spatial memory is said to be highly conserved. This is surprising, given that structural differences generally reflect functional differences. Here I review this enigma in some detail, identifying several evolutionary changes in hippocampal cytoarchitecture and connectivity. I recognize a lepidosaurid pattern of hippocampal organization (in lizards, snakes, and the tuatara Sphenodon) that differs substantially from the pattern of organization observed in the turtle/archosaur lineage, which includes crocodilians and birds. Although individual subdivisions of the hippocampus are difficult to homologize between these two patterns, both lack a clear homolog of the mammalian dentate gyrus. The strictly trilaminar organization of the ancestral amniote hippocampus was gradually lost in the lineage leading to birds, and birds expanded the system of intrahippocampal axon collaterals, relative to turtles and lizards. These expanded collateral axon branches resemble the extensive collaterals in CA3 of the mammalian hippocampus but probably evolved independently of them. Additional examples of convergent evolution between birds and mammals are the loss of direct inputs to the hippocampus from the primary olfactory cortex and the general expansion of telencephalic regions that communicate reciprocally with the hippocampus. Given this structural convergence, it seems likely that some similarities in the function of the hippocampus between birds and mammals, notably its role in the ability to remember many different locations without extensive training, likewise evolved convergently. The currently available data do not allow for a strong test of this hypothesis, but the hypothesis itself suggests some promising new research directions. © 2015 Wiley Periodicals, Inc.

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

PubMed Central

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Structural hippocampal anomalies in a schizophrenia population correlate with navigation performance on a wayfinding task.

PubMed

Ledoux, Andrée-Anne; Boyer, Patrice; Phillips, Jennifer L; Labelle, Alain; Smith, Andra; Bohbot, Véronique D

2014-01-01

Episodic memory, related to the hippocampus, has been found to be impaired in schizophrenia. Further, hippocampal anomalies have also been observed in schizophrenia. This study investigated whether average hippocampal gray matter (GM) would differentiate performance on a hippocampus-dependent memory task in patients with schizophrenia and healthy controls. Twenty-one patients with schizophrenia and 22 control participants were scanned with an MRI while being tested on a wayfinding task in a virtual town (e.g., find the grocery store from the school). Regressions were performed for both groups individually and together using GM and performance on the wayfinding task. Results indicate that controls successfully completed the task more often than patients, took less time, and made fewer errors. Additionally, controls had significantly more hippocampal GM than patients. Poor performance was associated with a GM decrease in the right hippocampus for both groups. Within group regressions found an association between right hippocampi GM and performance in controls and an association between the left hippocampi GM and performance in patients. A second analysis revealed that different anatomical GM regions, known to be associated with the hippocampus, such as the parahippocampal cortex, amygdala, medial, and orbital prefrontal cortices, covaried with the hippocampus in the control group. Interestingly, the cuneus and cingulate gyrus also covaried with the hippocampus in the patient group but the orbital frontal cortex did not, supporting the hypothesis of impaired connectivity between the hippocampus and the frontal cortex in schizophrenia. These results present important implications for creating intervention programs aimed at measuring functional and structural changes in the hippocampus in schizophrenia.

Adeno-Associated Viral Vector-Induced Overexpression of Neuropeptide Y Y2 Receptors in the Hippocampus Suppresses Seizures

ERIC Educational Resources Information Center

Woldbye, David P. D.; Angehagen, Mikael; Gotzsche, Casper R.; Elbrond-Bek, Heidi; Sorensen, Andreas T.; Christiansen, Soren H.; Olesen, Mikkel V.; Nikitidou, Litsa; Hansen, Thomas v. O.; Kanter-Schlifke, Irene; Kokaia, Merab

2010-01-01

Gene therapy using recombinant adeno-associated viral vectors overexpressing neuropeptide Y in the hippocampus exerts seizure-suppressant effects in rodent epilepsy models and is currently considered for clinical application in patients with intractable mesial temporal lobe epilepsy. Seizure suppression by neuropeptide Y in the hippocampus is…

Dopaminergic Modulation of the Persistence of One-Trial Hippocampus-Dependent Memory

ERIC Educational Resources Information Center

O'Carroll, Colin M.; Martin, Stephen J.; Sandin, Johan; Frenguelli, Bruno; Morris, Richard G. M.

2006-01-01

The persistence of new memory traces in the hippocampus, encoded following appropriate activation of glutamatergic receptors and the induction of synaptic plasticity, can be influenced by heterosynaptic activation of neuromodulatory brain systems. We therefore investigated the effects of a hippocampus-specific blockade of dopamine D1/D5 receptors…

The Hippocampus Supports Encoding of Between-Domain Associations within Working Memory

ERIC Educational Resources Information Center

Piekema, Carinne; Kessel, Roy P. C.; Rijpkema, Mark; Fernandez, Guillen

2009-01-01

It has been established that the medial temporal lobe, including the hippocampus, is crucial for associative memory. The aim of the current functional magnetic resonance imaging (fMRI) study was to investigate whether the hippocampus is differentially activated for associations between items processed in the same neocortical region (within-domain)…

Recognition Memory and the Hippocampus: A Test of the Hippocampal Contribution to Recollection and Familiarity

ERIC Educational Resources Information Center

Jeneson, Annette; Kirwan, C. Brock; Hopkins, Ramona O.; Wixted, John T.; Squire, Larry R.

2010-01-01

It has been suggested that the hippocampus selectively supports recollection and that adjacent cortex in the medial temporal lobe can support familiarity. Alternatively, it has been suggested that the hippocampus supports both recollection and familiarity. We tested these suggestions by assessing the performance of patients with hippocampal…

Acetylcholine Release in the Hippocampus and Striatum during Place and Response Training

ERIC Educational Resources Information Center

Pych, Jason C.; Chang, Qing; Colon-Rivera, Cynthia; Haag, Renee; Gold, Paul E.

2005-01-01

These experiments examined the release of acetylcholine in the hippocampus and striatum when rats were trained, within single sessions, on place or response versions of food-rewarded mazes. Microdialysis samples of extra-cellular fluid were collected from the hippocampus and striatum at 5-min increments before, during, and after training. These…

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory.

PubMed

Wardlaw, Sarah M; Phan, Trongha X; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R

2014-08-01

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1-/- mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1-/- mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1-/- mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1-/- mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1. © 2014 Wardlaw et al.; Published by Cold Spring Harbor Laboratory Press.

The Necessity of the Hippocampus for Statistical Learning

PubMed Central

Covington, Natalie V.; Brown-Schmidt, Sarah; Duff, Melissa C.

2018-01-01

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 a 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. PMID:29308986

Effects of infrasound on hippocampus-dependent learning and memory in rats and some underlying mechanisms.

PubMed

Yuan, Hua; Long, Hua; Liu, Jing; Qu, Lili; Chen, Jingzao; Mou, Xiang

2009-09-01

To investigate the effect of infrasound on the hippocampus-dependent spatial learning and memory as well as its underlying mechanisms, we measured the changes of cognitive abilities, brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signal transduction pathway and neurogenesis in the hippocampus of rats. The results showed that rats exposed to infrasound of 16 Hz at 130 dB for 14 days exhibited longer escape latency from day 2 and shortened time staying in the quadrant P in Morris water maze (MWM). It was found that mRNA and protein expression levels of hippocampal BDNF and TrkB were significantly decreased in real-time PCR and Western blot, and the number of BrdU-labeled cells in hippocampus was also reduced when compared to control. These results provided novel evidences that the infrasound of a certain exposure parameter can impair hippocampus-dependent learning and memory, in which the downregulation of the neuronal plasticity-related BDNF-TrkB signal pathway and less neurogenesis in hippocampus might be involved.

Effect of taurine on the concentrations of glutamate, GABA, glutamine and alanine in the rat striatum and hippocampus.

PubMed

Molchanova, Svetlana M; Oja, Simos S; Saransaari, Pirjo

2007-01-01

Taurine, a non-protein amino acid, acts as an osmoregulator and inhibitory neuromodulator in the brain. Here we studied the effects of intraperitoneal injections of taurine on the concentrations of glutamate and GABA, and their precursors, glutamine and alanine, in the rat striatum and hippocampus. Injections of 0.25, 0.5 and 1 g/kg taurine led to a gradual increase in taurine tissue concentrations in both hippocampus and striatum. Glutamate and GABA also increased in the hippocampus, but not in the striatum. Glutamine increased and alanine decreased markedly in both brain structures. The results corroborate the neuromodulatory role of taurine in the brain. Taurine administration results in an imbalance in inhibitory and excitatory neurotransmission in the glutamatergic (hippocampus) and GABAergic (striatum) brain structures, affecting more markedly the neurotransmitter precursors.

Unilateral hippocampal inactivation or lesion selectively impairs remote contextual fear memory.

PubMed

Zhou, Heng; Zhou, Qixin; Xu, Lin

2016-10-01

Contextual fear memory depends on the hippocampus, but the role of unilateral hippocampus in this type of memory remains unclear. Herein, pharmacological inactivation or excitotoxic lesions were used to study the role of unilateral hippocampus in the stages of contextual fear memory. The pharmacological experiments revealed that compared with the control groups, unilateral hippocampal blockade did not impair 1-day recent memory following learning, whereas bilateral hippocampal blockade significantly impaired this memory. The lesion experiments showed that compared with the control groups, the formed contextual fear memory was retained for 7 days and that 30-day remote memory was markedly reduced in unilateral hippocampal lesion groups. These results indicate that an intact bilateral hippocampus is required for the formation of remote memory and that unilateral hippocampus is sufficient for recent contextual fear memory.

The hippocampus and visual perception

PubMed Central

Lee, Andy C. H.; Yeung, Lok-Kin; Barense, Morgan D.

2012-01-01

In this review, we will discuss the idea that the hippocampus may be involved in both memory and perception, contrary to theories that posit functional and neuroanatomical segregation of these processes. This suggestion is based on a number of recent neuropsychological and functional neuroimaging studies that have demonstrated that the hippocampus is involved in the visual discrimination of complex spatial scene stimuli. We argue that these findings cannot be explained by long-term memory or working memory processing or, in the case of patient findings, dysfunction beyond the medial temporal lobe (MTL). Instead, these studies point toward a role for the hippocampus in higher-order spatial perception. We suggest that the hippocampus processes complex conjunctions of spatial features, and that it may be more appropriate to consider the representations for which this structure is critical, rather than the cognitive processes that it mediates. PMID:22529794

Neurogenic Effects of Ghrelin on the Hippocampus.

PubMed

Kim, Chanyang; Kim, Sehee; Park, Seungjoon

2017-03-08

Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

Estradiol does not influence strategy choice but place strategy choice is associated with increased cell proliferation in the hippocampus of female rats.

PubMed

Rummel, Julia; Epp, Jonathan R; Galea, Liisa A M

2010-09-01

Adult neurogenesis occurs in the hippocampus of most mammals. While the function of adult hippocampal neurogenesis is not known, there is a relationship between neurogenesis and hippocampus-dependent learning and memory. Ovarian hormones can influence learning and memory and strategy choice. In competitive memory tasks, higher levels of estradiol shift female rats towards the use of the place strategy. Previous studies using a cue-competition paradigm find that 36% of male rats will use a hippocampus-dependent place strategy and place strategy users had lower levels of cell proliferation in the hippocampus. Here, we used the same paradigm to test whether endogenous or exogenous ovarian hormones influence strategy choice in the cue-competition paradigm and whether cell proliferation was related to strategy choice. We tested ovariectomized estradiol-treated (10 microg of estradiol benzoate) or sham-operated female rats on alternating blocks of hippocampus-dependent and hippocampus-independent versions of the Morris water task. Rats were then given a probe session with the platform visible and in a novel location. Preferred strategy was classified as place strategy (hippocampus-dependent) if they swam to the old platform location or cue strategy (hippocampus-independent) if they swam to the visible platform. All groups showed a preference for the cue strategy. However, proestrous rats were more likely to be place strategy users than rats not in proestrus. Female place strategy users had increased cell proliferation in the dentate gyrus compared to cue strategy users. Our study suggests that 78% of female rats chose the cue strategy instead of the place strategy. In summary the present results suggest that estradiol does not shift strategy use in this paradigm and that cell proliferation is related to strategy use with greater cell proliferation seen in place strategy users in female rats. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Functional contributions and interactions between the human hippocampus and subregions of the striatum during arbitrary associative learning and memory

PubMed Central

Mattfeld, Aaron T.; Stark, Craig E. L.

2015-01-01

The hippocampus and striatum are thought to have different functional roles in learning and memory. It is unknown under what experimental conditions their contributions are dissimilar or converge, and the extent to which they interact over the course of learning. In order to evaluate both the functional contributions of as well as the interactions between the human hippocampus and striatum, the present study used high-resolution functional magnetic resonance imaging (fMRI) and variations of a conditional visuomotor associative learning task that either taxed arbitrary associative learning (Experiment 1) or stimulus-response learning (Experiment 2). In the first experiment we observed changes in activity in the hippocampus and anterior caudate that reflect differences between the two regions consistent with distinct computational principles. In the second experiment we observed activity in the putamen that reflected content specific representations during the learning of arbitrary conditional visuomotor associations. In both experiments the hippocampus and ventral striatum demonstrated dynamic functional coupling during the learning of new arbitrary associations, but not during retrieval of well-learned arbitrary associations using control variants of the tasks that did not preferentially tax one system versus the other. These findings suggest that both the hippocampus and subregions of the dorsal striatum contribute uniquely to the learning of arbitrary associations while the hippocampus and ventral striatum interact over the course of learning. PMID:25560298

Development of short-snouted seahorse (Hippocampus hippocampus, L. 1758): osteological and morphological aspects.

PubMed

Novelli, B; Otero-Ferrer, F; Socorro, J A; Caballero, M J; Segade-Botella, A; Molina Domínguez, L

2017-06-01

Information about early development after male release lags behind studies of juveniles and adult seahorses, and newborn seahorses, similar in shape to adults, are considered juveniles or fry. During early life, Hippocampus hippocampus present behavioural (shift in habitat, from planktonic to benthic) and morphological changes; for this reasons, the aims of this study are to define the stage of development of H. hippocampus after they are expelled from the male brood pouch and to establish direct or indirect development through an osteological analysis. The ossification process was studied in 120 individuals, from their release to 30 days after birth. To analyse the osteological development, Alcian Blue-Alizarin Red double staining technique for bone and cartilage was adapted to this species. At birth, H. hippocampus presents a mainly cartilaginous structure that ossifies in approximately 1 month. The bony armour composed of bony rings and plates develops in 10 days. The caudal fin, a structure absent in juveniles and adult seahorses, is present at birth and progressively disappears with age. The absence of adult osteological structure in newborns, like coronet, bony rings and plates, head spines and components allowing tail prehensile abilities, suggests a metamorphosis before the juvenile stage. During the indirect development, the metamorphic stage started inside brood pouch and followed outside and leads up to reconsider the status of H. hippocampus newborns.

Human hippocampus arbitrates approach-avoidance conflict.

PubMed

Bach, Dominik R; Guitart-Masip, Marc; Packard, Pau A; Miró, Júlia; Falip, Mercè; Fuentemilla, Lluís; Dolan, Raymond J

2014-03-03

Animal models of human anxiety often invoke a conflict between approach and avoidance. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus. Efforts to translate these approaches to clinical contexts are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Sex, hormones and neurogenesis in the hippocampus: hormonal modulation of neurogenesis and potential functional implications.

PubMed

Galea, L A M; Wainwright, S R; Roes, M M; Duarte-Guterman, P; Chow, C; Hamson, D K

2013-11-01

The hippocampus is an area of the brain that undergoes dramatic plasticity in response to experience and hormone exposure. The hippocampus retains the ability to produce new neurones in most mammalian species and is a structure that is targeted in a number of neurodegenerative and neuropsychiatric diseases, many of which are influenced by both sex and sex hormone exposure. Intriguingly, gonadal and adrenal hormones affect the structure and function of the hippocampus differently in males and females. Adult neurogenesis in the hippocampus is regulated by both gonadal and adrenal hormones in a sex- and experience-dependent way. Sex differences in the effects of steroid hormones to modulate hippocampal plasticity should not be completely unexpected because the physiology of males and females is different, with the most notable difference being that females gestate and nurse the offspring. Furthermore, reproductive experience (i.e. pregnancy and mothering) results in permanent changes to the maternal brain, including the hippocampus. This review outlines the ability of gonadal and stress hormones to modulate multiple aspects of neurogenesis (cell proliferation and cell survival) in both male and female rodents. The function of adult neurogenesis in the hippocampus is linked to spatial memory and depression, and the present review provides early evidence of the functional links between the hormonal modulation of neurogenesis that may contribute to the regulation of cognition and stress. © 2013 British Society for Neuroendocrinology.

Right-hemispheric dominance of spatial memory in split-brain mice.

PubMed

Shinohara, Yoshiaki; Hosoya, Aki; Yamasaki, Nobuyuki; Ahmed, Hassan; Hattori, Satoko; Eguchi, Megumi; Yamaguchi, Shun; Miyakawa, Tsuyoshi; Hirase, Hajime; Shigemoto, Ryuichi

2012-02-01

Left-right asymmetry of human brain function has been known for a century, although much of molecular and cellular basis of brain laterality remains to be elusive. Recent studies suggest that hippocampal CA3-CA1 excitatory synapses are asymmetrically arranged, however, the functional implication of the asymmetrical circuitry has not been studied at the behavioral level. In order to address the left-right asymmetry of hippocampal function in behaving mice, we analyzed the performance of "split-brain" mice in the Barnes maze. The "split-brain" mice received ventral hippocampal commissure and corpus callosum transection in addition to deprivation of visual input from one eye. In such mice, the hippocampus in the side of visual deprivation receives sensory-driven input. Better spatial task performance was achieved by the mice which were forced to use the right hippocampus than those which were forced to use the left hippocampus. In two-choice spatial maze, forced usage of left hippocampus resulted in a comparable performance to the right counterpart, suggesting that both hippocampal hemispheres are capable of conducting spatial learning. Therefore, the results obtained from the Barnes maze suggest that the usage of the right hippocampus improves the accuracy of spatial memory. Performance of non-spatial yet hippocampus-dependent tasks (e.g. fear conditioning) was not influenced by the laterality of the hippocampus. Copyright © 2010 Wiley Periodicals, Inc.

MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression

PubMed Central

Nelson, P. Austin; Sage, Jennifer R.; Wood, Suzanne C.; Davenport, Christopher M.; Anagnostaras, Stephan G.; Boulanger, Lisa M.

2013-01-01

Memory impairment is a common feature of conditions that involve changes in inflammatory signaling in the brain, including traumatic brain injury, infection, neurodegenerative disorders, and normal aging. However, the causal importance of inflammatory mediators in cognitive impairments in these conditions remains unclear. Here we show that specific immune proteins, members of the major histocompatibility complex class I (MHC class I), are essential for normal hippocampus-dependent memory, and are specifically required for NMDAR-dependent forms of long-term depression (LTD) in the healthy adult hippocampus. In β2m−/−TAP−/−mice, which lack stable cell-surface expression of most MHC class I proteins, NMDAR-dependent LTD in area CA1 of adult hippocampus is abolished, while NMDAR-independent forms of potentiation, facilitation, and depression are unaffected. Altered NMDAR-dependent synaptic plasticity in the hippocampus of β2m−/−TAP−/−mice is accompanied by pervasive deficits in hippocampus-dependent memory, including contextual fear memory, object recognition memory, and social recognition memory. Thus normal MHC class I expression is essential for NMDAR-dependent hippocampal synaptic depression and hippocampus-dependent memory. These results suggest that changes in MHC class I expression could be an unexpected cause of disrupted synaptic plasticity and cognitive deficits in the aging, damaged, and diseased brain. PMID:23959708

Robust hippocampal responsivity during retrieval of consolidated associative memory.

PubMed

Hattori, Shoai; Chen, Lillian; Weiss, Craig; Disterhoft, John F

2015-05-01

A contentious point in memory research is whether or not the hippocampus plays a time-limited role in the consolidation of declarative memories. A widely held view is that declarative memories are initially encoded in the hippocampus, then transferred to the neocortex for long-term storage. Alternate views argue instead that the hippocampus continues to play a role in remote memory recall. These competing theories are largely based on human amnesic and animal lesion/inactivation studies. However, in vivo electrophysiological evidence supporting these views is scarce. Given that other studies examining the role of the hippocampus in remote memory retrieval using lesion and imaging techniques in human and animal models have provided mixed results, it would be particularly useful to gain insight at the in vivo electrophysiological level. Here we report hippocampal single-neuron and theta activity recorded longitudinally during acquisition and remote retrieval of trace eyeblink conditioning. Results from conditioned rabbits were compared to those obtained from yoked pseudo-conditioned control rabbits. Results reveal continued learning-specific hippocampal activity one month after initial acquisition of the task. Our findings yield insight into the normal physiological responses of the hippocampus during memory processes and provide compelling in vivo electrophysiological evidence that the hippocampus is involved in both acquisition and retrieval of consolidated memories. © 2014 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Evidence for Hippocampus-Dependent Contextual Learning at Postnatal Day 17 in the Rat

ERIC Educational Resources Information Center

Foster, Jennifer A.; Burman, Michael A.

2010-01-01

Long-term memory for fear of an environment (contextual fear conditioning) emerges later in development (postnatal day; PD 23) than long-term memory for fear of discrete stimuli (PD 17). As contextual, but not explicit cue, fear conditioning relies on the hippocampus; this has been interpreted as evidence that the hippocampus is not fully…

Role of the Dorsal Hippocampus in Object Memory Load

ERIC Educational Resources Information Center

Sannino, Sara; Russo, Fabio; Torromino, Giulia; Pendolino, Valentina; Calabresi, Paolo; De Leonibus, Elvira

2012-01-01

The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed…

Correlates of Intellectual Ability with Morphology of the Hippocampus and Amygdala in Healthy Adults

ERIC Educational Resources Information Center

Amat, Jose A.; Bansal, Ravi; Whiteman, Ronald; Haggerty, Rita; Royal, Jason; Peterson, Bradley S.

2008-01-01

Several prior imaging studies of healthy adults have correlated volumes of the hippocampus and amygdala with measures of general intelligence (IQ), with variable results. In this study, we assessed correlations between volumes of the hippocampus and amygdala and full-scale IQ scores (FSIQ) using a method of image analysis that permits detailed…

Role of Amygdala and Hippocampus in the Neural Circuit Subserving Conditioned Defeat in Syrian Hamsters

ERIC Educational Resources Information Center

Markham, Chris M.; Taylor, Stacie L.; Huhman, Kim L.

2010-01-01

We examined the roles of the amygdala and hippocampus in the formation of emotionally relevant memories using an ethological model of conditioned fear termed conditioned defeat (CD). Temporary inactivation of the ventral, but not dorsal hippocampus (VH, DH, respectively) using muscimol disrupted the acquisition of CD, whereas pretraining VH…

Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

PubMed

Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

2017-04-01

Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Ying; Li, Jia; Li, Shanshan

2015-07-01

Curcumin is a natural polyphenolic compound in Curcuma longa with beneficial effects on neuronal protection. This study aims to investigate the action of curcumin in the hippocampus subjected to glutamate neurotoxicity. Glutamate stimulation induced reactive oxygen species (ROS), endoplasmic reticulum stress (ER stress) and TXNIP/NLRP3 inflammasome activation, leading to damage in the hippocampus. Curcumin treatment in the hippocampus or SH-SY5Y cells inhibited IRE1α and PERK phosphorylation with suppression of intracellular ROS production. Curcumin increased AMPK activity and knockdown of AMPKα with specific siRNA abrogated its inhibitory effects on IRE1α and PERK phosphorylation, indicating that AMPK activity was essential for themore » suppression of ER stress. As a result, curcumin reduced TXNIP expression and inhibited NLRP3 inflammasome activation by downregulation of NLRP3 and cleaved caspase-1 induction, and thus reduced IL-1β secretion. Specific fluorescent probe and flow cytometry analysis showed that curcumin prevented mitochondrial malfunction and protected cell survival from glutamate neurotoxicity. Moreover, oral administration of curcumin reduced brain infarct volume and attenuated neuronal damage in rats subjected to middle cerebral artery occlusion. Immunohistochemistry showed that curcumin inhibited p-IRE1α, p-PERK and NLRP3 expression in hippocampus CA1 region. Together, these results showed that curcumin attenuated glutamate neurotoxicity by inhibiting ER stress-associated TXNIP/NLRP3 inflammasome activation via the regulation of AMPK, and thereby protected the hippocampus from ischemic insult. - Highlights: • Curcumin attenuates glutamate neurotoxicity in the hippocampus. • Curcumin suppresses ER stress in glutamate-induced hippocampus slices. • Curcumin inhibits TXNIP/NLRP3 inflammasome activation. • Regulation of AMPK by curcumin contributes to suppressing ER stress.« less

Effects of acute and chronic methamphetamine administration on cynomolgus monkey hippocampus structure and cellular transcriptome.

PubMed

Choi, Mi Ran; Chun, Ji-Won; Kwak, Su Min; Bang, Sol Hee; Jin, Yeung-Bae; Lee, Youngjeon; Kim, Han-Na; Chang, Kyu-Tae; Chai, Young Gyu; Lee, Sang-Rae; Kim, Dai-Jin

2018-05-23

Methamphetamine (MA), a psychostimulant abused worldwide, gives rise to neurotoxicity in the hippocampus, resulting in cognitive impairments and hippocampal volume reduction. The cellular and molecular mechanisms associated with hippocampal impairments due to MA remain unknown. The aim of this study was to investigate the effects of MA on structural alterations and gene expressions in the hippocampus. We analyzed the pattern of volumetric changes in the hippocampus using magnetic resonance imaging (MRI) after acute and chronic administration of MA to cynomolgus macaques. In addition, we performed large-scale transcriptome profiling in the hippocampus using RNA-Seq technology. The hippocampus in response to acute and chronic MA exhibited a significant volumetric atrophy compared with the hippocampus of controls. The genes associated with cytoskeleton organization and phagocytosis were downregulated in the acute MA-treated group compared to the control group. On the other hand, genes associated with synaptic transmission, regulation of neuron differentiation and regulation of neurogenesis were downregulated in the chronic MA-treated group. We confirmed that expression patterns for ADM, BMP4, CHRD, PDYN, UBA1, profilin 2 (PFN2), ENO2 and NSE mRNAs were similar to the results from RNA-Seq based on quantitative RT-PCR. In particular, PFN2 mRNA and protein expression levels, which play important roles in actin cytoskeleton dynamics, were decreased by acute and chronic MA administration. These results not only aid the understanding of cellular and molecular mechanisms regulated by MA in the hippocampus but also suggest basic information aiding biomarker and novel drug development for treating hippocampal impairment caused by MA abuse. Copyright © 2017. Published by Elsevier Inc.

Long-term aerobic exercise increases redox-active iron through nitric oxide in rat hippocampus.

PubMed

Chen, Qian; Xiao, De-Sheng

2014-01-30

Adult hippocampus is highly vulnerable to iron-induced oxidative stress. Aerobic exercise has been proposed to reduce oxidative stress but the findings in the hippocampus are conflicting. This study aimed to observe the changes of redox-active iron and concomitant regulation of cellular iron homeostasis in the hippocampus by aerobic exercise, and possible regulatory effect of nitric oxide (NO). A randomized controlled study was designed in the rats with swimming exercise treatment (for 3 months) and/or an unselective inhibitor of NO synthase (NOS) (L-NAME) treatment. The results from the bleomycin-detectable iron assay showed additional redox-active iron in the hippocampus by exercise treatment. The results from nonheme iron content assay, combined with the redox-active iron content, showed increased storage iron content by exercise treatment. NOx (nitrate plus nitrite) assay showed increased NOx content by exercise treatment. The results from the Western blot assay showed decreased ferroportin expression, no changes of TfR1 and DMT1 expressions, increased IRP1 and IRP2 expression, increased expressions of eNOS and nNOS rather than iNOS. In these effects of exercise treatment, the increased redox-active iron content, storage iron content, IRP1 and IRP2 expressions were completely reversed by L-NAME treatment, and decreased ferroportin expression was in part reversed by L-NAME. L-NAME treatment completely inhibited increased NOx and both eNOS and nNOS expression in the hippocampus. Our findings suggest that aerobic exercise could increase the redox-active iron in the hippocampus, indicating an increase in the capacity to generate hydroxyl radicals through the Fenton reactions, and aerobic exercise-induced iron accumulation in the hippocampus might mainly result from the role of the endogenous NO. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional relationships between the hippocampus and dorsomedial striatum in learning a visual scene-based memory task in rats.

PubMed

Delcasso, Sébastien; Huh, Namjung; Byeon, Jung Seop; Lee, Jihyun; Jung, Min Whan; Lee, Inah

2014-11-19

The hippocampus is important for contextual behavior, and the striatum plays key roles in decision making. When studying the functional relationships with the hippocampus, prior studies have focused mostly on the dorsolateral striatum (DLS), emphasizing the antagonistic relationships between the hippocampus and DLS in spatial versus response learning. By contrast, the functional relationships between the dorsomedial striatum (DMS) and hippocampus are relatively unknown. The current study reports that lesions to both the hippocampus and DMS profoundly impaired performance of rats in a visual scene-based memory task in which the animals were required to make a choice response by using visual scenes displayed in the background. Analysis of simultaneous recordings of local field potentials revealed that the gamma oscillatory power was higher in the DMS, but not in CA1, when the rat performed the task using familiar scenes than novel ones. In addition, the CA1-DMS networks increased coherence at γ, but not at θ, rhythm as the rat mastered the task. At the single-unit level, the neuronal populations in CA1 and DMS showed differential firing patterns when responses were made using familiar visual scenes than novel ones. Such learning-dependent firing patterns were observed earlier in the DMS than in CA1 before the rat made choice responses. The present findings suggest that both the hippocampus and DMS process memory representations for visual scenes in parallel with different time courses and that flexible choice action using background visual scenes requires coordinated operations of the hippocampus and DMS at γ frequencies. Copyright © 2014 the authors 0270-6474/14/3415534-14$15.00/0.

Oxidative stress-induced cognitive impairment in obesity can be reversed by vitamin D administration in rats.

PubMed

Hajiluian, Ghazaleh; Abbasalizad Farhangi, Mahdieh; Nameni, Ghazaleh; Shahabi, Parviz; Megari-Abbasi, Mehran

2017-07-06

There is evidence that obesity leads to cognitive impairments via several markers of oxidative stress including glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in the hippocampus. Increased inflammatory markers in the brain have obesity triggering effects. In the current study we aimed to investigate the effects of vitamin D on cognitive function, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α concentration and markers of oxidative stress in the hippocampus of high-fat diet-induced obese rats. Forty male Wistar rats were divided into two groups: control diet (CD) and high-fat diet (HFD) for 16 weeks; then each group subdivided into two groups including: CD, CD + vitamin D, HFD and HFD + vitamin D. Vitamin D was administered at 500 IU/kg dosage for 5 weeks. Four weeks after supplementation, Morris water maze test was performed. NF-κB and TNF-α concentration in the hippocampus were determined using ELISA kits. Moreover, oxidative stress markers in the hippocampus including GPx, SOD, MDA and CAT concentrations were measured by spectrophotometry methods. HFD significantly increased TNF-α (P = 0.04) and NF-κB (P = 0.01) concentrations in the hippocampus compared with CD. Vitamin D treatment led to a significant reduction in hippocampus NF-κB concentrations in HFD + vitamin D group (P = 0.001); however, vitamin D had no effect on TNF-α concentrations. Moreover, HFD significantly induced oxidative stress by reducing GPx, SOD and increasing MDA concentrations in the hippocampus. Vitamin D supplementation in HFD group also significantly increased GPx, SOD and reduced MDA concentrations. Vitamin D improved hippocampus oxidative stress and inflammatory markers in HFD-induced obese rats and improved cognitive performance. Further studies are needed to better clarify the underlying mechanisms.

Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

PubMed

Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

2017-08-01

We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

PubMed

Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

2016-03-01

Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus.

PubMed

Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

2014-08-01

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions.

Neuroprotective effect of pretreatment with ganoderma lucidum in cerebral ischemia/reperfusion injury in rat hippocampus

PubMed Central

Zhang, Wangxin; Zhang, Quiling; Deng, Wen; Li, Yalu; Xing, Guoqing; Shi, Xinjun; Du, Yifeng

2014-01-01

Ganoderma lucidum is a traditional Chinese medicine, which has been shown to have both anti-oxidative and anti-inflammatory effects, and noticeably decreases both the infarct area and neuronal apoptosis of the ischemic cortex. This study aimed to investigate the protective effects and mechanisms of pretreatment with ganoderma lucidum (by intragastric administration) in cerebral ischemia/reperfusion injury in rats. Our results showed that pretreatment with ganoderma lucidum for 3 and 7 days reduced neuronal loss in the hippocampus, diminished the content of malondialdehyde in the hippocampus and serum, decreased the levels of tumor necrosis factor-α and interleukin-8 in the hippocampus, and increased the activity of superoxide dismutase in the hippocampus and serum. These results suggest that pretreatment with ganoderma lucidum was protective against cerebral ischemia/reperfusion injury through its anti-oxidative and anti-inflammatory actions. PMID:25317156

Hippocampus in the N. American mink (Mustela vison Brisson, 1756).

PubMed

Gościcka, D; Stankiewicz, W; Szpinda, M

1993-01-01

In sixty adult minks the hippocampus was dissected and measurements of its individual components were taken. Anatomical studies of the mink have been hardly undertaken, while the studies of the mink's brain can be considered as "terra incognita" (D. Gościcka). This is why it was decided to conduct an examination of the hippocampus of this animal.

Long-Term Memory for Place Learning Is Facilitated by Expression of cAMP Response Element-Binding Protein in the Dorsal Hippocampus

ERIC Educational Resources Information Center

Brightwell, Jennifer J.; Smith, Clayton A.; Neve, Rachael L.; Colombo, Paul J.

2007-01-01

Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in…

Contributions of Volumetrics of the Hippocampus and Thalamus to Verbal Memory in Temporal Lobe Epilepsy Patients

ERIC Educational Resources Information Center

Stewart, Christopher C.; Griffith, H. Randall; Okonkwo, Ozioma C.; Martin, Roy C.; Knowlton, Robert K.; Richardson, Elizabeth J.; Hermann, Bruce P.; Seidenberg, Michael

2009-01-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However,…

Hippocampus in health and disease: An overview

PubMed Central

Anand, Kuljeet Singh; Dhikav, Vikas

2012-01-01

Hippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders. In last decade or so, lot has been learnt about conditions that affect hippocampus and produce changes ranging from molecules to morphology. Progresses in radiological delineation, electrophysiology, and histochemical characterization have made it possible to study this archicerebral structure in greater detail. Present paper attempts to give an overview of hippocampus, both in health and diseases. PMID:23349586

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

PubMed

Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Neurosteroids in Adult Hippocampus of Male and Female Rodents: Biosynthesis and Actions of Sex Steroids.

PubMed

Hojo, Yasushi; Kawato, Suguru

2018-01-01

The brain is not only the target of steroid hormones but also is able to locally synthesize steroids de novo . Evidence of the local production of steroids in the brain has been accumulating in various vertebrates, including teleost fish, amphibia, birds, rodents, non-human primates, and humans. In this review, we mainly focus on the local production of sex steroids in the hippocampal neurons of adult rodents (rats and mice), a center for learning and memory. From the data of the hippocampus of adult male rats, hippocampal principal neurons [pyramidal cells in CA1-CA3 and granule cells in dentate gyrus (DG)] have a complete system for biosynthesis of sex steroids. Liquid chromatography with tandem-mass-spectrometry (LC-MS/MS) enabled us to accurately determine the levels of hippocampal sex steroids including 17β-estradiol (17β-E2), testosterone (T), and dihydrotestosterone (DHT), which are much higher than those in blood. Next, we review the steroid synthesis in the hippocampus of female rats, since previous knowledge had been biased toward the data from males. Recently, we clarified that the levels of hippocampal steroids fluctuate in adult female rats across the estrous cycle. Accurate determination of hippocampal steroids at each stage of the estrous cycle is of importance for providing the account for the fluctuation of female hippocampal functions, including spine density, long-term potentiation (LTP) and long-term depression (LTD), and learning and memory. These functional fluctuations in female had been attributed to the level of circulation-derived steroids. LC-MS/MS analysis revealed that the dendritic spine density in CA1 of adult female hippocampus correlates with the levels of hippocampal progesterone and 17β-E2. Finally, we introduce the direct evidence of the role of hippocampus-synthesized steroids in hippocampal function including neurogenesis, LTP, and memory consolidation. Mild exercise (2 week of treadmill running) elevated synthesis of DHT in the hippocampus, but not in the testis, of male rats, resulting in enhancement of neurogenesis in DG. Concerning synaptic plasticity, hippocampus-synthesized E2 is required for LTP induction, whereas hippocampus-synthesized DHT is required for LTD induction. Furthermore, hippocampus-synthesized E2 is involved in memory consolidation tested by object recognition and object placement tasks, both of which are hippocampus-dependent.

Identifying and Characterizing the Effects of Nutrition on Hippocampal Memory123

PubMed Central

Monti, Jim M.; Baym, Carol L.; Cohen, Neal J.

2014-01-01

In this review we provide evidence linking relational memory to the hippocampus, as well as examples of sensitive relational memory tasks that may help characterize the subtle effects of nutrition on learning and memory. Research into dietary effects on cognition is in its nascent stages, and many studies have cast a wide net with respect to areas of cognition to investigate. However, it may be that nutrition will have a disproportionate effect on particular cognitive domains. Thus, researchers interested in nutrition-cognition interactions may wish to apply a more targeted approach when selecting cognitive domains. We suggest that hippocampus-based relational memory may be extraordinarily sensitive to the effects of nutrition. The hippocampus shows unique plastic capabilities, making its structure and function responsive to an array of lifestyle factors and environmental conditions, including dietary intake. A major function of the hippocampus is relational memory, defined as learning and memory for the constituent elements and facts that comprise events. Here we identify several sensitive tests of relational memory that may be used to examine what may be subtle effects of nutrition on hippocampus and memory. We then turn to the literature on aerobic exercise and cognition to provide examples of translational research programs that have successfully applied this targeted approach centering on the hippocampus and sensitive relational memory tools. Finally, we discuss selected findings from animal and human research on nutrition and the hippocampus and advocate for the role of relational memory tasks in future research. PMID:24829486

Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats.

PubMed

Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong

2017-01-01

Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT 4 ) administration increased the level of free triiodothyronine (FT 3 ) and free tetraiodothyroxine (FT 4 ) not only in serum but also in hippocampus. In addition, a single systemic LT 4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT 4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT 4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT 4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT 4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT 4 did not affect rats' locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders.

Hippocampal shape deformation in female patients with unremitting major depressive disorder.

PubMed

Tae, W S; Kim, S S; Lee, K U; Nam, E C; Choi, J W; Park, J I

2011-04-01

The hippocampal atrophy of MDD has been known, but the region shape contractions of the hippocampus in MDD were inconsistent. Spheric harmonic shape analysis was applied to the hippocampus in female patients with unremitting MDD to evaluate morphometric changes of the hippocampus. Shape analysis was performed by using T1-weighted MR imaging in 21 female patients with MDD and 21 age- and sex-matched healthy controls. Manually segmented hippocampi were parameterized, and the point-to-point-based group difference was compared by using the Hotelling T-squared test. The partial correlation analyses were tested between clinical variables and shape changes. Both hippocampal volumes were small in patients with MDD compared with healthy controls, and the right hippocampal volume was negatively correlated with the number of episodes at marginal significance. Regional shape contractions were found in the ambient gyrus, basal hippocampal head, posterior subiculum, and dorsal hippocampus of the left hemisphere. The right hippocampus showed a similar pattern but was less atrophic compared with the left hippocampus. A negative correlation was found between the HDRS and shape deformation in the CA3, ambient gyrus, posterior subiculum, and gyrus fasciolaris of the left hippocampus. We showed atrophy and regional shape contractions in the hippocampi of patients with MDD, which were more dominant on the left side. The causes of hippocampal damage could be the hypersecretion of glucocorticoids contributing to neuronal death or the failing of adult neurogenesis in the dentate gyrus.

Characterizing the role of the hippocampus during episodic simulation and encoding.

PubMed

Thakral, Preston P; Benoit, Roland G; Schacter, Daniel L

2017-12-01

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior-posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation-related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval. © 2017 Wiley Periodicals, Inc.

Volumetric and morphological characteristics of the hippocampus are associated with progression to schizophrenia in patients with first-episode psychosis.

PubMed

Sauras, R; Keymer, A; Alonso-Solis, A; Díaz, A; Molins, C; Nuñez, F; Rabella, M; Roldán, A; Grasa, E; Alvarez, E; Portella, M J; Corripio, I

2017-09-01

Abnormalities in the hippocampus have been implicated in the pathophysiology of psychosis. However, it is still unclear whether certain abnormalities are a pre-existing vulnerability factor, a sign of disease progression or a consequence of environmental factors. We hypothesized that first-episode psychosis patients who progress to schizophrenia after one year of follow up will display greater volumetric and morphological changes from the very beginning of the disorder. We studied the hippocampus of 41 patients with a first-episode psychosis and 41 matched healthy controls. MRI was performed at the time of the inclusion in the study. After one year, the whole sample was reevaluated and divided in two groups depending on the diagnoses (schizophrenia vs. non-schizophrenia). Patients who progressed to schizophrenia showed a significantly smaller left hippocampus volume than control group and no-schizophrenia group (F=3.54; df=2, 77; P=0.03). We also found significant differences in the morphology of the anterior hippocampus (CA1) of patients with first-episode psychosis who developed schizophrenia compared with patients who did not. These results are consistent with the assumption of hyperfunctioning dopaminergic cortico-subcortical circuits in schizophrenia, which might be related with an alteration of subcortical structures, such as the hippocampus, along the course of the disease. According with these results, hippocampus abnormalities may serve as a prognostic marker of clinical outcome in patients with a first-episode psychosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

PubMed

Barbeau, Emmanuel J; Chauvel, Patrick; Moulin, Christopher J A; Regis, Jean; Liégeois-Chauvel, Catherine

2017-04-01

The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Hippocampal Administration of Levothyroxine Impairs Contextual Fear Memory Consolidation in Rats

PubMed Central

Yu, Dafu; Zhou, Heng; Zou, Lin; Jiang, Yong; Wu, Xiaoqun; Jiang, Lizhu; Zhou, Qixin; Yang, Yuexiong; Xu, Lin; Mao, Rongrong

2017-01-01

Thyroid hormone (TH) receptors are highly distributed in the hippocampus, which plays a vital role in memory processes. However, how THs are involved in the different stages of memory process is little known. Herein, we used hippocampus dependent contextual fear conditioning to address the effects of hippocampal THs on the different stages of fear memory. First, we found that a single systemic levothyroxine (LT4) administration increased the level of free triiodothyronine (FT3) and free tetraiodothyroxine (FT4) not only in serum but also in hippocampus. In addition, a single systemic LT4 administration immediately after fear conditioning significantly impaired fear memory. These results indicated the important role of hippocampal THs in fear memory process. To further confirm the effects of hippocampal THs on the different stages of fear memory, LT4 (0.4 μg/μl, 1 μl/side) was injected bilaterally into hippocampus. Rats given LT4 into hippocampus before training or tests had no effect on the acquisition or retrieval of fear memory, however rats given LT4 into hippocampus either immediately or 2 h after training showed being significantly impaired fear memory, which demonstrated LT4 administration into hippocampus impairs the consolidation but has no effect on the acquisition and retrieval of fear memory. Furthermore, hippocampal injection of LT4 did not affect rats’ locomotor activity, thigmotaxis and THs level in prefrontal cortex (PFC) and serum. These findings may have important implications for understanding mechanisms underlying contribution of THs to memory disorders. PMID:28824379

Adult neurogenesis is reduced in the dorsal hippocampus of rats displaying learned helplessness behavior.

PubMed

Ho, Y C; Wang, S

2010-11-24

Clinical and preclinical studies suggest that the hippocampus has a role in the pathophysiology of major depression. In the learned helplessness (LH) animal model of depression after inescapable shocks (ISs) animals that display LH behavior have reduced cell proliferation in the hippocampus; this effect can be reversed by antidepressant treatment. Using this model, we compared rats that displayed LH behavior and rats that did not show LH behavior (NoLH) after ISs to determine whether reduced hippocampal cell proliferation is associated with the manifestation of LH behavior or is a general response to stress. Specifically, we examined cell proliferation, neurogenesis, and synaptic function in dorsal and ventral hippocampus of LH and NoLH animals and control rats that were not shocked. The LH rats had showed reduced cell proliferation, neurogenesis, and synaptic transmission in the dorsal hippocampus, whereas no changes were seen in the ventral hippocampus. These changes were not observed in the NoLH animals. In a group of NoLH rats that received the same amount of electrical shock as the LH rats to control for the unequal shocks received in these two groups, we observed changes in Ki-67(+) cells associated with acute stress. We conclude that reduced hippocampal cell proliferation and neurogenesis are associated with the manifestation of LH behavior and that the dorsal hippocampus is the most affected area. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Directional coupling from the olfactory bulb to the hippocampus during a go/no-go odor discrimination task.

PubMed

Gourévitch, Boris; Kay, Leslie M; Martin, Claire

2010-05-01

The hippocampus and olfactory regions are anatomically close, and both play a major role in memory formation. However, the way they interact during odor processing is still unclear. In both areas, strong oscillations of the local field potential (LFP) can be recorded, and are modulated by behavior. In particular, in the olfactory system, the beta rhythm (15-35 Hz) is associated with cognitive processing of an olfactory stimulus. Using LFP recordings in the olfactory bulb and dorsal and ventral hippocampus during performance of an olfactory go/no-go task in rats, we previously showed that beta oscillations are also present in the hippocampus, coherent with those in the olfactory bulb, during odor sampling. In this study, we provide further insight into information transfer in the olfacto-hippocampal network by using directional coherence (DCOH estimate), a method based on the temporal relation between two or more signals in the frequency domain. In the theta band (6-12 Hz), coherence between the olfactory bulb (OB) and the hippocampus (HPC) is weak and can be both in the feedback and feedforward directions. However, at this frequency, modulation of the coupling between the dorsal and ventral hippocampus is seen during stimulus expectation versus odor processing. In the beta frequency band (15-35 Hz), analysis showed a strong unidirectional coupling from the OB to dorsal and ventral HPC, indicating that, during odor processing, beta oscillations in the hippocampus are driven by the olfactory bulb.

A Distributed Representation of Remembered Time

DTIC Science & Technology

2015-11-19

hippocampus , time, and memory across scales. Journal of Experimental Psychology: General., 142(4), 1211-30. doi: 10.1037/a0033621 Howard, M. W...The hippocampus , time, and memory across scales. Journal of Experimental Psychology: General., 142(4), 1211-30. doi: 10.1037/a0033621 Howard, M. W...accomplished this goal by developing a computational framework that describes a wide range of functional cellular correlates in the hippocampus and

[Activation of autophagy pathway in hippocampus and deterioration of learning and memory ability by intermittent hypoxia in rats after cerebral ischemia].

PubMed

Guo, Xiangfei; Zhao, Yaning; Li, Jianmin; Liu, Wenqian; Chen, Changxiang

2016-09-01

Objective To investigate the effects of different duration of intermittent hypoxia on the autophagy pathway in the hippocampus and the learning and memory ability after cerebral ischemia in rats. Methods 100 male Wistar rats were randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R) group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7-I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion (IH14-I/R) group, intermittent hypoxia for 21 days combined with ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R group, IH14-I/R group and IH21-I/R group were respectively subjected to intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells in the hippocampus of rat brain were detected by HE staining; the levels of mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were determined by quantitative real-time PCR; the distribution of mTOR and beclin 1 in the hippocampus was observed by immunohistochemistry; the learning and memory ability of rats was assessed by the Morris water maze test. Results Compared with the SO group, the never cell morphology was damaged, the number of survival neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in the hippocampus were strengthened, and the learning and memory ability declined in the I/R group. Compared with the I/R group, the never cell morphology was damaged seriously, the number of survival neurons in the hippocampus decreased, the expressions of mTOR and beclin 1 in the hippocampus increased, and the learning and memory ability dropped in the intermittent hypoxia groups. What's more, the above changes were dependent on the duration of intermittent hypoxia. Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory after cerebral ischemia and the damages increase with time passing, which are related to mTOR-beclin 1 activation and increasing neuronal cell death.

Vasopressin V1 receptor in rat hippocampus is regulated by adrenocortical functions.

PubMed

Saito, R; Ishiharada, N; Ban, Y; Honda, K; Takano, Y; Kamiya, H

1994-05-16

Two subtypes of arginine vasopressin (AVP) receptors (V1 and V2) have been distinguished. In this study, we examined the characteristics of AVP binding in rat hippocampus and the effects of bilateral adrenalectomy and adrenal steroids on its [3H]AVP binding. [3H]AVP binding to rat liver and the hippocampal membranes was strongly inhibited by the V1 antagonist, OPC-21268. ADX resulted in a significant decrease in the Bmax of AVP binding in the hippocampus. Chronic treatment with aldosterone and corticosterone restored the ADX-induced reduction, but treatment with dexamethasone did not. These results suggest that the AVP V1 receptor in the hippocampus is regulated by adrenocortical neuroregulatory functions.

[Changes in proline-specific peptidase activity in experimental model of retrograde amnesia].

PubMed

Nazarova, G A; Zolotov, N N; Krupina, N A; Kraĭneva, V A; Garibova, T L; Voronina, T A

2007-01-01

Changes in proline-specific peptidase activity in the frontal cortex and hippocampus were studied using the experimental model of retrograde amnesia in rats. In one group, the amnesia was produced by a single injection of M-cholinergic antagonist scopolamine and the other group received the maximal electroconvulsive stimulation (MES). The amnesic effect was evaluated in passive avoidance test. In the amnesia models under consideration, the activity of prolylendopeptidase was significantly increased in both frontal cortex and hippocampus. The activity of dipeptidyl peptidase IV was significantly decreased in the cortex, whereas in the hippocampus it remained unchanged. Pyracetam inhibited prolylendopeptidase in the cortex and hippocampus, whereas dipeptidyl peptidase IV activity remained unchanged.

An event map of memory space in the hippocampus

PubMed Central

Deuker, Lorena; Bellmund, Jacob LS; Navarro Schröder, Tobias; Doeller, Christian F

2016-01-01

The hippocampus has long been implicated in both episodic and spatial memory, however these mnemonic functions have been traditionally investigated in separate research strands. Theoretical accounts and rodent data suggest a common mechanism for spatial and episodic memory in the hippocampus by providing an abstract and flexible representation of the external world. Here, we monitor the de novo formation of such a representation of space and time in humans using fMRI. After learning spatio-temporal trajectories in a large-scale virtual city, subject-specific neural similarity in the hippocampus scaled with the remembered proximity of events in space and time. Crucially, the structure of the entire spatio-temporal network was reflected in neural patterns. Our results provide evidence for a common coding mechanism underlying spatial and temporal aspects of episodic memory in the hippocampus and shed new light on its role in interleaving multiple episodes in a neural event map of memory space. DOI: http://dx.doi.org/10.7554/eLife.16534.001 PMID:27710766

Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus.

PubMed

Foffani, Guglielmo; Uzcategui, Yoryani G; Gal, Beatriz; Menendez de la Prida, Liset

2007-09-20

Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge from a disorganized ripple pattern caused by unreliable firing in the epileptic hippocampus. Enhanced synaptic activity is responsible for the irregular bursting of CA3 pyramidal cells due to large membrane potential fluctuations. Lower field interactions and a reduced spike-timing reliability concur with decreased spatial synchronization and the emergence of fast ripples. Reducing synaptically driven membrane potential fluctuations improves both spike-timing reliability and spatial synchronization and restores ripples in the epileptic hippocampus. Conversely, a lower spike-timing reliability, with reduced potassium currents, is associated with ripple shuffling in normal hippocampus. Therefore, fast ripples may reflect a pathological desynchronization of the normal ripple pattern.

Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

PubMed

Hescham, Sarah; Jahanshahi, Ali; Schweimer, Judith V; Mitchell, Stephen N; Carter, Guy; Blokland, Arjan; Sharp, Trevor; Temel, Yasin

2016-11-01

Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

Reward-Based Learning Drives Rapid Sensory Signals in Medial Prefrontal Cortex and Dorsal Hippocampus Necessary for Goal-Directed Behavior.

PubMed

Le Merre, Pierre; Esmaeili, Vahid; Charrière, Eloïse; Galan, Katia; Salin, Paul-A; Petersen, Carl C H; Crochet, Sylvain

2018-01-03

The neural circuits underlying learning and execution of goal-directed behaviors remain to be determined. Here, through electrophysiological recordings, we investigated fast sensory processing across multiple cortical areas as mice learned to lick a reward spout in response to a brief deflection of a single whisker. Sensory-evoked signals were absent from medial prefrontal cortex and dorsal hippocampus in naive mice, but developed with task learning and correlated with behavioral performance in mice trained in the detection task. The sensory responses in medial prefrontal cortex and dorsal hippocampus occurred with short latencies of less than 50 ms after whisker deflection. Pharmacological and optogenetic inactivation of medial prefrontal cortex or dorsal hippocampus impaired behavioral performance. Neuronal activity in medial prefrontal cortex and dorsal hippocampus thus appears to contribute directly to task performance, perhaps providing top-down control of learned, context-dependent transformation of sensory input into goal-directed motor output. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Prolactin system in the hippocampus.

PubMed

Carretero, José; Sánchez-Robledo, Virginia; Carretero-Hernández, Marta; Catalano-Iniesta, Leonardo; García-Barrado, María José; Iglesias-Osma, María Carmen; Blanco, Enrique J

2018-05-28

Among the more than 300 biological actions described for prolactin, its role in the neurogenic capacity of the hippocampus, which increases synaptogenesis and neuronal plasticity, consolidates memory and acts as a neuronal protector against excitotoxicity-effects mediated through its receptors are more recently known. The detection of prolactin in the hippocampus and its receptors, specifically in the Ammon's horn and dentate gyrus, opened up a new field of study on the possible neuroprotective effect of hormones in a structure involved in learning and memory, as well as in emotional and behavioral processes. It is currently known, although controversial, that prolactin may be related to sex and age and that the hormone could be synthesized in the hippocampus itself. However, the regulatory mechanisms of changes in prolactin or in its hippocampal receptors still remain unknown. This review introduces the reader to general aspects concerning prolactin and its receptors and to what is currently known about the role prolactin plays in the brain and, in particular, in the hippocampus.

Alternative conceptions of memory consolidation and the role of the hippocampus at the systems level in rodents.

PubMed

Sutherland, R J; Lehmann, H

2011-06-01

We discuss very recent experiments with rodents addressing the idea that long-term memories initially depending on the hippocampus, over a prolonged period, become independent of it. No unambiguous recent evidence exists to substantiate that this occurs. Most experiments find that recent and remote memories are equally affected by hippocampus damage. Nearly all experiments that report spared remote memories suffer from two problems: retrieval could be based upon substantial regions of spared hippocampus and recent memory is tested at intervals that are of the same order of magnitude as cellular consolidation. Accordingly, we point the way beyond systems consolidation theories, both the Standard Model of Consolidation and the Multiple Trace Theory, and propose a simpler multiple storage site hypothesis. On this view, with event reiterations, different memory representations are independently established in multiple networks. Many detailed memories always depend on the hippocampus; the others may be established and maintained independently. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of Pharmacologic and Genetic Inhibition of Alk on Cognitive Impairments in NF1 Mutant Mice

DTIC Science & Technology

2016-08-01

impairments. 15. SUBJECT TERMS cognitive performance, pharmacological inhibition, spatial memory , hippocampus 16. SECURITY CLASSIFICATION OF: 17...mouse model; hippocampus ; pharmacological inhibition; spatial memory 2 ACCOMPLISHMENTS: ▪ Major goals of the project Specific Aim (months 1-24...speeds seen in the water maze (Fig. 2). Contextual fear learning and memory Next the mice were tested for acquisition and extinction of hippocampus

Glucose Injections into the Dorsal Hippocampus or Dorsolateral Striatum of Rats Prior to T-Maze Training: Modulation of Learning Rates and Strategy Selection

ERIC Educational Resources Information Center

Canal, Clinton E.; Stutz, Sonja J.; Gold, Paul E.

2005-01-01

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial…

Dorsal hippocampal N-methyl-D-aspartate receptors underlie spatial working memory performance during non-matching to place testing on the T-maze.

PubMed

McHugh, Stephen B; Niewoehner, Burkhard; Rawlins, J N P; Bannerman, David M

2008-01-10

Previous lesion studies have suggested a functional dissociation along the septotemporal axis of the hippocampus. Whereas the dorsal hippocampus has been implicated in spatial memory processes, the ventral hippocampus may play a role in anxiety. However, these lesion studies are potentially confounded by demyelination of fibres passing through the lesion site, and the possibility of secondary, downstream changes in associated brain structures as a consequence of their chronic denervation following the lesion. In the present study, we have used the microinfusion of muscimol to temporarily inactivate either the dorsal or ventral hippocampus in order to re-examine the contribution of the hippocampal sub-regions to spatial memory. Microinfusion studies spare fibres of passage and offer fewer opportunities for compensatory changes because the effects are transient and short-lasting. Rats were infused prior to spatial working memory testing on a non-matching to place T-maze alternation task. Spatial working memory was impaired by dorsal but not ventral hippocampal inactivation. In a second experiment, infusion of the NMDAR antagonist, D-AP5, into dorsal hippocampus also impaired spatial working memory performance, suggesting that NMDAR function within the dorsal hippocampus makes an essential contribution to this aspect of hippocampal information processing.

Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisone, G.; Wu, C.F.; Consolo, S.

1987-10-01

A high density of galanin binding sites was found by using /sup 125/I-labeled galanin, iodinated by chloramine-T, followed by autoradiography in the ventral, but not in the dorsal, hippocampus of the rat. Lesions of the fimbria and of the septum caused disappearance of a major population of these binding sites, suggesting that a large proportion of them is localized on cholinergic nerve terminals of septal afferents. As a functional correlate to these putative galanin receptor sites, it was shown, both in vivo and in vitro, that galanin, in a concentration-dependent manner, inhibited the evoked release of acetylcholine in the ventral,more » but not in the dorsal, hippocampus. Intracerebroventricularly applied galanin fully inhibited the scopolamine stimulated release of acetylcholine in the ventral, but not in the dorsal, hippocampus, as measured by the microdialysis technique. In vitro, galanin inhibited the 25 mM K/sup +/-evoked release of (/sup 3/H)acetylcholine from slices of the ventral hippocampus, with an IC/sub 50/ value of approx. = 50 nM. These results are discussed with respect to the colocalization of galanin- and choline acetyltransferase-like immunoreactivity in septal somata projecting to the hippocampus.« less

Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri.

PubMed

Mathew, Jobin; Gangadharan, Gireesh; Kuruvilla, Korah P; Paulose, C S

2011-01-01

In the present study, alterations of the General GABA and GABA(A) receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B(max) (P < 0.001) compared to control. Real Time PCR amplification of GABA(A) receptor sub-units such as GABA(Aά₁), GABA(Aά₅) GABA(Aδ), and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA(Aγ) subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.

Historical and contemporary population genetic connectivity of the European short-snouted seahorse Hippocampus hippocampus and implications for management.

PubMed

Woodall, L C; Koldewey, H J; Shaw, P W

2011-06-01

This first genetic study of Hippocampus hippocampus covers the species' entire geographic range and employs two mtDNA markers (control region and cytochrome b) to establish patterns of population structuring. A total of 255 specimens from 21 locations were used to obtain 89 concatenated haplotypes. The common haplotype was present in all but one population, however, most haplotypes were unique. The haplotype network had a star-like construction, suggesting expansion from a bottleneck event. F(ST) and AMOVA revealed population subdivision into three geographic regions (English Channel + Bay of Biscay, Mediterranean Sea + Atlantic Ocean Iberian coast + Macaronesian Islands, and West Africa) with barriers to gene flow indentified at Cape Finisterre and the Cape Verde frontal zone. Neutrality tests and nested clade analysis suggest a complex demographic history, with both historic events and contemporary processes shaping patterns of genetic differentiation. The genetic population subdivision detected in this study indicates that H. hippocampus should be managed as three separate units. This is especially pertinent as H. hippocampus populations within the West African region are the only ones known to be specifically targeted for exploitation. © 2011 The Authors. Journal of Fish Biology © 2011 The Fisheries Society of the British Isles.

NEOCORTICAL ACTIVATION OF THE HIPPOCAMPUS DURING SLEEP IN INFANT RATS

PubMed Central

Mohns, Ethan J.; Blumberg, Mark S.

2010-01-01

We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5–6-day-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation upon which coordinated activity between these two forebrain structures develops. PMID:20203203

Treadmill exercise prevents diabetes-induced increases in lipid peroxidation and decreases in Cu,Zn-superoxide dismutase levels in the hippocampus of Zucker diabetic fatty rats.

PubMed

Kim, Jong Whi; Chae, Junghyun; Nam, Sung Min; Kim, Yo Na; Yoo, Dae Young; Choi, Jung Hoon; Jung, Hyo Young; Song, Wook; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

2015-01-01

In the present study, we investigated the effects of treadmill exercise on lipid peroxidation and Cu,Zn-superoxide dismutase (SOD1) levels in the hippocampus of Zucker diabetic fatty (ZDF) rats and lean control rats (ZLC) during the onset of diabetes. At 7 weeks of age, ZLC and ZDF rats were either placed on a stationary treadmill or made to run for 1 h/day for 5 consecutive days at 16~22 m/min for 5 weeks. At 12 weeks of age, the ZDF rats had significantly higher blood glucose levels and body weight than the ZLC rats. In addition, malondialdehyde (MDA) levels in the hippocampus of the ZDF rats were significantly higher than those of the ZLC rats whereas SOD1 levels in the hippocampus of the ZDF rats were moderately decreased. Notably, treadmill exercise prevented the increase of blood glucose levels in ZDF rats. In addition, treadmill exercise significantly ameliorated changes in MDA and SOD1 levels in the hippocampus although SOD activity was not altered. These findings suggest that diabetes increases lipid peroxidation and decreases SOD1 levels, and treadmill exercise can mitigate diabetes-induced oxidative damage in the hippocampus.

Synaptophysin and the dopaminergic system in hippocampus are involved in the protective effect of rutin against trimethyltin-induced learning and memory impairment.

PubMed

Zhang, Lei; Zhao, Qi; Chen, Chun-Hai; Qin, Qi-Zhong; Zhou, Zhou; Yu, Zheng-Ping

2014-09-01

This study aimed to investigate the protective effect of rutin against trimethyltin-induced spatial learning and memory impairment in mice. This study focused on the role of synaptophysin, growth-associated protein 43 and the action of the dopaminergic system in mechanisms associated with rutin protection and trimethyltin-induced spatial learning and memory impairment. Cognitive learning and memory was measured by Morris Water Maze. The expression of synaptophysin and growth-associated protein 43 in hippocampus was analyzed by western blot. The concentrations of dopamine, homovanillic acid, and dihyroxyphenylacetic acid in hippocampus were detected using reversed phase high-performance liquid chromatography with electrochemical detection. Trimethyltin-induced spatial learning impairment showed a dose-dependent mode. Synaptophysin but not growth-associated protein 43 was decreased in the hippocampus after trimethyltin administration. The concentration of dopamine decreased, while homovanillic acid increased in the hippocampus after trimethyltin administration. Mice pretreated with 20 mg/kg of rutin for 7 consecutive days exhibited improved water maze performance. Moreover, rutin pretreatment reversed the decrease of synaptophysin expression and dopamine alteration. These results suggest that rutin may protect against spatial memory impairment induced by trimethyltin. Synaptophysin and the dopaminergic system may be involved in trimethyltin-induced neuronal damage in hippocampus.

Effects of naringin on learning and memory dysfunction induced by gp120 in rats.

PubMed

Qin, Shanshan; Chen, Qiang; Wu, Hui; Liu, Chenglong; Hu, Jing; Zhang, Dalei; Xu, Changshui

2016-06-01

The aim of the present study was to investigate the effects of naringin on learning and memory dysfunction induced by HIV-1-enveloped protein gp120 in rats, and to identify its potential mechanisms of action. Learning and memory ability was evaluated via Morris water maze test, P2X7 receptor and P65 protein expressions in the rat hippocampus were detected by western blot analysis, and P2X7 mRNA expression in the hippocampus was measured by RT-PCR. We also recorded P2X7 agonist BzATP-activated current in the hippocampus via patch clamp technique. The results showed that naringin treatment (30mg/kg/day) markedly decreased the escape latency and target platform errors of rats treated with gp120 (50ng/day), and further, that naringin treatment significantly decreased the expression of P2X7 and P65 protein and P2X7 mRNA in the hippocampus of gp120-treated rats. In addition, naringin treatment reduced BzATP-activated current in the hippocampus of gp120-treated rats. These results altogether demonstrated that naringin can improve gp120-induced learning and memory dysfunction via mechanisms involving the inhibition of P2X7 expression in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.

Concentration- and age-dependent effects of chronic caffeine on contextual fear conditioning in C57BL/6J mice

PubMed Central

Poole, Rachel L.; Braak, David; Gould, Thomas J.

2015-01-01

Chronic caffeine exerts negligible effects on learning and memory in normal adults, but it is unknown whether this is also true for children and adolescents. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning in pre-adolescents and adolescents compared with adults. Here, we characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. The results indicate that chronic exposure to caffeine during pre-adolescence and adolescence enhances or impairs contextual conditioning depending on concentration, yet has no effect on cued conditioning. In contrast, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. No changes in learning were seen for adult mice for either the chronic caffeine or withdrawal conditions. These findings support the hypothesis that chronic exposure to caffeine during pre-adolescence and adolescence can alter learning and memory and as changes were only seen in hippocampus-dependent learning, this suggests that the developing hippocampus may be sensitive to the effects of caffeine. PMID:25827925

The cortical structure of consolidated memory: a hypothesis on the role of the cingulate-entorhinal cortical connection.

PubMed

Insel, Nathan; Takehara-Nishiuchi, Kaori

2013-11-01

Daily experiences are represented by networks of neurons distributed across the neocortex, bound together for rapid storage and later retrieval by the hippocampus. While the hippocampus is necessary for retrieving recent episode-based memory associations, over time, consolidation processes take place that enable many of these associations to be expressed independent of the hippocampus. It is generally thought that mechanisms of consolidation involve synaptic weight changes between cortical regions; or, in other words, the formation of "horizontal" cortico-cortical connections. Here, we review anatomical, behavioral, and physiological data which suggest that the connections in and between the entorhinal and cingulate cortices may be uniquely important for the long-term storage of memories that initially depend on the hippocampus. We propose that current theories of consolidation that divide memory into dual systems of hippocampus and neocortex might be improved by introducing a third, middle layer of entorhinal and cingulate allocortex, the synaptic weights within which are necessary and potentially sufficient for maintaining initially hippocampus-dependent associations over long time periods. This hypothesis makes a number of still untested predictions, and future experiments designed to address these will help to fill gaps in the current understanding of the cortical structure of consolidated memory. Copyright © 2013 Elsevier Inc. All rights reserved.

Kainic acid-mediated increase of preprotachykinin-A messenger RNA expression in the rat hippocampus and a region-selective attenuation by dexamethasone.

PubMed

Brené, S; Lindefors, N; Ballarin, M; Persson, H

1992-10-01

The hippocampus contains the highest number of glucocorticoid-sensitive neurons in the rat brain and excessive exposure to glucocorticoids can cause damage to hippocampal neurons and impair the capacity of the hippocampus to survive neuronal insults. In this study in situ hybridization combined with quantitative image analysis was used to study preprotachykinin-A mRNA levels after administration of a toxic dose of kainic acid in animals pretreated with glucocorticoids. Kainic acid was injected into dorsal hippocampus CA3 region in animals pretreated with the synthetic glucocorticoid receptor agonist dexamethasone and in control animals. Preprotachykinin-A mRNA was not detected in the hippocampus of untreated animals or in animals analysed 30 min after a kainic acid injection. However, 4 h after injection of kainic acid, the level of preprotachykinin-A mRNA increased to 20-times above the detection limit both in the dentate gyrus and the CA3 region of the hippocampus. Treatment of kainic acid-injected animals with dexamethasone 30 min before and 2 h after the injection attenuated the increase in the granule cells of the dentate gyrus by 50%. In contrast, dexamethasone pretreatment had no significant effect on the kainic acid-induced increase of preprotachykinin-A mRNA in pyramidal cells in regions CA3 or CA1. These results show that an excitatory stimulus within the hippocampus causes a substantial increase in the level of preprotachykinin-A mRNA in hippocampal granule and pyramidal cells and suggest that in granule cells of the dentate gyrus this increase can be modulated by glucocorticoids.

Neuronal connections, cell formation and cell migration in the perinatal human hippocampal dentate gyrus.

PubMed

Seress, L

1998-06-01

Jean Piaget's "stage theory" suggests that cognitive development proceeds in discrete steps, among which the first is the sensorimotor period that occupies the first two years. In recent years it became clear that an intact and mature hippocampus is necessary for memory formation both in experimental animals and in human. In the present experiments the perinatal morphological development of the human hippocampus was studied to describe structural changes that may correlate with the developmental changes of intellectual growth. Our results suggest that cell formation in the human hippocampus terminates several weeks before birth, but immature cells migrate to their final positions through the first six postnatal months. The newborn hippocampus contains all cell types and cell layers that are characteristic for the adult hippocampus. However, changes of the light microscopic features of the postsynaptic target neurons of hippocampal granule cells indicate that connections between granule cells and their target neurons are immature at birth and develop through an extended period of time that may last for three years. Since this neuronal connection is the first link in the chain of the main hippocampal synaptic circuitry, it may be suggested that human hippocampus is functionally impaired at birth. This period of light microscopic morphological maturation correlates well with the time period of Piaget's first stage of cognitive development. It can also be suggested that the prolonged postnatal development of some neuronal circuitries in the human hippocampus may be responsible for the psychological phenomenon of "infantile amnesia", that is the lack of memory traces from the early postnatal period.

Noopept stimulates the expression of NGF and BDNF in rat hippocampus.

PubMed

Ostrovskaya, R U; Gudasheva, T A; Zaplina, A P; Vahitova, Ju V; Salimgareeva, M H; Jamidanov, R S; Seredenin, S B

2008-09-01

We studied the effect of original dipeptide preparation Noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111) with nootropic and neuroprotective properties on the expression of mRNA for neurotropic factors NGF and BDNF in rat hippocampus. Expression of NGF and BDNF mRNA in the cerebral cortex and hippocampus was studied by Northern blot analysis. Taking into account the fact that pharmacological activity of Noopept is realized after both acute and chronic treatment, we studied the effect of single and long-term treatment (28 days) with this drug. Expression of the studied neurotropic factors in the cerebral cortex was below the control after single administration of Noopept, while chronic administration caused a slight increase in BDNF expression. In the hippocampus, expression of mRNA for both neurotrophins increased after acute administration of Noopept. Chronic treatment with Noopept was not followed by the development of tolerance, but even potentiated the neurotrophic effect. These changes probably play a role in neuronal restoration. We showed that the nootropic drug increases expression of neurotrophic factors in the hippocampus. Our results are consistent with the hypothesis that neurotrophin synthesis in the hippocampus determines cognitive function, particularly in consolidation and delayed memory retrieval. Published data show that neurotrophic factor deficiency in the hippocampus is observed not only in advanced Alzheimer's disease, but also at the stage of mild cognitive impairment (pre-disease state). In light of this our findings suggest that Noopept holds much promise to prevent the development of Alzheimer's disease in patients with mild cognitive impairment. Moreover, therapeutic effectiveness of Noopept should be evaluated at the initial stage of Alzheimer's disease.

Left hippocampus sparing whole brain radiotherapy (WBRT): A planning study.

PubMed

Kazda, Tomas; Vrzal, Miroslav; Prochazka, Tomas; Dvoracek, Petr; Burkon, Petr; Pospisil, Petr; Dziacky, Adam; Nikl, Tomas; Jancalek, Radim; Slampa, Pavel; Lakomy, Radek

2017-12-01

Unilateral sparing of the dominant (left) hippocampus during whole brain radiotherapy (WBRT) could mitigate cognitive decline, especially verbal memory, similar to the widely investigated bilateral hippocampus avoidance (HA-WBRT). The aim of this planning study is dosimetrical comparison of HA-WBRT with only left hippocampus sparing (LHA-WBRT) plans. HA-WBRT plans for 10 patients were prepared in accordance with RTOG 0933 trial and served as baseline for comparisons with several LHA-WBRT plans prepared with an effort: 1) to maintain the same left hippocampus dosimetry ("BEST PTV") and 2) to maintain same dosimetry in planning target volume as in HA-WBRT ("BEST LH"). All HA-WBRT plans met RTOG 0933 protocol criteria with a mean Conformity index 1.09 and mean Homogeneity index (HI) 0.21. Mean right and left hippocampal D100% was 7.8 Gy and 8.5 Gy and mean Dmax 14.0 Gy and 13.8 Gy, respectively. "BEST PTV" plans reduced HI by 31.2% (P=0.005) which is mirrored by lower PTV_D2% (-0.8 Gy, P=0.005) and higher PTV_D98% (+1.3 Gy, P=0.005) as well as decreased optic pathway's Dmax by 1 Gy. In "BEST LH", mean D100% and Dmax for the left hippocampus were significantly reduced by 11.2% (P=0.005) and 10.9% (P=0.005) respectively. LHA-WBRT could improve target coverage and/or further decrease in dose to spared hippocampus. Future clinical trials must confirm whether statistically significant reduction in left hippocampal dose is also clinically significant.

Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

PubMed

Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

2017-09-29

Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Neuroprotective effects of Bacopa monniera whole-plant extract against aluminum-induced hippocampus damage in rats: evidence from electron microscopic images.

PubMed

Nannepaga, John Sushma; Korivi, Mallikarjuna; Tirumanyam, Madhavi; Bommavaram, Mahitha; Kuo, Chia-Hua

2014-10-31

Impaired antioxidant system and structural changes in hippocampus are considered as key instigators of neurodegenerative diseases. The present study aimed to investigate the antioxidant and tissue protective properties of Bacopa monniera whole-plant extract (BME) against aluminum (Al)- induced oxidative stress and hippocampus damage in rats. Male Wistar rats were evenly divided into four groups, nine in each and labeled as control, Al treated (10 mg/kg), BME administered (40 mg/kg) and combination of both Al plus BME (Al+BME) treated groups. After one month of treatment by oral administration, antioxidant status was determined, and structural changes in the hippocampus were evaluated by electron microscopy. Al-induced increased oxidative damage in the hippocampus was revealed by elevated thiobarbituric acid reactive substances (TBARS). This increased lipid peroxidation was associated with significantly decreased antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). However, aluminum intoxicated rats treated with BME for 30 days showed significantly restored antioxidant enzyme activities along with decreased TBARS (P < 0.01). Further evidences from electron micrographs clearly indicated that Al-induced vacuolation, lipofuscin deposition and pyramidal cell degeneration in the hippocampus was attenuated with co-administration of the whole-plant extract. Our results demonstrate that structural derangement in hippocampus by aluminum is directly proportionate with increased lipid peroxidation. Nevertheless, B. monniera treatment potentiates the antioxidant status and suppressed the tissue damage induced by Al-intoxication. These findings suggest that B. monniera whole-plant extracts can be considered as a possible remedy to counteract aluminum-associated neurological disorders.

The role of the human hippocampus in familiarity-based and recollection-based recognition memory

PubMed Central

Wixted, John T.; Squire, Larry R.

2010-01-01

The ability to recognize a previously encountered stimulus is dependent on the structures of the medial temporal lobe and is thought to be supported by two processes, recollection and familiarity. A focus of research in recent years concerns the extent to which these two processes depend on the hippocampus and on the other structures of the medial temporal lobe. One view holds that the hippocampus is important for both processes, whereas a different view holds that the hippocampus supports only the recollection process and the perirhinal cortex supports the familiarity process. One approach has been to study patients with hippocampal lesions and to contrast old/new recognition (which can be supported by familiarity) to free recall (which is supported by recollection). Despite some early case studies suggesting otherwise, several group studies have now shown that hippocampal patients exhibit comparable impairments on old/new recognition and free recall. These findings suggest that the hippocampus is important for both recollection and familiarity. Neuroimaging studies and Receiver Operating Characteristic analyses also initially suggested that the hippocampus was specialized for recollection, but these studies involved a strength confound (strong memories have been compared to weak memories). When steps are taken to compare strong recollection-based memories with strong familiarity-based memories, or otherwise control for memory strength, evidence for a familiarity signal (as well as a recollection signal) is evident in the hippocampus. These findings suggest that the functional organization of the medial temporal lobe is probably best understood in terms unrelated to the distinction between recollection and familiarity. PMID:20412819

Differential Age-Related Changes in Structural Covariance Networks of Human Anterior and Posterior Hippocampus.

PubMed

Li, Xinwei; Li, Qiongling; Wang, Xuetong; Li, Deyu; Li, Shuyu

2018-01-01

The hippocampus plays an important role in memory function relying on information interaction between distributed brain areas. The hippocampus can be divided into the anterior and posterior sections with different structure and function along its long axis. The aim of this study is to investigate the effects of normal aging on the structural covariance of the anterior hippocampus (aHPC) and the posterior hippocampus (pHPC). In this study, 240 healthy subjects aged 18-89 years were selected and subdivided into young (18-23 years), middle-aged (30-58 years), and older (61-89 years) groups. The aHPC and pHPC was divided based on the location of uncal apex in the MNI space. Then, the structural covariance networks were constructed by examining their covariance in gray matter volumes with other brain regions. Finally, the influence of age on the structural covariance of these hippocampal sections was explored. We found that the aHPC and pHPC had different structural covariance patterns, but both of them were associated with the medial temporal lobe and insula. Moreover, both increased and decreased covariances were found with the aHPC but only increased covariance was found with the pHPC with age ( p < 0.05, family-wise error corrected). These decreased connections occurred within the default mode network, while the increased connectivity mainly occurred in other memory systems that differ from the hippocampus. This study reveals different age-related influence on the structural networks of the aHPC and pHPC, providing an essential insight into the mechanisms of the hippocampus in normal aging.

Detecting representations of recent and remote autobiographical memories in vmPFC and hippocampus

PubMed Central

Bonnici, Heidi M.; Chadwick, Martin J.; Lutti, Antoine; Hassabis, Demis; Weiskopf, Nikolaus; Maguire, Eleanor A.

2012-01-01

How autobiographical memories are represented in the human brain and whether this changes with time are questions central to memory neuroscience. Two regions in particular have been consistently implicated, the ventromedial prefrontal cortex (vmPFC) and the hippocampus, although their precise contributions are still contested. The key question in this debate, when reduced to its simplest form, concerns where information about specific autobiographical memories is located. Here we availed ourselves of the opportunity afforded by multi-voxel pattern analysis (MVPA) to provide an alternative to conventional neuropsychological and fMRI approaches, by detecting representations of individual autobiographical memories in patterns of fMRI activity. We examined whether information about specific recent (two weeks old) and remote (ten years old) autobiographical memories was represented in vmPFC and hippocampus, and other medial temporal and neocortical regions. vmPFC contained information about recent and remote autobiographical memories, although remote memories were more readily detected there, indicating that consolidation or a change of some kind had occurred. Information about both types of memory was also present in the hippocampus, suggesting it plays a role in the retrieval of vivid autobiographical memories regardless of remoteness. Interestingly, we also found that while recent and remote memories were both represented within anterior and posterior hippocampus, the latter nevertheless contained more information about remote memories. Thus, like vmPFC, the hippocampus too respected the distinction between recent and remote memories. Overall, these findings clarify and extend our view of vmPFC and hippocampus while also informing systems-level consolidation and providing clear targets for future studies. PMID:23175849

Neuroprotective role of curcumin on the hippocampus against the structural and serological alterations of streptozotocin-induced diabetes in Sprague Dawely rats.

PubMed

Faheem, Nermeen Mohammed; El Askary, Ahmad

2017-06-01

Diabetes mellitus causes impaired memory and cognitive functions. The hippocampus plays a key role in memory and learning. Curcumin attenuates diabetic nephropathy in vivo . Curcumin has shown a neurogenic effect and cognition-enhancing potential in aged rats. The aim of this study is to evaluate the possible protective role of curcumin on the histological and serological changes of the hippocampus in diabetic rats. Forty albino rats were divided into four groups, ten rats each. Group 1 control rats, group 2 rats received curcumin orally (200 mg/kg/day for six weeks), group 3 rats were injected intraperitoneally with streptozotocin (STZ) (100 mg/kg, single dose), group 4 received a single injection of STZ and received curcumin orally for six weeks. Paraffin sections of hippocampus were prepared and stained with hematoxylin and eosin stain, and immnunohistochemical staining for GFAP and caspase-3. Morphometrical and statistical analyses were performed. Glycemic status and parameters of oxidative stress was measured. Examination of hippocampus of diabetic rats showed disorganization of small pyramidal cells in CA1, many cellular losses in the pyramidal cells of CA3, many degenerated granule cells in the dentate gyrus. GFAP positive astrocyte and caspase-3 positive neuron counts were significantly increased. There were significant serum glucose elevation and significant lowered levels of oxidative stress parameters as compared to control rats. Curcumin administration improved the structural and serological alterations of the hippocampus with significant reduction in serum glucose level. Curcumin ameliorates the deterious effect of diabetes on the hippocampus through its antioxidant, antiapoptotic and anti-inflammatory efficacies.

Retrieval-Induced Upregulation of Tet3 in Pyramidal Neurons of the Dorsal Hippocampus Mediates Cocaine-Associated Memory Reconsolidation

PubMed Central

Liu, Cao; Sun, Xue; Wang, Zhilin; Le, Qiumin; Liu, Peipei; Jiang, Changyou; Wang, Feifei; Ma, Lan

2018-01-01

Abstract Background Memory retrieval refers to reexposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. Methods We used cocaine-induced conditioned place preference to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dorsal hippocampus. We isolated the ribosome-associated transcripts from the excitatory neurons in the dorsal hippocampus by RiboTag purification to identify the potential epigenetic regulators, and we specifically knocked down gene expression in pyramidal neurons with a Cre-dependent lentivirus. Results Chemogenetically silencing the activity of the pyramidal neurons in the dorsal hippocampus immediately after memory retrieval markedly impaired memory reconsolidation, and the ribosome-associated mRNA level of the ten-eleven translocation (Tet) family methylcytosine dioxygenase Tet3, but not Tet1 or Tet2, was dramatically upregulated 10 minutes after memory retrieval. The protein level of Tet3 in the dorsal hippocampus but not in the anterior cingulate cortex was dramatically increased 1 hour after memory retrieval. Specifically, knockdown of Tet3 in pyramidal neurons in the dorsal hippocampus decreased the activation of pyramidal neurons and impaired the reconsolidation of cocaine-associated memory. Conclusions Our findings highlight the new function of the DNA demethylation regulator Tet3 in pyramidal neurons of the dorsal hippocampus in regulating the reconsolidation of cocaine-associated memory. PMID:29106571

The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases.

PubMed

Slade, Alexander N; Stanic, Sinisa

2016-03-01

Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for <10% of their patients. The most common reason for not using Memantine was a poor patient performance status, and limited life expectancy. Likewise, 56% of radiation oncologists would not change their clinical practice to include hippocampus sparing IMRT in patients receiving WBRT based on the results of RTOG 0933. Further validation of hippocampus sparing in a phase III trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

PubMed Central

Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen

2013-01-01

Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions. PMID:23418609

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory

PubMed Central

Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

2005-01-01

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory. PMID:16011544

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

PubMed

Moscovitch, Morris; Rosenbaum, R Shayna; Gilboa, Asaf; Addis, Donna Rose; Westmacott, Robyn; Grady, Cheryl; McAndrews, Mary Pat; Levine, Brian; Black, Sandra; Winocur, Gordon; Nadel, Lynn

2005-07-01

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

Maternal Exposure to Ethanol During Pregnancy and Lactation Affects Glutamatergic System and Induces Oxidative Stress in Offspring Hippocampus.

PubMed

Cesconetto, Patricia A; Andrade, Camila M; Cattani, Daiane; Domingues, Juliana T; Parisotto, Eduardo B; Filho, Danilo W; Zamoner, Ariane

2016-01-01

Alcohol abuse during pregnancy leads to intellectual disability and morphological defects in the offspring. The aim of this study was to determine the effect of chronic maternal ethanol (EtOH) consumption during pregnancy and lactation on glutamatergic transmission regulation, energy deficit, and oxidative stress in the hippocampus of the offspring. EtOH was administered to dams in drinking water at increasing doses (2 to 20%) from the gestation day 5 to lactation day 21. EtOH and tap water intake by treated and control groups, respectively, were measured daily. Results showed that EtOH exposure does not affect fluid intake over the course of pregnancy and lactation. The toxicity of maternal exposure to EtOH was demonstrated by decreased offspring body weight at experimental age, on postnatal day 21. Moreover, maternal EtOH exposure decreased (45) Ca(2+) influx in the offspring's hippocampus. Corroborating this finding, EtOH increased both Na(+) -dependent and Na(+) -independent glial [(14) C]-glutamate uptake in hippocampus of immature rats. Also, maternal EtOH exposure decreased glutamine synthetase activity and induced aspartate aminotransferase enzymatic activity, suggesting that in EtOH-exposed offspring hippocampus, glutamate is preferentially used as a fuel in tricarboxylic acid cycle instead of being converted into glutamine. In addition, EtOH exposure decreased [U-14C]-2-deoxy-D-glucose uptake in offspring hippocampus. The decline in glucose transport coincided with increased lactate dehydrogenase activity, suggesting an adaptative response in EtOH-exposed offspring hippocampus, using lactate as an alternative fuel. These events were associated with oxidative damage, as demonstrated by changes in the enzymatic antioxidant defense system and lipid peroxidation. Taken together, the results demonstrate that maternal exposure to EtOH during pregnancy and lactation impairs glutamatergic transmission, as well as inducing oxidative stress and energy deficit in immature rat hippocampus. Copyright © 2016 by the Research Society on Alcoholism.

Methamphetamine differentially affects BDNF and cell death factors in anatomically defined regions of the hippocampus

PubMed Central

Galinato, Melissa H.; Orio, Laura; Mandyam, Chitra D.

2014-01-01

Methamphetamine exposure reduces hippocampal long-term potentiation (LTP) and neurogenesis and these alterations partially contribute to hippocampal maladaptive plasticity. The potential mechanisms underlying methamphetamine-induced maladaptive plasticity were identified in the present study. Expression of brain-derived neurotrophic factor (BDNF; a regulator of LTP and neurogenesis), and its receptor tropomyosin-related kinase B (TrkB) were studied in the dorsal and ventral hippocampal tissue lysates in rats that intravenously self-administered methamphetamine in a limited access (1 h/day) or extended access (6 h/day) paradigm for 17 days post baseline sessions. Extended access methamphetamine enhanced expression of BDNF with significant effects observed in the dorsal and ventral hippocampus. Methamphetamine-induced enhancements in BDNF expression were not associated with TrkB receptor activation as indicated by phospho (p)-TrkB-706 levels. Conversely, methamphetamine produced hypophosphorylation of NMDA receptor subunit 2B (GluN2B) at Tyr-1472 in the ventral hippocampus, indicating reduced receptor activation. In addition, methamphetamine enhanced expression of anti-apoptotic protein Bcl-2 and reduced pro-apoptotic protein Bax levels in the ventral hippocampus, suggesting a mechanism for reducing cell death. Analysis of Akt, a pro-survival kinase that suppresses apoptotic pathways and pAkt at Ser-473 demonstrated that extended access methamphetamine reduces Akt expression in the ventral hippocampus. These data reveal that alterations in Bcl-2 and Bax levels by methamphetamine were not associated with enhanced Akt expression. Given that hippocampal function and neurogenesis vary in a subregion-specific fashion, where dorsal hippocampus regulates spatial processing and has higher levels of neurogenesis, whereas ventral hippocampus regulates anxiety-related behaviors, these data suggest that methamphetamine self-administration initiates distinct allostatic changes in hippocampal subregions that may contribute to the altered synaptic activity in the hippocampus, which may underlie enhanced negative affective symptoms and perpetuation of the addiction cycle. PMID:25463524

Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation

PubMed Central

Lee, Michael L.; Katsuyama, Ângela M.; Duge, Leanne S.; Sriram, Chaitra; Krushelnytskyy, Mykhaylo; Kim, Jeansok J.; de la Iglesia, Horacio O.

2016-01-01

Study Objectives: Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation. Methods: We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations post-training will impair memory consolidation irrespective of total sleep duration. Results: When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the post-training fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory. Conclusions: Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation. Citation: Lee ML, Katsuyama AM, Duge LS, Sriram C, Krushelnytskyy M, Kim JJ, de la Iglesia HO. Fragmentation of rapid eye movement and nonrapid eye movement sleep without total sleep loss impairs hippocampus-dependent fear memory consolidation. SLEEP 2016;39(11):2021–2031. PMID:27568801

Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prokic, Vesna, E-mail: vesna.prokic@uniklinik-freiburg.de; Wiedenmann, Nicole; Fels, Franziska

2013-01-01

Purpose: To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Methods and Materials: Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individualmore » brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. Results: The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55 {+-} 0.62 Gy and 6.29 {+-} 0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8 {+-} 1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2 {+-} 0.7 Gy and 32.7 {+-} 0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23 {+-} 1.42 Gy in SC. Conclusions: Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.« less

Examining the Role of the Human Hippocampus in Approach-Avoidance Decision Making Using a Novel Conflict Paradigm and Multivariate Functional Magnetic Resonance Imaging.

PubMed

O'Neil, Edward B; Newsome, Rachel N; Li, Iris H N; Thavabalasingam, Sathesan; Ito, Rutsuko; Lee, Andy C H

2015-11-11

Rodent models of anxiety have implicated the ventral hippocampus in approach-avoidance conflict processing. Few studies have, however, examined whether the human hippocampus plays a similar role. We developed a novel decision-making paradigm to examine neural activity when participants made approach/avoidance decisions under conditions of high or absent approach-avoidance conflict. Critically, our task required participants to learn the associated reward/punishment values of previously neutral stimuli and controlled for mnemonic and spatial processing demands, both important issues given approach-avoidance behavior in humans is less tied to predation and foraging compared to rodents. Participants played a points-based game where they first attempted to maximize their score by determining which of a series of previously neutral image pairs should be approached or avoided. During functional magnetic resonance imaging, participants were then presented with novel pairings of these images. These pairings consisted of images of congruent or opposing learned valences, the latter creating conditions of high approach-avoidance conflict. A data-driven partial least squares multivariate analysis revealed two reliable patterns of activity, each revealing differential activity in the anterior hippocampus, the homolog of the rodent ventral hippocampus. The first was associated with greater hippocampal involvement during trials with high as opposed to no approach-avoidance conflict, regardless of approach or avoidance behavior. The second pattern encompassed greater hippocampal activity in a more anterior aspect during approach compared to avoid responses, for conflict and no-conflict conditions. Multivoxel pattern classification analyses yielded converging findings, underlining a role of the anterior hippocampus in approach-avoidance conflict decision making. Approach-avoidance conflict has been linked to anxiety and occurs when a stimulus or situation is associated with reward and punishment. Although rodent work has implicated the hippocampus in approach-avoidance conflict processing, there is limited data on whether this role applies to learned, as opposed to innate, incentive values, and whether the human hippocampus plays a similar role. Using functional neuroimaging with a novel decision-making task that controlled for perceptual and mnemonic processing, we found that the human hippocampus was significantly active when approach-avoidance conflict was present for stimuli with learned incentive values. These findings demonstrate a role for the human hippocampus in approach-avoidance decision making that cannot be explained easily by hippocampal-dependent long-term memory or spatial cognition. Copyright © 2015 the authors 0270-6474/15/3515040-11$15.00/0.

Abstract memory representations in the ventromedial prefrontal cortex and hippocampus support concept generalization.

PubMed

Bowman, Caitlin R; Zeithamova, Dagmar

2018-02-07

Memory function involves both the ability to remember details of individual experiences and the ability to link information across events to create new knowledge. Prior research has identified the ventromedial prefrontal cortex (VMPFC) and the hippocampus as important for integrating across events in service of generalization in episodic memory. The degree to which these memory integration mechanisms contribute to other forms of generalization, such as concept learning, is unclear. The present study used a concept-learning task in humans (both sexes) coupled with model-based fMRI to test whether VMPFC and hippocampus contribute to concept generalization, and whether they do so by maintaining specific category exemplars or abstract category representations. Two formal categorization models were fit to individual subject data: a prototype model that posits abstract category representations and an exemplar model that posits category representations based on individual category members. Latent variables from each of these models were entered into neuroimaging analyses to determine whether VMPFC and the hippocampus track prototype or exemplar information during concept generalization. Behavioral model fits indicated that almost three quarters of the subjects relied on prototype information when making judgments about new category members. Paralleling prototype dominance in behavior, correlates of the prototype model were identified in VMPFC and the anterior hippocampus with no significant exemplar correlates. These results indicate that the VMPFC and portions of the hippocampus play a broad role in memory generalization and that they do so by representing abstract information integrated from multiple events. SIGNIFICANCE STATEMENT Whether people represent concepts as a set of individual category members or by deriving generalized concept representations abstracted across exemplars has been debated. In episodic memory, generalized memory representations have been shown to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC-hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus. Copyright © 2018 the authors.

Regional convection-enhanced delivery of gadolinium-labeled albumin in the rat hippocampus in vivo.

PubMed

Astary, Garrett W; Kantorovich, Svetlana; Carney, Paul R; Mareci, Thomas H; Sarntinoranont, Malisa

2010-03-15

Convection-enhanced delivery (CED) has emerged as a promising method of targeted drug delivery for treating central nervous system (CNS) disorders, but the influence of brain structure on infusate distribution is unclear. We have utilized this approach to study extracellular transport and distribution of a contrast agent in the hippocampus, a complex structure susceptible to CNS disorders. The magnetic resonance (MR) contrast agent diethylene triamene penta-acetic acid chelated gadolinium-labeled albumin (Gd-albumin), tagged with Evans blue dye, was directly infused (V(i)=5 microl) into the dorsal and ventral hippocampus of seven male Sprague-Dawley rats. The final distribution profile of the contrast agent, a product of CED and limited diffusion, was observed in vivo using high-resolution T1-weighted MR imaging at 11.1T. Dense cell layers, such as the granule cell layer of the dentate gyrus and the pyramidal cell layer of CA1, appeared to be barriers to transport of the tracer. Three-dimensional distribution shape and volume (V(d)) differences, between the dorsal and ventral hippocampus infusions, were determined from the MR images using a semi-automatic segmentation routine (dorsal V(d)=23.4+/-1.8 microl, ventral V(d)=36.4+/-5.1 microl). Finer structural detail of the hippocampus was obtained using a combination of histological analysis and fluorescence imaging. This study demonstrates that CED has the potential to target all regions of the hippocampus and that tracer distribution is influenced by infusion site, underlying structure and circuitry, and extent of backflow. Therefore, CED, combined with high-resolution MR imaging, may be a useful strategy for delivering therapeutics for the treatment of CNS disorders affecting the hippocampus. Published by Elsevier B.V.

Role of the parahippocampal cortex in memory for the configuration but not the identity of objects: converging evidence from patients with selective thermal lesions and fMRI.

PubMed

Bohbot, Véronique D; Allen, John J B; Dagher, Alain; Dumoulin, Serge O; Evans, Alan C; Petrides, Michael; Kalina, Miroslav; Stepankova, Katerina; Nadel, Lynn

2015-01-01

The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus.

Release of endogenous amino acids from the hippocampus and brain stem from developing and adult mice in ischemia.

PubMed

Oja, Simo S; Saransaari, Pirjo

2009-09-01

The release of neurotransmitters and modulators has been studied mostly using labeled preloaded compounds. For several reasons, however, the estimated release may not reliably reflect the release of endogenous compounds. The basal and K(+)-evoked release of the neuroactive endogenous amino acids GABA, glycine, taurine, L-glutamate and L-aspartate was now studied in slices from the hippocampus and brain stem from 7-day-old and 3-month-old mice under control and ischemic conditions. The release of synaptically not active L-glutamine, L-alanine, L-threonine and L-serine was assessed for comparison. The estimates for the hippocampus and brainstem were markedly different and also different in developing and adult mice. GABA release was much greater in 3-month-old than in 7-day-old mice, whereas with taurine the situation was the opposite, in the hippocampus in particular. K(+) stimulation enhanced glycine release more in the mature than immature brain stem while in the hippocampus the converse was observed. Ischemia enhanced the release of all neuroactive amino acids in both brain regions, the effects being relatively most pronounced in the case of GABA, aspartate and glutamate in the hippocampus in 3-month-old mice, and taurine in 7-day-old and glycine in 3-month-old mice in the brain stem. These results are qualitatively similar to those obtained on earlier experiments with labeled preloaded amino acids. However, the magnitudes of the release cannot be quite correctly estimated using radioactive labels. In developing mice only taurine release may counteract the harmful effects of excitatory amino acids in ischemia in both hippocampus and brain stem.

Neonatal handling enduringly decreases anxiety and stress responses and reduces hippocampus and amygdala volume in a genetic model of differential anxiety: Behavioral-volumetric associations in the Roman rat strains.

PubMed

Río-Álamos, Cristóbal; Oliveras, Ignasi; Piludu, Maria Antonietta; Gerbolés, Cristina; Cañete, Toni; Blázquez, Gloria; Lope-Piedrafita, Silvia; Martínez-Membrives, Esther; Torrubia, Rafael; Tobeña, Adolf; Fernández-Teruel, Alberto

2017-02-01

The hippocampus and amygdala have been proposed as key neural structures related to anxiety. A more active hippocampus/amygdala system has been related to greater anxious responses in situations involving conflict/novelty. The Roman Low- (RLA) and High-avoidance (RHA) rat lines/strains constitute a genetic model of differential anxiety. Relative to RHA rats, RLA rats exhibit enhanced anxiety/fearfulness, augmented hippocampal/amygdala c-Fos expression following exposure to novelty/conflict, increased hippocampal neuronal density and higher endocrine responses to stress. Neonatal handling (NH) is an environmental treatment with long-lasting anxiety/stress-reducing effects in rodents. Since hippocampus and amygdala volume are supposed to be related to anxiety/fear, we hypothesized a greater volume of both areas in RLA than in RHA rats, as well as that NH treatment would reduce anxiety and the volume of both structures, in particular in the RLA strain. Adult untreated and NH-treated RHA and RLA rats were tested for anxiety, sensorimotor gating (PPI), stress-induced corticosterone and prolactin responses, two-way active avoidance acquisition and in vivo 7 T 1H-Magnetic resonance image. As expected, untreated RLA rats showed higher anxiety and post-stress hormone responses, as well as greater hippocampus and amygdala volumes than untreated RHA rats. NH decreased anxiety/stress responses, especially in RLA rats, and significantly reduced hippocampus and amygdala volumes in this strain. Dorsal striatum volume was not different between the strains nor it was affected by NH. Finally, there were positive associations (as shown by correlations, factor analysis and multiple regression) between anxiety and PPI and hippocampus/amygdala volumes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Multiple Scales of Representation along the Hippocampal Anteroposterior Axis in Humans.

PubMed

Brunec, Iva K; Bellana, Buddhika; Ozubko, Jason D; Man, Vincent; Robin, Jessica; Liu, Zhong-Xu; Grady, Cheryl; Rosenbaum, R Shayna; Winocur, Gordon; Barense, Morgan D; Moscovitch, Morris

2018-06-13

The ability to represent the world accurately relies on simultaneous coarse and fine-grained neural information coding, capturing both gist and detail of an experience. The longitudinal axis of the hippocampus may provide a gradient of representational granularity in spatial and episodic memory in rodents and humans [1-8]. Rodent place cells in the ventral hippocampus exhibit significantly larger place fields and greater autocorrelation than those in the dorsal hippocampus [1, 9-11], which may underlie a coarser and slower changing representation of space [10, 12]. Recent evidence suggests that properties of cellular dynamics in rodents can be captured with fMRI in humans during spatial navigation [13] and conceptual learning [14]. Similarly, mechanisms supporting granularity along the long axis may also be extrapolated to the scale of fMRI signal. Here, we provide the first evidence for separable scales of representation along the human hippocampal anteroposterior axis during navigation and rest by showing (1) greater similarity among voxel time courses and (2) higher temporal autocorrelation in anterior hippocampus (aHPC), relative to posterior hippocampus (pHPC), the human homologs of ventral and dorsal rodent hippocampus. aHPC voxels exhibited more similar activity at each time point and slower signal change over time than voxels in pHPC, consistent with place field organization in rodents. Importantly, similarity between voxels was related to navigational strategy and episodic memory. These findings provide evidence that the human hippocampus supports an anterior-to-posterior gradient of coarse-to-fine spatiotemporal representations, suggesting the existence of a cross-species mechanism, whereby lower neural similarity supports more complex coding of experience. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation.

PubMed

Lee, Michael L; Katsuyama, Ângela M; Duge, Leanne S; Sriram, Chaitra; Krushelnytskyy, Mykhaylo; Kim, Jeansok J; de la Iglesia, Horacio O

2016-11-01

Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation. We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations post-training will impair memory consolidation irrespective of total sleep duration. When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the post-training fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory. Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation. © 2016 Associated Professional Sleep Societies, LLC.

Functional network changes in the hippocampus contribute to depressive symptoms in epilepsy.

PubMed

Peng, Weifeng; Mao, Lingyan; Yin, Dazhi; Sun, Wei; Wang, He; Zhang, Qianqian; Wang, Jing; Chen, Caizhong; Zeng, Mengsu; Ding, Jing; Wang, Xin

2018-06-01

Our study aimed to investigate the functional connectivity (FC) between the hippocampus and other brain regions in epilepsy patients with depressive symptoms. Epilepsy patients with and without depressive symptoms, assessed using the 17-item Hamilton Depression Rating Scale scores, were enrolled. Healthy volunteers were recruited as the control group. Resting state functional magnetic resonance imaging was performed, and the data were processed using Resting-State fMRI (DPARSFA2.0) software. The regional homogeneity (ReHo) values and the FC between the right hippocampus and other brain regions were analysed. The ReHo value of the cerebellum (particularly the left cerebellar hemisphere) was significantly lower in epilepsy patients than in healthy controls, and was lower in epilepsy patients with depressive symptoms (EP + DS group) than in those without depressive symptoms (EP-DS group, p < 0.05). Additionally, the FC between the right hippocampus and the bilateral cerebellum was significantly greater in the EP + DS group than in the EP-DS group (p < 0.05). Moreover, abnormal ReHo values in the bilateral frontal lobes, including the right anterior cingulate cortex, and changes in the FC between the right hippocampus and the bilateral frontal lobes were found in the EP + DS group. Minor changes in the FC between the temporal and parietal lobes were also found in the epilepsy patients. The functional right hippocampus-cerebellum circuit might contribute to the pathogenesis of depressive symptoms in epilepsy, with the exception of brain areas associated with emotion such as the frontal and temporal lobes. Modulating the hippocampus-cerebellum circuit is a potential therapeutic strategy for epilepsy patients with depressive symptoms. Copyright © 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Involvement of the lateral septum and the ventral Hippocampus in the emotional sequelae induced by social defeat: role of glucocorticoid receptors.

PubMed

Calfa, Gastón; Bussolino, Daniela; Molina, Victor A

2007-07-19

An important area of the brain aversive circuitry is the lateral septum (LS), together with its principal connections to diverse Hippocampal regions. The aim of this work was to evaluate whether the LS-Hippocampus network participates in the increased anxiety-like behavior produced by a previous defeat experience. The neural activation of different regions of the Hippocampus was assessed by the number of Fos positive cells in animals previously defeated. A notable elevation in the expression of this protein was observed in CA1, CA2, CA3, and Dentate Gyrus, for both dorsal and ventral Hippocampus. The local administration of a glucocorticoid receptor (GR or type II) antagonist, but not of a mineralcorticoid receptor (MR or type II) antagonist, into the LS before the stressful stimuli prevented a rise in the number of Fos positive cells, especially in the ventral portion of the Hippocampus. Furthermore, to evaluate the role of these hippocampal portions in the modulation of the emotional sequelae induced by defeat, the dorsal or the ventral Hippocampus were inactivated by lidocaine at different times following the social confrontation, with the anxiety-like behavior being assessed in the elevated plus maze the next day. Only the inactivation of the ventral region attenuated the excessive anxiety exhibited by defeated animals. The infusion of lidocaine, 1h after the confrontation, did not affect this behavioral response. These data suggest a preferential participation of the LS and its connections to the ventral Hippocampus in the emotional sequelae induced by the social defeat. Moreover, the GR localized within the LS played an essential role in the modulation of this emotional state.

Hippocampal, amygdala, and neocortical synchronization of theta rhythms is related to an immediate recall during rey auditory verbal learning test.

PubMed

Babiloni, Claudio; Vecchio, Fabrizio; Mirabella, Giovanni; Buttiglione, Maura; Sebastiano, Fabio; Picardi, Angelo; Di Gennaro, Giancarlo; Quarato, Pier P; Grammaldo, Liliana G; Buffo, Paola; Esposito, Vincenzo; Manfredi, Mario; Cantore, Giampaolo; Eusebi, Fabrizio

2009-07-01

It is well known that theta rhythms (3-8 Hz) are the fingerprint of hippocampus, and that neural activity accompanying encoding of words differs according to whether the items are later remembered or forgotten ["subsequent memory effect" (SME)]. Here, we tested the hypothesis that temporal synchronization of theta rhythms among hippocampus, amygdala, and neocortex is related to immediate memorization of repeated words. To address this issue, intracerebral electroencephalographic (EEG) activity was recorded in five subjects with drug-resistant temporal lobe epilepsy (TLE), under presurgical monitoring routine. During the recording of the intracerebral EEG activity, the subjects performed a computerized version of Rey auditory verbal learning test (RAVLT), a popular test for the clinical evaluation of the immediate and delayed memory. They heard the same list of 15 common words for five times. Each time, immediately after listening the list, the subjects were required to repeat as many words as they could recall. Spectral coherence of the intracerebral EEG activity was computed in order to assess the temporal synchronization of the theta (about 3-8 Hz) rhythms among hippocampus, amygdala, and temporal-occipital neocortex. We found that theta coherence values between amygdala and hippocampus, and between hippocampus and occipital-temporal cortex, were higher in amplitude during successful than unsuccessful immediate recall. A control analysis showed that this was true also for a gamma band (40-45 Hz). Furthermore, these theta and gamma effects were not observed in an additional (control) subject with drug-resistant TLE and a wide lesion to hippocampus. In conclusion, a successful immediate recall to the RAVLT was associated to the enhancement of temporal synchronization of the theta (gamma) rhythms within a cerebral network including hippocampus, amygdala, and temporal-occipital neocortex. Copyright 2009 Wiley-Liss, Inc

Upregulation of GH, but not IGF1, in the hippocampus of the lactating dam after kainic acid injury

PubMed Central

Arellanes-Licea, Elvira C; Ávila-Mendoza, José; Ramírez-Martínez, Elizabeth C; Ramos, Eugenia; Uribe-González, Nancy; Arámburo, Carlos

2018-01-01

Lactation embodies a natural model of morphological, neurochemical, and functional brain plasticity. In this reproductive stage, the hippocampus of the female is less sensitive to excitotoxins in contrast to nulliparity. Growth hormone (GH) and insulin-like growth factor 1 (IGF1) are known to be neuroprotective in several experimental models of brain lesion. Here, activation of the GH–IGF1 pituitary–brain axis following kainic acid (7.5 mg/kg i.p. KA) lesion was studied in lactating and nulliparous rats. Serum concentrations of GH and IGF1 were uncoupled in lactation. Compared to virgin rats, the basal concentration of GH increased up to 40% but IGF1 decreased 58% in dams, and only GH increased further after KA treatment. In the hippocampus, basal expression of GH mRNA was higher (2.8-fold) in lactating rats than in virgin rats. GH mRNA expression in lactating rats increased further after KA administration in the hippocampus and in the hypothalamus, in parallel to GH protein concentration in the hippocampus of KA-treated lactating rats (43% vs lactating control), as detected by Western blot and immunofluorescence. Except for the significantly lower mRNA concentration in the liver of lactating rats, IGF1 expression was not altered by the reproductive condition or by KA treatment in the hippocampus and hypothalamus. Present results indicate upregulation of GH expression in the hippocampus after an excitotoxic lesion, suggesting paracrine/autocrine actions of GH as a factor underlying neuroprotection in the brain of the lactating dam. Since no induction of IGF1 was detected, present data suggest a direct action of GH. PMID:29321175

Hippocampal and cerebellar atrophy in patients with Cushing's disease.

PubMed

Burkhardt, Till; Lüdecke, Daniel; Spies, Lothar; Wittmann, Linus; Westphal, Manfred; Flitsch, Jörg

2015-11-01

OBJECT Cushing's disease (CD) may cause atrophy of different regions of the human brain, mostly affecting the hippocampus and the cerebellum. This study evaluates the use of 3-T MRI of newly diagnosed patients with CD to detect atrophic degeneration with voxel-based volumetry. METHODS Subjects with newly diagnosed, untreated CD were included and underwent 3-T MRI. Images were analyzed using a voxelwise statistical test to detect reduction of brain parenchyma. In addition, an atlas-based volumetric study for regions likely to be affected by CD was performed. RESULTS Nineteen patients with a mean disease duration of 24 months were included. Tumor markers included adrenocorticotropic hormone (median 17.5 pmol/L), cortisol (949.4 nmol/L), and dehydroepiandrosterone sulfate (5.4 μmol/L). The following values are expressed as the mean ± SD. The voxelwise statistical test revealed clusters of significantly reduced gray matter in the hippocampus and cerebellum, with volumes of 2.90 ± 0.26 ml (right hippocampus), 2.89 ± 0.28 ml (left hippocampus), 41.95 ± 4.67 ml (right cerebellar hemisphere), and 42.11 ± 4.59 ml (left cerebellar hemisphere). Healthy control volunteers showed volumes of 3.22 ± 0.25 ml for the right hippocampus, 3.23 ± 0.25 ml for the left hippocampus, 50.87 ± 4.23 ml for the right cerebellar hemisphere, and 50.42 ± 3.97 ml for the left cerebellar hemisphere. CONCLUSIONS Patients with untreated CD show significant reduction of gray matter in the cerebellum and hippocampus. These changes can be analyzed and objectified with the quantitative voxel-based method described in this study.

Retrieval-Induced Upregulation of Tet3 in Pyramidal Neurons of the Dorsal Hippocampus Mediates Cocaine-Associated Memory Reconsolidation.

PubMed

Liu, Cao; Sun, Xue; Wang, Zhilin; Le, Qiumin; Liu, Peipei; Jiang, Changyou; Wang, Feifei; Ma, Lan

2018-03-01

Memory retrieval refers to reexposure to information previously encoded and stored in the brain. Following retrieval, a once-consolidated memory destabilizes and undergoes reconsolidation, during which gene expression changes to restabilize memory. Investigating epigenetic regulation during reconsolidation could provide insights into normal memory formation and pathological memory associated with psychiatric disorders. We used cocaine-induced conditioned place preference to assess the cocaine-associated memory of mice and used chemogenetic methods to manipulate the activity of the pyramidal neurons in the dorsal hippocampus. We isolated the ribosome-associated transcripts from the excitatory neurons in the dorsal hippocampus by RiboTag purification to identify the potential epigenetic regulators, and we specifically knocked down gene expression in pyramidal neurons with a Cre-dependent lentivirus. Chemogenetically silencing the activity of the pyramidal neurons in the dorsal hippocampus immediately after memory retrieval markedly impaired memory reconsolidation, and the ribosome-associated mRNA level of the ten-eleven translocation (Tet) family methylcytosine dioxygenase Tet3, but not Tet1 or Tet2, was dramatically upregulated 10 minutes after memory retrieval. The protein level of Tet3 in the dorsal hippocampus but not in the anterior cingulate cortex was dramatically increased 1 hour after memory retrieval. Specifically, knockdown of Tet3 in pyramidal neurons in the dorsal hippocampus decreased the activation of pyramidal neurons and impaired the reconsolidation of cocaine-associated memory. Our findings highlight the new function of the DNA demethylation regulator Tet3 in pyramidal neurons of the dorsal hippocampus in regulating the reconsolidation of cocaine-associated memory. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Different Simultaneous Sleep States in the Hippocampus and Neocortex

PubMed Central

Emrick, Joshua J.; Gross, Brooks A.; Riley, Brett T.; Poe, Gina R.

2016-01-01

Study Objectives: Investigators assign sleep-waking states using brain activity collected from a single site, with the assumption that states occur at the same time throughout the brain. We sought to determine if sleep-waking states differ between two separate structures: the hippocampus and neocortex. Methods: We measured electrical signals (electroencephalograms and electromyograms) during sleep from the hippocampus and neocortex of five freely behaving adult male rats. We assigned sleep-waking states in 10-sec epochs based on standard scoring criteria across a 4-h recording, then analyzed and compared states and signals from simultaneous epochs between sites. Results: We found that the total amount of each state, assigned independently using the hippocampal and neocortical signals, was similar between the hippocampus and neocortex. However, states at simultaneous epochs were different as often as they were the same (P = 0.82). Furthermore, we found that the progression of states often flowed through asynchronous state-pairs led by the hippocampus. For example, the hippocampus progressed from transition-to-rapid eye movement sleep to rapid eye movement sleep before the neocortex more often than in synchrony with the neocortex (38.7 ± 16.2% versus 15.8 ± 5.6% mean ± standard error of the mean). Conclusions: We demonstrate that hippocampal and neocortical sleep-waking states often differ in the same epoch. Consequently, electrode location affects estimates of sleep architecture, state transition timing, and perhaps even percentage of time in sleep states. Therefore, under normal conditions, models assuming brain state homogeneity should not be applied to the sleeping or waking brain. Citation: Emrick JJ, Gross BA, Riley BT, Poe GR. Different simultaneous sleep states in the hippocampus and neocortex. SLEEP 2016;39(12):2201–2209. PMID:27748240

Neuregulin 1 Deficiency Modulates Adolescent Stress-Induced Dendritic Spine Loss in a Brain Region-Specific Manner and Increases Complement 4 Expression in the Hippocampus.

PubMed

Clarke, David J; Chohan, Tariq W; Kassem, Mustafa S; Smith, Kristie L; Chesworth, Rose; Karl, Tim; Kuligowski, Michael P; Fok, Sandra Y; Bennett, Maxwell R; Arnold, Jonathon C

2018-03-16

One neuropathological feature of schizophrenia is a diminished number of dendritic spines in the prefrontal cortex and hippocampus. The neuregulin 1 (Nrg1) system is involved in the plasticity of dendritic spines, and chronic stress decreases dendritic spine densities in the prefrontal cortex and hippocampus. Here, we aimed to assess whether Nrg1 deficiency confers vulnerability to the effects of adolescent stress on dendritic spine plasticity. We also assessed other schizophrenia-relevant neurobiological changes such as microglial cell activation, loss of parvalbumin (PV) interneurons, and induction of complement factor 4 (C4). Adolescent male wild-type (WT) and Nrg1 heterozygous mice were subjected to chronic restraint stress before their brains underwent Golgi impregnation or immunofluorescent staining of PV interneurons, microglial cells, and C4. Stress in WT mice promoted dendritic spine loss and microglial cell activation in the prefrontal cortex and the hippocampus. However, Nrg1 deficiency rendered mice resilient to stress-induced dendritic spine loss in the infralimbic cortex and the CA3 region of the hippocampus without affecting stress-induced microglial cell activation in these brain regions. Nrg1 deficiency and adolescent stress combined to trigger increased dendritic spine densities in the prelimbic cortex. In the hippocampal CA1 region, Nrg1 deficiency accentuated stress-induced dendritic spine loss. Nrg1 deficiency increased C4 protein and decreased C4 mRNA expression in the hippocampus, and the number of PV interneurons in the basolateral amygdala. This study demonstrates that Nrg1 modulates the impact of stress on the adolescent brain in a region-specific manner. It also provides first evidence of a link between Nrg1 and C4 systems in the hippocampus.

Gender differences and lateralization in the distribution pattern of insulin-like growth factor-1 receptor in developing rat hippocampus: an immunohistochemical study.

PubMed

Hami, Javad; Kheradmand, Hamed; Haghir, Hossein

2014-03-01

Numerous investigators have provided data supporting essential roles for insulin-like growth factor-I (IGF-I) in development of the brain. The aim of this study was to immunohistochemically determine the distinct regional distribution pattern of IGF-1 receptor (IGF-IR) expression in various portions of newborn rat hippocampus on postnatal days 0 (P0), 7 (P7), and 14 (P14), with comparison between male/female and right/left hippocampi. We found an overall significant increase in distribution of IGF-IR-positive (IGF-IR+) cells in CA1 from P0 until P14. Although, no marked changes in distribution of IGF-IR+ cells in areas CA2 and CA3 were observed; IGF-IR+ cells in DG decreased until P14. The smallest number of immunoreactive cells was present in CA2 and the highest number in DG at P0. Moreover, in CA1, CA3, and DG, the number of IGF-IR+ cells was markedly higher in both sides of the hippocampus in females. Our data also showed a higher mean number of IGF-IR+ cells in the left hippocampus of female at P7. By contrast, male pups showed a significantly higher number of IGF-IR+ cells in the DG of the right hippocampus. At P14, the mean number of immunoreactive cells in CA1, CA3, and DG areas found to be significantly increased in left side of hippocampus of males, compared to females. These results indicate the existence of a differential distribution pattern of IGF-IR between left-right and male-female hippocampi. Together with other mechanisms, these differences may underlie sexual dimorphism and left-right asymmetry in the hippocampus.

Anisomycin administered in the olfactory bulb and dorsal hippocampus impaired social recognition memory consolidation in different time-points.

PubMed

Pena, R R; Pereira-Caixeta, A R; Moraes, M F D; Pereira, G S

2014-10-01

To identify an individual as familiar, rodents form a specific type of memory named social recognition memory. The olfactory bulb (OB) is an important structure for social recognition memory, while the hippocampus recruitment is still controversial. The present study was designed to elucidate the OB and the dorsal hippocampus contribution to the consolidation of social memory. For that purpose, we tested the effect of anisomycin (ANI), which one of the effects is the inhibition of protein synthesis, on the consolidation of social recognition memory. Swiss adult mice with cannulae implanted into the CA1 region of the dorsal hippocampus or into the OB were exposed to a juvenile during 5 min (training session; TR), and once again 1.5 h or 24 h later to test social short-term memory (S-STM) or social long-term memory (S-LTM), respectively. To study S-LTM consolidation, mice received intra-OB or intra-CA1 infusion of saline or ANI immediately, 3, 6 or 18 h after TR. ANI impaired S-LTM consolidation in the OB, when administered immediately or 6h after TR. In the dorsal hippocampus, ANI was amnesic only if administered 3 h after TR. Furthermore, the infusion of ANI in either OB or CA1, immediately after training, did not affect S-STM. Moreover, ANI administered into the OB did not alter the animal's performance in the buried food-finding task. Altogether, our results suggest the consolidation of S-LTM requires both OB and hippocampus participation, although in different time points. This study may help shedding light on the specific roles of the OB and dorsal hippocampus in social recognition memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Obesity Weighs down Memory through a Mechanism Involving the Neuroepigenetic Dysregulation of Sirt1

PubMed Central

Heyward, Frankie D.; Gilliam, Daniel; Coleman, Mark A.; Gavin, Cristin F.; Wang, Jing; Kaas, Garrett; Trieu, Richard; Lewis, John; Moulden, Jerome

2016-01-01

Aberrant gene expression within the hippocampus has recently been implicated in the pathogenesis of obesity-induced memory impairment. Whether a dysregulation of epigenetic modifications mediates this disruption in gene transcription has yet to be established. Here we report evidence of obesity-induced alterations in DNA methylation of memory-associated genes, including Sirtuin 1 (Sirt1), within the hippocampus, and thus offer a novel mechanism by which SIRT1 expression within the hippocampus is suppressed during obesity. Forebrain neuron-specific Sirt1 knock-out closely recapitulated the memory deficits exhibited by obese mice, consistent with the hypothesis that the high-fat diet-mediated reduction of hippocampal SIRT1 could be responsible for obesity-linked memory impairment. Obese mice fed a diet supplemented with the SIRT1-activating molecule resveratrol exhibited increased hippocampal SIRT1 activity and preserved hippocampus-dependent memory, further strengthening this conclusion. Thus, our findings suggest that the memory-impairing effects of diet-induced obesity may potentially be mediated by neuroepigenetic dysregulation of SIRT1 within the hippocampus. SIGNIFICANCE STATEMENT Previous studies have implicated transcriptional dysregulation within the hippocampus as being a relevant pathological concomitant of obesity-induced memory impairment, yet a deeper understanding of the basis for, and etiological significance of, transcriptional dysregulation in this context is lacking. Here we present the first evidence of epigenetic dysregulation (i.e., altered DNA methylation and hydroxymethylation) of memory-related genes, including Sirt1, within the hippocampus of obese mice. Furthermore, experiments using transgenic and pharmacological approaches strongly implicate reduced hippocampal SIRT1 as being a principal pathogenic mediator of obesity-induced memory impairment. This paper offers a novel working model that may serve as a conceptual basis for the development of therapeutic interventions for obesity-induced memory impairment. PMID:26818519

Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.

2010-11-15

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume wasmore » 3.3 cm{sup 3}, occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy{sub 2} using helical tomotherapy and by 81% to 0.73 Gy{sub 2} using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.« less

Systems Reconsolidation Reveals a Selective Role for the Anterior Cingulate Cortex in Generalized Contextual Fear Memory Expression

PubMed Central

Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim

2015-01-01

After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory. PMID:25091528

Systems reconsolidation reveals a selective role for the anterior cingulate cortex in generalized contextual fear memory expression.

PubMed

Einarsson, Einar Ö; Pors, Jennifer; Nader, Karim

2015-01-01

After acquisition, hippocampus-dependent memories undergo a systems consolidation process, during which they become independent of the hippocampus and dependent on the anterior cingulate cortex (ACC) for memory expression. However, consolidated remote memories can become transiently hippocampus-dependent again following memory reactivation. How this systems reconsolidation affects the role of the ACC in remote memory expression is not known. Using contextual fear conditioning, we show that the expression of 30-day-old remote memory can transiently be supported by either the ACC or the dorsal hippocampus following memory reactivation, and that the ACC specifically mediates expression of remote generalized contextual fear memory. We found that suppression of neural activity in the ACC with the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) impaired the expression of remote, but not recent, contextual fear memory. Fear expression was not affected by this treatment if preceded by memory reactivation 6 h earlier, nor was it affected by suppression of neural activity in the dorsal hippocampus with the GABA-receptor agonist muscimol. However, simultaneous targeting of both the ACC and the dorsal hippocampus 6 h after memory reactivation disrupted contextual fear memory expression. Second, we observed that expression of a 30-day-old generalized contextual fear memory in a novel context was not affected by memory reactivation 6 h earlier. However, intra-ACC CNQX infusion before testing impaired contextual fear expression in the novel context, but not the original training context. Together, these data suggest that although the dorsal hippocampus may be recruited during systems reconsolidation, the ACC remains necessary for the expression of generalized contextual fear memory.

MDMA administration decreases serotonin but not N-acetylaspartate in the rat brain

PubMed Central

Perrine, Shane A.; Ghoddoussi, Farhad; Michaels, Mark S.; Hyde, Elisabeth M.; Kuhn, Donald M.; Galloway, Matthew P.

2010-01-01

In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton magnetic resonance spectroscopy (1H-MRS) at 11.7 Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5 mg/kg IP, 4× q 2 h) or saline and euthanized 7 days after the last injection. Monoamine content was measured with HPLC in contralateral punches from striatum and hippocampus to compare the MDMA-induced loss of 5HT innervation with constituents in the 1H-MRS profile. When assessed 7 days after the last MDMA injection, levels of hippocampal and striatal serotonin (5HT) were significantly reduced, consistent with published animal studies. N-acetylaspartate (NAA) levels were significantly increased in prefrontal cortex and not affected in anterior striatum or hippocampus; myo-inositol (INS) levels were increased in prefrontal cortex and hippocampus but not anterior striatum. Glutamate levels were increased in prefrontal cortex and decreased in hippocampus, while GABA levels were decreased only in hippocampus. The data suggest that NAA may not reliably reflect MDMA-induced 5HT neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate and GABA is consistent with persistent hippocampal neuroadaptations caused by MDMA. PMID:20800616

Brain regions involved in the retrieval of spatial and episodic details associated with a familiar environment: an fMRI study.

PubMed

Hirshhorn, Marnie; Grady, Cheryl; Rosenbaum, R Shayna; Winocur, Gordon; Moscovitch, Morris

2012-11-01

Functional magnetic resonance imaging (fMRI) was used to compare brain activity during the retrieval of coarse- and fine-grained spatial details and episodic details associated with a familiar environment. Long-time Toronto residents compared pairs of landmarks based on their absolute geographic locations (requiring either coarse or fine discriminations) or based on previous visits to those landmarks (requiring episodic details). An ROI analysis of the hippocampus showed that all three conditions activated the hippocampus bilaterally. Fine-grained spatial judgments recruited an additional region of the right posterior hippocampus, while episodic judgments recruited an additional region of the right anterior hippocampus, and a more extensive region along the length of the left hippocampus. To examine whole-brain patterns of activity, Partial Least Squares (PLS) analysis was used to identify sets of brain regions whose activity covaried with the three conditions. All three comparison judgments recruited the default mode network including the posterior cingulate/retrosplenial cortex, middle frontal gyrus, hippocampus, and precuneus. Fine-grained spatial judgments also recruited additional regions of the precuneus, parahippocampal cortex and the supramarginal gyrus. Episodic judgments recruited the posterior cingulate and medial frontal lobes as well as the angular gyrus. These results are discussed in terms of their implications for theories of hippocampal function and spatial and episodic memory. Copyright © 2012 Elsevier Ltd. All rights reserved.

Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission.

PubMed

Kouser, Mehreen; Speed, Haley E; Dewey, Colleen M; Reimers, Jeremy M; Widman, Allie J; Gupta, Natasha; Liu, Shunan; Jaramillo, Thomas C; Bangash, Muhammad; Xiao, Bo; Worley, Paul F; Powell, Craig M

2013-11-20

The Shank3 gene encodes a scaffolding protein that anchors multiple elements of the postsynaptic density at the synapse. Previous attempts to delete the Shank3 gene have not resulted in a complete loss of the predominant naturally occurring Shank3 isoforms. We have now characterized a homozygous Shank3 mutation in mice that deletes exon 21, including the Homer binding domain. In the homozygous state, deletion of exon 21 results in loss of the major naturally occurring Shank3 protein bands detected by C-terminal and N-terminal antibodies, allowing us to more definitively examine the role of Shank3 in synaptic function and behavior. This loss of Shank3 leads to an increased localization of mGluR5 to both synaptosome and postsynaptic density-enriched fractions in the hippocampus. These mice exhibit a decrease in NMDA/AMPA excitatory postsynaptic current ratio in area CA1 of the hippocampus, reduced long-term potentiation in area CA1, and deficits in hippocampus-dependent spatial learning and memory. In addition, these mice also exhibit motor-coordination deficits, hypersensitivity to heat, novelty avoidance, altered locomotor response to novelty, and minimal social abnormalities. These data suggest that Shank3 isoforms are required for normal synaptic transmission/plasticity in the hippocampus, as well as hippocampus-dependent spatial learning and memory.

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

PubMed

Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

Matrix Metalloproteinase 9 Displays a Particular Time Response to Acute Stress: Variation in Its Levels and Activity Distribution in Rat Hippocampus.

PubMed

Aguayo, Felipe I; Pacheco, Aníbal A; García-Rojo, Gonzalo J; Pizarro-Bauerle, Javier A; Doberti, Ana V; Tejos, Macarena; García-Pérez, María A; Rojas, Paulina S; Fiedler, Jenny L

2018-05-16

A single stress exposure facilitates memory formation through neuroplastic processes that reshape excitatory synapses in the hippocampus, probably requiring changes in extracellular matrix components. We tested the hypothesis that matrix metalloproteinase 9 (MMP-9), an enzyme that degrades components of extracellular matrix and synaptic proteins such as β-dystroglycan (β-DG 43 ), changes their activity and distribution in rat hippocampus during the acute stress response. After 2.5 h of restraint stress, we found (i) increased MMP-9 levels and potential activity in whole hippocampal extracts, accompanied by β-DG 43 cleavage, and (ii) a significant enhancement of MMP-9 immunoreactivity in dendritic fields such as stratum radiatum and the molecular layer of hippocampus. After 24 h of stress, we found that (i) MMP-9 net activity rises at somatic field, i.e., stratum pyramidale and granule cell layers, and also at synaptic field, mainly stratum radiatum and the molecular layer of hippocampus, and (ii) hippocampal synaptoneurosome fractions are enriched with MMP-9, without variation of its potential enzymatic activity, in accordance with the constant level of cleaved β-DG 43 . These findings indicate that stress triggers a peculiar timing response in the MMP-9 levels, net activity, and subcellular distribution in the hippocampus, suggesting its involvement in the processing of substrates during the stress response.

MDMA administration decreases serotonin but not N-acetylaspartate in the rat brain.

PubMed

Perrine, Shane A; Ghoddoussi, Farhad; Michaels, Mark S; Hyde, Elisabeth M; Kuhn, Donald M; Galloway, Matthew P

2010-12-01

In animals, repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) reduces markers of serotonergic activity and studies show similar serotonergic deficits in human MDMA users. Using proton-magnetic resonance spectroscopy ((1)H-MRS) at 11.7Tesla, we measured the metabolic neurochemical profile in intact, discrete tissue punches taken from prefrontal cortex, anterior striatum, and hippocampus of rats administered MDMA (5mg/kg IP, 4× q 2h) or saline and euthanized 7 days after the last injection. Monoamine content was measured with HPLC in contralateral punches from striatum and hippocampus to compare the MDMA-induced loss of 5HT innervation with constituents in the (1)H-MRS profile. When assessed 7 days after the last MDMA injection, levels of hippocampal and striatal serotonin (5HT) were significantly reduced, consistent with published animal studies. N-Acetylaspartate (NAA) levels were significantly increased in prefrontal cortex and not affected in anterior striatum or hippocampus; myo-inositol (INS) levels were increased in prefrontal cortex and hippocampus but not anterior striatum. Glutamate levels were increased in prefrontal cortex and decreased in hippocampus, while GABA levels were decreased only in hippocampus. The data suggest that NAA may not reliably reflect MDMA-induced 5HT neurotoxicity. However, the collective pattern of changes in 5HT, INS, glutamate and GABA is consistent with persistent hippocampal neuroadaptations caused by MDMA. Copyright © 2010 Elsevier Inc. All rights reserved.

Vagus nerve stimulation enhances perforant path-CA3 synaptic transmission via the activation of β-adrenergic receptors and the locus coeruleus.

PubMed

Shen, Huilian; Fuchino, Yuta; Miyamoto, Daisuke; Nomura, Hiroshi; Matsuki, Norio

2012-05-01

Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and depression and has cognition-enhancing effects in patients with Alzheimer's disease. The hippocampus is widely recognized to be related to epilepsy, depression, and Alzheimer's disease. One possible mechanism of VNS involves its effect on the hippocampus; i.e. it increases the release of noradrenaline in the hippocampus. However, the effect of VNS on synaptic transmission in the hippocampus is unknown. To determine whether VNS modulates neurotransmission in the hippocampus, we examined the effects of VNS on perforant path (PP)-CA3 synaptic transmission electrophysiologically in anaesthetized rats. VNS induces a persistent enhancement of PP-CA3 field excitatory post-synaptic potentials (fEPSPs). Arc, an immediate early gene, was used to identify active brain regions after VNS. The locus coeruleus (LC), which contains the perikarya of noradrenergic projections, harboured more Arc-positive cells, as measured by in-situ hybridization, after 10-min VNS. In addition, electrical lesions of LC neurons or intraventricular administration of the β-adrenergic receptor antagonist timolol prevented the enhancement of PP-CA3 responses by VNS. In conclusion, the protracted increase in PP-CA3 synaptic transmission that is induced by VNS entails activation of the LC and β-adrenergic receptors. Our novel findings suggest that information from the periphery modulates synaptic transmission in the CA3 region of the hippocampus.

Damage to Hippocampus of Rats after Being Exposed to Infrasound.

PubMed

Zhang, Meng Yao; Chen, Chen; Xie, Xue Jun; Xu, Sheng Long; Guo, Guo Zhen; Wang, Jin

2016-06-01

The objective was to observe damage of hippocampus in rats after exposure to infrasound, and to assess HSP70 expression in hippocampus. SD rats in the experimental group were exposed to 140 dB (8 Hz) infrasound for 2 h per day for 3 days. The morphology of the hippocampus was examined by transmission electronic microscopic (TEM). Cell apoptosis was observed by TUNEL staining at 0 h, 24 h, 48 h, and 2 w after exposure. HSP70 expression was detected by immunohistochemistry (IHC) and Western blotting (WB). TEM showed that hippocampus was significantly damaged by exposure, and exhibited recovery 1 week after exposure. The TUNEL data showed that neuronal apoptosis after exposure was significantly higher than in the control rats at 24 h and 48 h, and the apoptotic cells decreased one week after exposure. IHC and WB showed HSP70 expression was significantly higher in the exposed rats, peaked at 24 h. Exposure to 140 dB (8 Hz) infrasound for 2 h per day for 3 days appeared to induce damage to the hippocampus of rats, based on changes in ultrastructure and increased cell apoptosis. However, recovery from the damage occurred overtime. HSP70 expression also increased after the exposure and decreased by 48. Copyright © 2016 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Complementary learning systems within the hippocampus: a neural network modelling approach to reconciling episodic memory with statistical learning

PubMed Central

Turk-Browne, Nicholas B.; Botvinick, Matthew M.; Norman, Kenneth A.

2017-01-01

A growing literature suggests that the hippocampus is critical for the rapid extraction of regularities from the environment. Although this fits with the known role of the hippocampus in rapid learning, it seems at odds with the idea that the hippocampus specializes in memorizing individual episodes. In particular, the Complementary Learning Systems theory argues that there is a computational trade-off between learning the specifics of individual experiences and regularities that hold across those experiences. We asked whether it is possible for the hippocampus to handle both statistical learning and memorization of individual episodes. We exposed a neural network model that instantiates known properties of hippocampal projections and subfields to sequences of items with temporal regularities. We found that the monosynaptic pathway—the pathway connecting entorhinal cortex directly to region CA1—was able to support statistical learning, while the trisynaptic pathway—connecting entorhinal cortex to CA1 through dentate gyrus and CA3—learned individual episodes, with apparent representations of regularities resulting from associative reactivation through recurrence. Thus, in paradigms involving rapid learning, the computational trade-off between learning episodes and regularities may be handled by separate anatomical pathways within the hippocampus itself. This article is part of the themed issue ‘New frontiers for statistical learning in the cognitive sciences’. PMID:27872368

Complementary learning systems within the hippocampus: a neural network modelling approach to reconciling episodic memory with statistical learning.

PubMed

Schapiro, Anna C; Turk-Browne, Nicholas B; Botvinick, Matthew M; Norman, Kenneth A

2017-01-05

A growing literature suggests that the hippocampus is critical for the rapid extraction of regularities from the environment. Although this fits with the known role of the hippocampus in rapid learning, it seems at odds with the idea that the hippocampus specializes in memorizing individual episodes. In particular, the Complementary Learning Systems theory argues that there is a computational trade-off between learning the specifics of individual experiences and regularities that hold across those experiences. We asked whether it is possible for the hippocampus to handle both statistical learning and memorization of individual episodes. We exposed a neural network model that instantiates known properties of hippocampal projections and subfields to sequences of items with temporal regularities. We found that the monosynaptic pathway-the pathway connecting entorhinal cortex directly to region CA1-was able to support statistical learning, while the trisynaptic pathway-connecting entorhinal cortex to CA1 through dentate gyrus and CA3-learned individual episodes, with apparent representations of regularities resulting from associative reactivation through recurrence. Thus, in paradigms involving rapid learning, the computational trade-off between learning episodes and regularities may be handled by separate anatomical pathways within the hippocampus itself.This article is part of the themed issue 'New frontiers for statistical learning in the cognitive sciences'. © 2016 The Author(s).

Memory Consolidation

PubMed Central

Squire, Larry R.; Genzel, Lisa; Wixted, John T.; Morris, Richard G.

2015-01-01

Conscious memory for a new experience is initially dependent on information stored in both the hippocampus and neocortex. Systems consolidation is the process by which the hippocampus guides the reorganization of the information stored in the neocortex such that it eventually becomes independent of the hippocampus. Early evidence for systems consolidation was provided by studies of retrograde amnesia, which found that damage to the hippocampus-impaired memories formed in the recent past, but typically spared memories formed in the more remote past. Systems consolidation has been found to occur for both episodic and semantic memories and for both spatial and nonspatial memories, although empirical inconsistencies and theoretical disagreements remain about these issues. Recent work has begun to characterize the neural mechanisms that underlie the dialogue between the hippocampus and neocortex (e.g., “neural replay,” which occurs during sharp wave ripple activity). New work has also identified variables, such as the amount of preexisting knowledge, that affect the rate of consolidation. The increasing use of molecular genetic tools (e.g., optogenetics) can be expected to further improve understanding of the neural mechanisms underlying consolidation. PMID:26238360

Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus

PubMed Central

Evuarherhe, Obaro; Barker, Gareth R. I.; Savalli, Giorgia; Warburton, Elizabeth C.; Brown, Malcolm W.

2014-01-01

Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesised to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluR2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluR2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluR2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. PMID:24729442

Hippocampal arterial cerebral blood volume in early psychosis

PubMed Central

Talati, Pratik; Rane, Swati; Donahue, Manus J.; Heckers, Stephan

2016-01-01

Recent studies of patients in the early stage of psychosis have revealed increased cerebral blood volume (CBV) in specific subfields of the anterior hippocampus. These studies required injection of a contrast agent to measure steady state CBV. Here we used a novel, non-invasive method, inflow-based-vascular-space-occupancy with dynamic subtraction (iVASO-DS), to measure the arterial component of CBV (aCBV) in a single slice of the hippocampus. Based on evidence from contrast-enhanced CBV studies, we hypothesized increased aCBV in the anterior hippocampus in early psychosis. We used 3T MRI to generate iVASO-derived aCBV maps in 17 medicated patients (average duration of illness = 7.6 months) and 25 matched controls. We did not find hemispheric or regional group differences in hippocampal aCBV. The limited spatial resolution of the iVASO-DS method did not allow us to test for aCBV differences in specific subfields of the hippocampus. Future studies should investigate venous and arterial CBV changes in the hippocampus of early psychosis patients. PMID:27644028

FoxO6 regulates memory consolidation and synaptic function

PubMed Central

Salih, Dervis A.M.; Rashid, Asim J.; Colas, Damien; de la Torre-Ubieta, Luis; Zhu, Ruo P.; Morgan, Alexander A.; Santo, Evan E.; Ucar, Duygu; Devarajan, Keerthana; Cole, Christina J.; Madison, Daniel V.; Shamloo, Mehrdad; Butte, Atul J.; Bonni, Azad; Josselyn, Sheena A.; Brunet, Anne

2012-01-01

The FoxO family of transcription factors is known to slow aging downstream from the insulin/IGF (insulin-like growth factor) signaling pathway. The most recently discovered FoxO isoform in mammals, FoxO6, is highly enriched in the adult hippocampus. However, the importance of FoxO factors in cognition is largely unknown. Here we generated mice lacking FoxO6 and found that these mice display normal learning but impaired memory consolidation in contextual fear conditioning and novel object recognition. Using stereotactic injection of viruses into the hippocampus of adult wild-type mice, we found that FoxO6 activity in the adult hippocampus is required for memory consolidation. Genome-wide approaches revealed that FoxO6 regulates a program of genes involved in synaptic function upon learning in the hippocampus. Consistently, FoxO6 deficiency results in decreased dendritic spine density in hippocampal neurons in vitro and in vivo. Thus, FoxO6 may promote memory consolidation by regulating a program coordinating neuronal connectivity in the hippocampus, which could have important implications for physiological and pathological age-dependent decline in memory. PMID:23222102

Effects of aniracetam on extracellular levels of transmitter amino acids in the hippocampus of the conscious gerbils: an intracranial microdialysis study.

PubMed

Yu, Siming; Cai, Jingxia

2003-03-27

The effects of aniracetam on extracellular amino acid levels in the hippocampus of conscious gerbils, with or without transient cerebral ischemia/reperfusion, were measured by microdialysis and reverse phase-high performance liquid chromatography. Increased extracellular levels of aspartate and glutamate that were observed in the hippocampus of conscious gerbils during transient global forebrain ischemia were reversed by aniracetam. In contrast, the level of extracellular gamma-aminobutyric acid was increased, while taurine was maintained at a higher level than other amino acids by administration of aniracetam (100 mg/kg, p.o.) 60 min before ischemia. Further, in contrast to ischemic animals, administration of aniracetam (100 mg/kg, p.o.) enhanced the release of glutamate and aspartate in the normal gerbil hippocampus. The results suggest that these effects might be due to a partial calcium agonist activity of aniracetam, and that the effects of aniracetam on amino acid levels might be a mechanism of protection against delayed neuronal death in the ischemic hippocampus, thereby improving memory dysfunction induced by ischemia/reperfusion.

Total neuron numbers in CA1-4 sectors of the dog hippocampus.

PubMed

Rağbetli, Murat Cetin; Aydinlioğlu, Atif; Koyun, Necat; Yayici, Recep; Arslan, Kadir

2010-06-01

Early reports addressed morphological asymmetry in the cross-sectional width of the rat hippocampus. The present study was aimed at counting total number of neurons in CA1-4 sectors and the subiculum of the dog hippocampus as well as investigating possible left /right and male/female asymmetry. Adult mongrel dogs (8 female and 5 male) were assessed by the right and left pawedness and sacrificed by exsanguinations. In each hippocampus dissected, the total neuron numbers of CAs and subiculum were estimated by the physical fractioning method. Significant hemispheric asymmetries were found in the number of pyramidal cells of CA1, CA3/2, CA4 and the subiculum. Sex difference was also found in the subiculum, in favour of the males. Our study indicated a left dominant asymmetry in males and right dominancy in females as well as no functional asymmetry in specific regions of the dog hippocampus. Further investigations are necessary to verify the hypothesis that hippocampal morphological asymmetries in normal subjects are functionally related in memory or in cognitive skills.

An update on contextual fear memory mechanisms: Transition between Amygdala and Hippocampus.

PubMed

Chaaya, Nicholas; Battle, Andrew R; Johnson, Luke R

2018-05-09

Context is an ever-present combination of discrete environmental elements capable of influencing many psychological processes. When context is associated with an aversive stimulus, a permanent contextual fear memory is formed. Context is hypothesized to greatly influence the treatability of various fear-based pathologies, in particular, post-traumatic stress disorder (PTSD). In order to understand how contextual fear memories are encoded and impact underlying fear pathology, delineation of the underlying neural circuitry of contextual fear memory consolidation and maintenance is essential. Past understandings of contextual fear suggest that the hippocampus only creates a unitary, or single, representation of context. This representation is sent to the amygdala, which creates the associative contextual fear memory. In contrast, here we review new evidence from the literature showing contextual fear memories to be consolidated and maintained by both amygdala and hippocampus. Based on this evidence, we revise the current model of contextual fear memory consolidation, highlighting a larger role for hippocampus. This new model may better explain the role of the hippocampus in PTSD. Copyright © 2018 Elsevier Ltd. All rights reserved.

Melatonin prevents memory impairment induced by high-fat diet: Role of oxidative stress.

PubMed

Alzoubi, Karem H; Mayyas, Fadia A; Mahafzah, Rania; Khabour, Omar F

2018-01-15

Consumption of high-fat diet (HFD) induces oxidative stress in the hippocampus that leads to memory impairment. Melatonin has antioxidant and neuroprotective effects. In this study, we hypothesized that chronic administration of melatonin can prevent memory impairment induced by consumption of HFD. Melatonin was administered to rats via oral gavage (100mg/kg/day) for 4 weeks. HFD was also instituted for the same duration. Behavioral studies were conducted to test spatial memory using the radial arm water maze. Additionally, oxidative stress biomarkers were assessed in the hippocampus. Results showed that HFD impaired both short- and long- term memory (P<0.05), while melatonin treatment prevented such effects. Furthermore, melatonin prevented HFD-induced reduction in levels of GSH, and ratio of GSH/GSSG, and increase in GSSG in the hippocampus. Melatonin also prevented reduction in the catalase activity in hippocampus of animals on HFD. In conclusion, HFD induced memory impairment and melatonin prevented this impairment probably by preventing alteration of oxidative stress in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

PubMed

Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

2017-08-03

Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review

PubMed Central

Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-ya

2017-01-01

Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity. PMID:28771175

Functional Convergence of Neurons Generated in the Developing and Adult Hippocampus

PubMed Central

Piatti, Verónica C; Morgenstern, Nicolás A; Zhao, Chunmei; van Praag, Henriette; Gage, Fred H; Schinder, Alejandro F

2006-01-01

The dentate gyrus of the hippocampus contains neural progenitor cells (NPCs) that generate neurons throughout life. Developing neurons of the adult hippocampus have been described in depth. However, little is known about their functional properties as they become fully mature dentate granule cells (DGCs). To compare mature DGCs generated during development and adulthood, NPCs were labeled at both time points using retroviruses expressing different fluorescent proteins. Sequential electrophysiological recordings from neighboring neurons of different ages were carried out to quantitatively study their major synaptic inputs: excitatory projections from the entorhinal cortex and inhibitory afferents from local interneurons. Our results show that DGCs generated in the developing and adult hippocampus display a remarkably similar afferent connectivity with regard to both glutamate and GABA, the major neurotransmitters. We also demonstrate that adult-born neurons can fire action potentials in response to an excitatory drive, exhibiting a firing behavior comparable to that of neurons generated during development. We propose that neurons born in the developing and adult hippocampus constitute a functionally homogeneous neuronal population. These observations are critical to understanding the role of adult neurogenesis in hippocampal function. PMID:17121455

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

PubMed Central

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-01-01

Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

PubMed

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-12-01

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

Serotonin Receptors in Hippocampus

PubMed Central

Berumen, Laura Cristina; Rodríguez, Angelina; Miledi, Ricardo; García-Alcocer, Guadalupe

2012-01-01

Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a functional network that uses several serotonin receptors to regulate their roles in this particular part of the limbic system. PMID:22629209

Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A totalmore » of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Algan, O; Giem, J; Young, J

Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-testmore » analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.« less

Comparison of doses received by the hippocampus in patients treated with single isocenter- vs multiple isocenter-based stereotactic radiation therapy to the brain for multiple brain metastases.

PubMed

Algan, Ozer; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

2015-01-01

To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)-based or multiple isocenter (MI)-based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V100. All of the other measured dosimetric parameters including the V95, V99, and D100 were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Interplay of hippocampus and prefrontal cortex in memory

PubMed Central

Preston, Alison R.; Eichenbaum, Howard

2013-01-01

Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

Diseases of captive yellow seahorse Hippocampus kuda Bleeker, pot-bellied seahorse Hippocampus abdominalis Lesson and weedy seadragon Phyllopteryx taeniolatus (Lacépède).

PubMed

LePage, V; Young, J; Dutton, C J; Crawshaw, G; Paré, J A; Kummrow, M; McLelland, D J; Huber, P; Young, K; Russell, S; Al-Hussinee, L; Lumsden, J S

2015-05-01

Seahorses, pipefish and seadragons are fish of the Family Syngnathidae. From 1998 to 2010, 172 syngnathid cases from the Toronto Zoo were submitted for post-mortem diagnostics and retrospectively examined. Among the submitted species were yellow seahorses Hippocampus kuda Bleeker (n=133), pot-bellied seahorses Hippocampus abdominalis Lesson (n=35) and weedy seadragons Phyllopteryx taeniolatus (Lacépède; n=4). The three most common causes of morbidity and mortality in this population were bacterial dermatitis, bilaterally symmetrical myopathy and mycobacteriosis, accounting for 24%, 17% and 15% of cases, respectively. Inflammatory processes were the most common diagnoses, present in 117 cases. Seven neoplasms were diagnosed, environmental aetiologies were identified in 46 cases, and two congenital defects were identified. © 2014 John Wiley & Sons Ltd.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum.

PubMed

Goldfarb, Elizabeth V; Chun, Marvin M; Phelps, Elizabeth A

2016-01-20

Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory.

Memory-Guided Attention: Independent Contributions of the Hippocampus and Striatum

PubMed Central

Goldfarb, Elizabeth V.; Chun, Marvin M.; Phelps, Elizabeth A.

2015-01-01

SUMMARY Memory can strongly influence how attention is deployed in future encounters. Though memory dependent on the medial temporal lobes has been shown to drive attention, how other memory systems could concurrently and comparably enhance attention is less clear. Here, we demonstrate that both reinforcement learning and context memory facilitate attention in a visual search task. Using functional magnetic resonance imaging, we dissociate the mechanisms by which these memories guide attention: trial by trial, the hippocampus (not the striatum) predicted attention benefits from context memory, while the striatum (not the hippocampus) predicted facilitation from rewarded stimulus-response associations. Responses in these regions were also distinctly correlated with individual differences in each type of memory-guided attention. This study provides novel evidence for the role of the striatum in guiding attention, dissociable from hippocampus-dependent context memory. PMID:26777274

Proteolytic Degradation of SCOP in the Hippocampus Contributes to Activation of MAP Kinase and Memory

PubMed Central

Shimizu, Kimiko; Phan, Trongha; Mansuy, Isabelle; Storm, Daniel R.

2007-01-01

Summary Because activation of Erk1/2 MAP kinase (MAPK) is critical for hippocampus-dependent memory, there is considerable interest in mechanisms for regulation of MAPK during memory formation. Here we report that MAPK and CREB-mediated transcription are negatively regulated by SCOP (SCN Circadian Oscillatory Protein) and that SCOP is proteolyzed by calpain when hippocampal neurons are stimulated by BDNF, KCl depolarization, or NMDA. Moreover, training for novel object memory decreases SCOP in the hippocampus. To determine if hippocampus-dependent memory is influenced by SCOP in vivo, we generated a transgenic mouse strain for the inducible overexpression of SCOP in the forebrain. Overexpression of SCOP completely blocked memory for novel objects. We conclude that degradation of SCOP by calpain contributes to activation of MAPK during memory formation. PMID:17382888

Context-dependent memory following recurrent hypoglycaemia in non-diabetic rats is mediated via glucocorticoid signalling in the dorsal hippocampus.

PubMed

Osborne, Danielle M; O'Leary, Kelsey E; Fitzgerald, Dennis P; George, Alvin J; Vidal, Michael M; Anderson, Brian M; McNay, Ewan C

2017-01-01

Recurrent hypoglycaemia is primarily caused by repeated over-administration of insulin to patients with diabetes. Although cognition is impaired during hypoglycaemia, restoration of euglycaemia after recurrent hypoglycaemia is associated with improved hippocampally mediated memory. Recurrent hypoglycaemia alters glucocorticoid secretion in response to hypoglycaemia; glucocorticoids are well established to regulate hippocampal processes, suggesting a possible mechanism for recurrent hypoglycaemia modulation of subsequent cognition. We tested the hypothesis that glucocorticoids within the dorsal hippocampus might mediate the impact of recurrent hypoglycaemia on hippocampal cognitive processes. We characterised changes in the dorsal hippocampus at several time points to identify specific mechanisms affected by recurrent hypoglycaemia, using a well-validated 3 day model of recurrent hypoglycaemia either alone or with intrahippocampal delivery of glucocorticoid (mifepristone) and mineralocorticoid (spironolactone) receptor antagonists prior to each hypoglycaemic episode. Recurrent hypoglycaemia enhanced learning and also increased hippocampal expression of glucocorticoid receptors, serum/glucocorticoid-regulated kinase 1, cyclic AMP response element binding (CREB) phosphorylation, and plasma membrane levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA) receptors. Both hippocampus-dependent memory enhancement and the molecular changes were reversed by glucocorticoid receptor antagonist treatment. These results indicate that increased glucocorticoid signalling during recurrent hypoglycaemia produces several changes in the dorsal hippocampus that are conducive to enhanced hippocampus-dependent contextual learning. These changes appear to be adaptive, and in addition to supporting cognition may reduce damage otherwise caused by repeated exposure to severe hypoglycaemia.

Gonadectomy reduces the density of androgen receptor-immunoreactive neurons in male rat's hippocampus: testosterone replacement compensates it.

PubMed

Moghadami, Sajjad; Jahanshahi, Mehrdad; Sepehri, Hamid; Amini, Hossein

2016-01-28

In the present study, the role of gonadectomy on memory impairment and the density of androgen receptor-immunoreactive neurons in rats' hippocampus as well as the ability of testosterone to compensate of memory and the density of androgen receptors in the hippocampus was evaluated. Adult male rats (except intact-no testosterone group) were bilaterally castrated, and behavioral tests performed 2 weeks later. Animals bilaterally cannulated into lateral ventricles and then received testosterone (10, 40 and 120 µg/0.5 µl DMSO) or vehicle (DMSO; 0.5 µl) for gonadectomized-vehicle group, 30 min before training in water maze test. The androgen receptor-immunoreactive neurons were detected by immunohistochemical technique in the hippocampal areas. In the gonadectomized male rats, a memory deficit was found in Morris water maze test on test day (5th day) after DMSO administration. Gonadectomy decreased density of androgen receptor-immunoreactive neurons in the rats' hippocampus. The treatment with testosterone daily for 5 days attenuated memory deficits induced by gonadectomy. Testosterone also significantly increased the density of androgen receptor-immunoreactive neurons in the hippocampal areas. The intermediate dose of this hormone (40 µg) appeared to have a significant effect on spatial memory and the density of androgen receptor-immunoreactive neurons in gonadectomized rats' hippocampus. The present study suggests that testosterone can compensate memory failure in gonadectomized rats. Also testosterone replacement can compensate the reduction of androgen receptor-immunoreactive neurons density in the rats' hippocampus after gonadectomy.

Effect of thyroxine on munc-18 and syntaxin-1 expression in dorsal hippocampus of adult-onset hypothyroid rats

PubMed Central

Zhu, Y.; Ning, D.; Wang, F.; Liu, C.; Xu, Y.; Jia, X.; Zhu, D.

2012-01-01

Adult-onset hypothyroidism induces a variety of impairments on hippocampus- dependent neurocognitive functioningin which many synaptic proteins in hippocampus neurons are involved. Here, we observed the effect of adult-onset hypothyroidism on the expression of syntaxin-1 and munc-18 in the dorsal hippocampus and whether the altered proteins could be restored by levothyroxine (T4) treatment. All rats were separated into 4 groups randomly: hypothyroid group, 5 µg T4 /100 g body weight (BW) treated group, 20 µg T4/100 g BW treated group and control group. The radioimmunoassay kits were applied to assay the levels of serum T3 and T4, and the levels of syntaxin-1 and munc-18 in hippocampus were assessed by immunohistochemistry and Western blot. Both analysis corroborated that syntaxin-1 in the hypothyroid group was significantly higher. Munc-18 was lower in four layers of CA3 and dentate gyrus by immunohistochemistry. After two weeks of treatment with 5 µg T4/100 g BW for hypothyroidism, syntaxin-1 levels were completely restored, whereas the recovery of munc-18 only located in two of the four impaired layers. Twenty µg T4/100 g BW treatment normalized munc-18 levels. These data suggested that adult-onset hypothyroidism induced increment of syntaxin-1 and decrement of munc-18 in the dorsal hippocampus, which could be restored by T4 treatment. Larger dosage of T4 caused more effective restorations. PMID:22688303

Novel Experience Induces Persistent Sleep-Dependent Plasticity in the Cortex but not in the Hippocampus

PubMed Central

Ribeiro, Sidarta; Shi, Xinwu; Engelhard, Matthew; Zhou, Yi; Zhang, Hao; Gervasoni, Damien; Lin, Shi-Chieh; Wada, Kazuhiro; Lemos, Nelson A.M.

2007-01-01

Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS) and rapid eye movement (REM) sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP), and expression levels of plasticity-related immediate-early genes (IEG) arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours) than in the hippocampus (minutes). During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10–14 Hz) but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time. PMID:18982118

A Brain System for Auditory Working Memory.

PubMed

Kumar, Sukhbinder; Joseph, Sabine; Gander, Phillip E; Barascud, Nicolas; Halpern, Andrea R; Griffiths, Timothy D

2016-04-20

The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. Copyright © 2016 Kumar et al.

Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

NASA Astrophysics Data System (ADS)

Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

2016-05-01

The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

Effects of prolonged abstinence from METH on the hippocampal BDNF levels, neuronal numbers and apoptosis in methamphetamine-sensitized rats.

PubMed

Hajheidari, Samira; Sameni, Hamid Reza; Bandegi, Ahmad Reza; Miladi-Gorji, Hossein

2017-04-03

Methamphetamine (METH) use is associated with neuronal damage in various regions of brain, while effects of prolonged abstinence on METH-induced damage are not quite clear. This study evaluated serum and hippocampal BDNF levels, neuronal numbers and apoptosis in METH-sensitized and abstinent rats. Rats were sensitized to METH (2mg/kg, daily/18 days, s.c.). All rats were evaluated for neuron counting, the TUNEL test and serum and hippocampal BDNF levels after 30 days of forced abstinence from METH. The results showed that increased BDNF levels in the hippocampus and serum of METH-sensitized rats returned to control level after 30 days of abstinence. The number of neurons in the DG and CA1 of hippocampus and also, the total hippocampal perimeter and area in METH-sensitized rats were significantly lower than the saline rats. While, the number of neurons was not significantly increased in the hippocampus after prolonged abstinence from METH. Also, METH-sensitized rats showed a significant increase in TUNEL-positive cells, whereas METH-abstinent rats showed a slight but significant decrease in TUNEL-positive cells in the DG and CA3 of hippocampus. These results suggest that despite the reduction in BDNF levels, reducing the number of neurons, perimeter and area of the hippocampus were stable after abstinence. Thus, the degenerative effects of METH have been sustained even after prolonged abstinence in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Seahorses of the Hippocampus coronatus complex: taxonomic revision, and description of Hippocampus haema, a new species from Korea and Japan (Teleostei, Syngnathidae).

PubMed

Han, Sang-Yun; Kim, Jin-Koo; Kai, Yoshiaki; Senou, Hiroshi

2017-01-01

Morphological and molecular analyses were conducted on 182 specimens belonging to the Hippocampus coronatus complex ( H. coronatus sensu lato), collected in Korea and Japan 1933-2015, in order to clarify the taxonomic status of the species within this complex. Three species are recognized based on the shape of the coronet, the number of trunk rings (TrR) and tail rings (TaR), and presence or absence of a wing-tip spine (WS) at the dorsal fin base. Hippocampus coronatus Temminck & Schlegel, 1850 ( H. coronatus sensu stricto), is diagnosed by 10 TrR, 37-40 TaR, an extremely high coronet (55.7-79.0 % head length) with four tips on the corona flat (CoT), and one WS. Hippocampus sindonis Jordan & Snyder, 1901 is diagnosed by 10 TrR, 35-38 TaR, a moderately high coronet (36.3-55.4 % HL) with five CoT, and no WS. A new species, H. haema is described on the basis of 140 specimens, characterized by 10 TrR, 35-38 TaR, a moderately high coronet (34.1-54.9 % head length) with four CoT, and two WS. Hippocampus haema is only known from the Korea Strait, western Kyushu, and East/Japan Sea. Recognition of the three species is supported by differences in mitochondrial DNA fragments (cytochrome b , 16S rRNA, and 12S rRNA).

Neurocomputational account of memory and perception: Thresholded and graded signals in the hippocampus.

PubMed

Elfman, Kane W; Aly, Mariam; Yonelinas, Andrew P

2014-12-01

Recent evidence suggests that the hippocampus, a region critical for long-term memory, also supports certain forms of high-level visual perception. A seemingly paradoxical finding is that, unlike the thresholded hippocampal signals associated with memory, the hippocampus produces graded, strength-based signals in perception. This article tests a neurocomputational model of the hippocampus, based on the complementary learning systems framework, to determine if the same model can account for both memory and perception, and whether it produces the appropriate thresholded and strength-based signals in these two types of tasks. The simulations showed that the hippocampus, and most prominently the CA1 subfield, produced graded signals when required to discriminate between highly similar stimuli in a perception task, but generated thresholded patterns of activity in recognition memory. A threshold was observed in recognition memory because pattern completion occurred for only some trials and completely failed to occur for others; conversely, in perception, pattern completion always occurred because of the high degree of item similarity. These results offer a neurocomputational account of the distinct hippocampal signals associated with perception and memory, and are broadly consistent with proposals that CA1 functions as a comparator of expected versus perceived events. We conclude that the hippocampal computations required for high-level perceptual discrimination are congruous with current neurocomputational models that account for recognition memory, and fit neatly into a broader description of the role of the hippocampus for the processing of complex relational information. © 2014 Wiley Periodicals, Inc.

The Anterior Thalamus is Critical for Overcoming Interference in a Context-Dependent Odor Discrimination Task

PubMed Central

Law, L. Matthew; Smith, David M.

2012-01-01

The anterior thalamus (AT) is anatomically interconnected with the hippocampus and other structures known to be involved in memory, and the AT is involved in many of the same learning and memory functions as the hippocampus. For example, like the hippocampus, the AT is involved in spatial cognition and episodic memory. The hippocampus also has a well-documented role in contextual memory processes, but it is not known whether the AT is similarly involved in contextual memory. In the present study, we assessed the role of the AT in contextual memory processes by temporarily inactivating the AT and training rats on a recently developed context-based olfactory list learning task, which was designed to assess the use of contextual information to resolve interference. Rats were trained on one list of odor discrimination problems, followed by training on a second list in either the same context or a different context. In order to induce interference, some of the odors appeared on both lists with their predictive value reversed. Control rats that learned the two lists in different contexts performed significantly better than rats that learned the two lists in the same context. However, AT lesions completely abolished this contextual learning advantage, a result that is very similar to the effects of hippocampal inactivation. These findings demonstrate that the AT, like the hippocampus, is involved in contextual memory and suggest that the hippocampus and AT are part of a functional circuit involved in contextual memory. PMID:23025833

The toxic influence of dibromoacetic acid on the hippocampus and pre-frontal cortex of rat: involvement of neuroinflammation response and oxidative stress.

PubMed

Jiang, Wenbo; Li, Bai; Chen, Yingying; Gao, Shuying

2017-12-01

Dibromoacetic acid (DBA) exsits in drinking water as a by-product of disinfection as a result of chlorination or ozonation processes. Hippocampus and pre-frontal cortex are the key structures in memory formation and weanling babies are more sensitive to environmental toxicant than adults, so this study was conducted to evaluate the potential neurotoxicity effects of DBA exposure when administered intragastrically for 4 weeks to weanling Sprague-Dawley rats, at concentration of 0, 20, 50, 125 mg/kg via the neurobehavioral and neurochemical effects. Results indicated that animals weight gain and food consumption were not significantly affected by DBA. However, morris water maze test showed varying degrees of changes between control and high-dose group. Additionally, the level of malondialdehyde (MDA) and generation of reactive oxygen species (ROS) in the hippocampus and pre-frontal cortex of rats increased significantly. The activities of total superoxide dismutase (SOD) and the glutathione (GSH) content in the hippocampus and pre-frontal cortex of rats decreased significantly after treatment with DBA. Treatment with DBA increased the protein and mRNA expression of Iba-1, NF-κB, TNF-α, IL-6, IL-1β and HO-1 in the hippocampus and pre-frontal cortex of rats. These data suggested that DBA had a toxic influence on the hippocampus and pre-frontal cortex of rats, and that the mechanism of toxicity might be associated with the neuroinflammation response and oxidative stress.

The relationship between level of processing and hippocampal-cortical functional connectivity during episodic memory formation in humans.

PubMed

Schott, Björn H; Wüstenberg, Torsten; Wimber, Maria; Fenker, Daniela B; Zierhut, Kathrin C; Seidenbecher, Constanze I; Heinze, Hans-Jochen; Walter, Henrik; Düzel, Emrah; Richardson-Klavehn, Alan

2013-02-01

New episodic memory traces represent a record of the ongoing neocortical processing engaged during memory formation (encoding). Thus, during encoding, deep (semantic) processing typically establishes more distinctive and retrievable memory traces than does shallow (perceptual) processing, as assessed by later episodic memory tests. By contrast, the hippocampus appears to play a processing-independent role in encoding, because hippocampal lesions impair encoding regardless of level of processing. Here, we clarified the neural relationship between processing and encoding by examining hippocampal-cortical connectivity during deep and shallow encoding. Participants studied words during functional magnetic resonance imaging and freely recalled these words after distraction. Deep study processing led to better recall than shallow study processing. For both levels of processing, successful encoding elicited activations of bilateral hippocampus and left prefrontal cortex, and increased functional connectivity between left hippocampus and bilateral medial prefrontal, cingulate and extrastriate cortices. Successful encoding during deep processing was additionally associated with increased functional connectivity between left hippocampus and bilateral ventrolateral prefrontal cortex and right temporoparietal junction. In the shallow encoding condition, on the other hand, pronounced functional connectivity increases were observed between the right hippocampus and the frontoparietal attention network activated during shallow study processing. Our results further specify how the hippocampus coordinates recording of ongoing neocortical activity into long-term memory, and begin to provide a neural explanation for the typical advantage of deep over shallow study processing for later episodic memory. Copyright © 2011 Wiley Periodicals, Inc.

Human Hippocampal Dynamics during Response Conflict.

PubMed

Oehrn, Carina R; Baumann, Conrad; Fell, Juergen; Lee, Hweeling; Kessler, Henrik; Habel, Ute; Hanslmayr, Simon; Axmacher, Nikolai

2015-08-31

Besides its relevance for declarative memory functions, hippocampal activation has been observed during disambiguation of uncertainty and conflict. Uncertainty and conflict may arise on various levels. On the perceptual level, the hippocampus has been associated with signaling of contextual deviance and disambiguation of similar items (i.e., pattern separation). Furthermore, conflicts can occur on the response level. Animal experiments showed a role of the hippocampus for inhibition of prevailing response tendencies and suppression of automatic stimulus-response mappings, potentially related to increased theta oscillations (3-8 Hz). In humans, a recent fMRI study demonstrated hippocampal involvement in approach-avoidance conflicts. However, the more general significance of hippocampal activity for dealing with response conflicts also on a cognitive level is still unknown. Here, we investigated the role of the hippocampus for response conflict in the Stroop task by combining intracranial electroencephalography (iEEG) recordings from the hippocampus of epilepsy patients with region of interest-based fMRI in healthy participants. Both methods revealed converging evidence that the hippocampus is recruited in a regionally specific manner during response conflict. Moreover, our iEEG data show that this activation depends on theta oscillations and is relevant for successful response conflict resolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus.

PubMed

McIntyre, Christa K; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D; Steward, Oswald; Guzowski, John F; McGaugh, James L

2005-07-26

Activation of beta-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the beta-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance.

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus

PubMed Central

McIntyre, Christa K.; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D.; Steward, Oswald; Guzowski, John F.; McGaugh, James L.

2005-01-01

Activation of β-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the β-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance. PMID:16020527

Temporary inhibition of dorsal or ventral hippocampus by muscimol: distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning.

PubMed

Zhang, Wei-Ning; Bast, Tobias; Xu, Yan; Feldon, Joram

2014-04-01

Studies in rats, involving hippocampal lesions and hippocampal drug infusions, have implicated the hippocampus in the modulation of anxiety-related behaviors and conditioned fear. The ventral hippocampus is considered to be more important for anxiety- and fear-related behaviors than the dorsal hippocampus. In the present study, we compared the role of dorsal and ventral hippocampus in innate anxiety and classical fear conditioning in Wistar rats, examining the effects of temporary pharmacological inhibition by the GABA-A agonist muscimol (0.5 ug/0.5 ul/side) in the elevated plus maze and on fear conditioning to a tone and the conditioning context. In the elevated plus maze, dorsal and ventral hippocampal muscimol caused distinct behavioral changes. The effects of ventral hippocampal muscimol were consistent with suppression of locomotion, possibly accompanied by anxiolytic effects, whereas the pattern of changes caused by dorsal hippocampal muscimol was consistent with anxiogenic effects. In contrast, dorsal and ventral hippocampal muscimol caused similar effects in the fear conditioning experiments, disrupting contextual, but not tone, fear conditioning. Copyright © 2013 Elsevier B.V. All rights reserved.

Unconscious relational encoding depends on hippocampus

PubMed Central

Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

2014-01-01

Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

Computer aided solution for segmenting the neuron line in hippocampal microscope images

NASA Astrophysics Data System (ADS)

Albaidhani, Tahseen; Jassim, Sabah; Al-Assam, Hisham

2017-05-01

The brain Hippocampus component is known to be responsible for memory and spatial navigation. Its functionality depends on the status of different blood vessels within the Hippocampus and is severely impaired by Alzheimer's disease as a result blockage of increasing number of blood vessels by accumulation of amyloid-beta (Aβ) protein. Accurate counting of blood vessels within the Hippocampus of mice brain, from microscopic images, is an active research area for the understanding of Alzheimer's disease. Here, we report our work on automatic detection of the Region of Interest, i.e. the region in which blood vessels are located. This area typically falls between the hippocampus edge and the line of neurons within the Hippocampus. This paper proposes a new method to detect and exclude the neuron line to improve the accuracy of blood vessel counting because some neurons on it might lead to false positive cases as they look like blood vessels. Our proposed solution is based on using trainable segmentation approach with morphological operations, taking into account variation in colour, intensity values, and image texture. Experiments on a sufficient number of microscopy images of mouse brain demonstrate the effectiveness of the developed solution in preparation for blood vessels counting.

Intrauterine growth restriction affects the preterm infant's hippocampus.

PubMed

Lodygensky, Gregory A; Seghier, Mohammed L; Warfield, Simon K; Tolsa, Cristina Borradori; Sizonenko, Stephane; Lazeyras, François; Hüppi, Petra S

2008-04-01

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.

Constructing, Perceiving, and Maintaining Scenes: Hippocampal Activity and Connectivity

PubMed Central

Zeidman, Peter; Mullally, Sinéad L.; Maguire, Eleanor A.

2015-01-01

In recent years, evidence has accumulated to suggest the hippocampus plays a role beyond memory. A strong hippocampal response to scenes has been noted, and patients with bilateral hippocampal damage cannot vividly recall scenes from their past or construct scenes in their imagination. There is debate about whether the hippocampus is involved in the online processing of scenes independent of memory. Here, we investigated the hippocampal response to visually perceiving scenes, constructing scenes in the imagination, and maintaining scenes in working memory. We found extensive hippocampal activation for perceiving scenes, and a circumscribed area of anterior medial hippocampus common to perception and construction. There was significantly less hippocampal activity for maintaining scenes in working memory. We also explored the functional connectivity of the anterior medial hippocampus and found significantly stronger connectivity with a distributed set of brain areas during scene construction compared with scene perception. These results increase our knowledge of the hippocampus by identifying a subregion commonly engaged by scenes, whether perceived or constructed, by separating scene construction from working memory, and by revealing the functional network underlying scene construction, offering new insights into why patients with hippocampal lesions cannot construct scenes. PMID:25405941

[The role of RKIP mediated ERK pathway in hippocampus neurons injured by electromagnetic radiation].

PubMed

Zuo, Hong-Yan; Wang, De-Wen; Peng, Rui-Yun; Wang, Shui-Ming; Gao, Ya-Bing; Zhang, Zhi-Yi; Xiao, Feng-Jun

2008-07-01

To study the effects of electromagnetic radiation on RKIP and phosphorylated ERK in primary cultured hippocampus neurons. The inhibitor of MEK U0126 was applied to investigate the role of RKIP mediated ERK pathway in radiation injury. Primary hippocampus neurons were cultured in vitro. X-HPM, S-HPM and EMP were taken as radiation source respectively to establish three cell models exposed to electromagnetic radiation. RKIP and phosphorylated ERK were measured by immunofluorescent labelling and laser scanning confocal microscope. Apoptosis and death fraction of the cells were detected by Annexin V-PI double labelling and flow cytometry. After three kinds of electromagnetic radiation, the expression of RKIP in hippocampus neurons decreased but the expression of phosphorylated ERK increased, and its nuclear translocation occurred. No significant differences were seen between radiation groups. Apoptosis and death fraction of the neurons in U0126 pretreatment groups was significantly lower than that in radiation groups but they were still higher than those in sham-radiation group. The excessive activation of RKIP mediated ERK pathway is one of the important mechanisms for the apoptosis and death of hippocampus neurons induced by electromagnetic radiation. U0126 have some protective effects on radiation injury.

Hyper-hippocampal glycogen induced by glycogen loading with exhaustive exercise.

PubMed

Soya, Mariko; Matsui, Takashi; Shima, Takeru; Jesmin, Subrina; Omi, Naomi; Soya, Hideaki

2018-01-19

Glycogen loading (GL), a well-known type of sports conditioning, in combination with exercise and a high carbohydrate diet (HCD) for 1 week enhances individual endurance capacity through muscle glycogen supercompensation. This exercise-diet combination is necessary for successful GL. Glycogen in the brain contributes to hippocampus-related memory functions and endurance capacity. Although the effect of HCD on the brain remains unknown, brain supercompensation occurs following exhaustive exercise (EE), a component of GL. We thus employed a rat model of GL and examined whether GL increases glycogen levels in the brain as well as in muscle, and found that GL increased glycogen levels in the hippocampus and hypothalamus, as well as in muscle. We further explored the essential components of GL (exercise and/or diet conditions) to establish a minimal model of GL focusing on the brain. Exercise, rather than a HCD, was found to be crucial for GL-induced hyper-glycogen in muscle, the hippocampus and the hypothalamus. Moreover, EE was essential for hyper-glycogen only in the hippocampus even without HCD. Here we propose the EE component of GL without HCD as a condition that enhances brain glycogen stores especially in the hippocampus, implicating a physiological strategy to enhance hippocampal functions.

Prostaglandins are necessary and sufficient to induce contextual fear learning impairments after interleukin-1 beta injections into the dorsal hippocampus

PubMed Central

Hein, A.M.; Stutzman, D.L.; Bland, S.T.; Barrientos, R.M.; Watkins, L.R.; Rudy, J.W.; Maier, S.F.

2008-01-01

The intra-hippocampal administration of interleukin-1β (IL-1β) as well as the induction of elevated but physiological levels of IL-1β within the hippocampus interferes with the formation of long-term memory. There is evidence suggesting that the induction of prostaglandin (PG) formation by IL-1β is involved in impairments in working and spatial memory following IL-1β. The present experiments extend these findings by showing that PGs are responsible for memory deficits in contextual fear conditioning that occur following IL-1β injection into the dorsal hippocampus. Cyclooxygenase (COX) inhibition blocked the disruption in contextual fear conditioning produced by IL-1β and COX inhibition alone also disrupted contextual memory, suggesting an inverted U-shaped relationship between PG levels and memory. In addition to demonstrating the necessity of PGs in IL-1β mediated memory deficits, we also show that PGs injected directly into the dorsal hippocampus are sufficient to impair context memory and significantly reduce post-conditioning levels of BDNF within the hippocampus, suggesting a possible mechanism for the memory-impairing effects of PGs. PMID:18035502

Hippocampus-dependent place learning enables spatial flexibility in C57BL6/N mice

PubMed Central

Kleinknecht, Karl R.; Bedenk, Benedikt T.; Kaltwasser, Sebastian F.; Grünecker, Barbara; Yen, Yi-Chun; Czisch, Michael; Wotjak, Carsten T.

2012-01-01

Spatial navigation is a fundamental capability necessary in everyday life to locate food, social partners, and shelter. It results from two very different strategies: (1) place learning which enables for flexible way finding and (2) response learning that leads to a more rigid “route following.” Despite the importance of knockout techniques that are only available in mice, little is known about mice' flexibility in spatial navigation tasks. Here we demonstrate for C57BL6/N mice in a water-cross maze (WCM) that only place learning enables spatial flexibility and relearning of a platform position, whereas response learning does not. This capability depends on an intact hippocampal formation, since hippocampus lesions by ibotenic acid (IA) disrupted relearning. In vivo manganese-enhanced magnetic resonance imaging revealed a volume loss of ≥60% of the hippocampus as a critical threshold for relearning impairments. In particular the changes in the left ventral hippocampus were indicative of relearning deficits. In summary, our findings establish the importance of hippocampus-dependent place learning for spatial flexibility and provide a first systematic analysis on spatial flexibility in mice. PMID:23293591

The effect of silver nanoparticles on apoptosis and dark neuron production in rat hippocampus

PubMed Central

Bagheri-abassi, Farzaneh; Alavi, Hassan; Mohammadipour, Abbas; Motejaded, Fatemeh; Ebrahimzadeh-bideskan, Alireza

2015-01-01

Objective(s): Silver nanoparticles (Ag-NPs) are used widely in bedding, water purification, tooth paste and toys. These nanoparticles can enter into the body and move into the hippocampus. The aim of this study was to investigate the neurotoxicity of silver nanoparticles in the adult rat hippocampus. Materials and Methods: 12 male Wistar rats were randomly divided into two experimental and control groups (6 rats in each group). Animals in the experimental group received Ag-NPs (30 mg/kg) orally (gavage) for 28 consecutive days. Control group in the same period was treated with distilled water via gavage. At the end of experiment, animals were deeply anesthetized, sacrificed, and their brains were collected from each group. Finally the brain sections were stained using toluidine blue and TUNEL. Then to compare the groups, dark neurons (DNs) and apoptotic neurons were counted by morphometric method. Results: Results showed that the numbers of DNs and apoptotic cells in the CA1, CA2, CA3, and dentate gyrus (DG) of hippocampus significantly increased in the Ag-NPs group in comparison to the control group (P<0.05). Conclusion: Exposure to Ag-NPs can induce dark neuron and apoptotic cells in the hippocampus. PMID:26351553

Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

PubMed Central

Acosta, Gabriela Beatriz; Fernández, María Alejandra; Roselló, Diego Martín; Tomaro, María Luján; Balestrasse, Karina; Lemberg, Abraham

2009-01-01

AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into sham-operated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions. PMID:19533812

Similar effects of substance P on learning and memory function between hippocampus and striatal marginal division

PubMed Central

Yu, Yan; Zeng, Changchun; Shu, Siyun; Liu, Xuemei; Li, Chuhua

2014-01-01

Substance P is an endogenous neurokinin that is present in the central and peripheral nervous systems. The neuropeptide substance P and its high-affinity receptor neurokinin 1 receptor are known to play an important role in the central nervous system in inflammation, blood pressure, motor behavior and anxiety. The effects of substance P in the hippocampus and the marginal division of the striatum on memory remain poorly understood. Compared with the hippocampus as a control, immunofluorescence showed high expression of the substance P receptor, neurokinin 1, in the marginal division of the striatum of normal rats. Unilateral or bilateral injection of an antisense oligonucleotide against neurokinin 1 receptor mRNA in the rat hippocampus or marginal division of the striatum effectively reduced neurokinin 1 receptor expression. Independent of injection site, rats that received this antisense oligonucleotide showed obviously increased footshock times in a Y-maze test. These results indicate that the marginal division of the striatum plays a similar function in learning and memory to the hippocampus, which is a valuable addition to our mechanistic understanding of the learning and memory functions of the marginal division of the striatum. PMID:25206901

Structural Impairments of Hippocampus in Coal Mine Gas Explosion-Related Posttraumatic Stress Disorder

PubMed Central

Lang, Xu; Li, Huabing; Qin, Wen; Yu, Chunshui

2014-01-01

Investigations on hippocampal and amygdalar volume have revealed inconsistent results in patients with posttraumatic stress disorder (PTSD). Little is known about the structural covariance alterations between the hippocampus and amygdala in PTSD. In this study, we evaluated the alteration in the hippocampal and amygdalar volume and their structural covariance in the coal mine gas explosion related PTSD. High resolution T1-weighted magnetic resonance imaging (MRI) was performed on coal mine gas explosion related PTSD male patients (n = 14) and non-traumatized coalminers without PTSD (n = 25). The voxel-based morphometry (VBM) method was used to test the inter-group differences in hippocampal and amygdalar volume as well as the inter-group differences in structural covariance between the ipsilateral hippocampus and amygdala. PTSD patients exhibited decreased gray matter volume (GMV) in the bilateral hippocampi compared to controls (p<0.05, FDR corrected). GMV covariances between the ipsilateral hippocampus and amygdala were significantly reduced in PTSD patients compared with controls (p<0.05, FDR corrected). The coalminers with gas explosion related PTSD had decreased hippocampal volume and structural covariance with the ipsilateral amygdala, suggesting that the structural impairment of the hippocampus may implicate in the pathophysiology of PTSD. PMID:25000505

Soman Induces Ictogenesis in the Amygdala and Interictal Activity in the Hippocampus That Are Blocked by a GluR5 Kainate Receptor Antagonist In Vitro

DTIC Science & Technology

2009-01-01

to organophosphorus nerve agents in- uces brain seizures, which can cause profound brain dam- ge resulting in death or long-term cognitive deficits...The mygdala and the hippocampus are two of the most seizure- rone brain structures, but their relative contribution to the eneration of seizures after...nerve agent exposure is unclear. ere, we report that application of 1 M soman for 30 min, in at coronal brain slices containing both the hippocampus

[The effect of hyperthyroidism on the cognition processes and the state of the glial intermediate filaments in the rat brain].

PubMed

Nedzvets'kyĭ, V S; Nerush, P O

2010-01-01

The effects of hyperthyreosis on oxidative stress, state of glial intermediate filaments and memory were investigated. We observed a significant increase in lipid peroxidation products into both hippocampus and cortex and memory worsening. The changes of GFAP polypeptides was observed in hippocampus and cortex. In group of rats with hyperthyreosis, the content of GFAP in both soluble and filamentous fractions was increased in hippocampus. This data shows, that glial cytoskeleton is reconstructed under thyroid hormone effects.

G9a/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation.

PubMed

Gupta-Agarwal, Swati; Franklin, Aimee V; Deramus, Thomas; Wheelock, Muriah; Davis, Robin L; McMahon, Lori L; Lubin, Farah D

2012-04-18

Learning triggers alterations in gene transcription in brain regions such as the hippocampus and the entorhinal cortex (EC) that are necessary for long-term memory (LTM) formation. Here, we identify an essential role for the G9a/G9a-like protein (GLP) lysine dimethyltransferase complex and the histone H3 lysine 9 dimethylation (H3K9me2) marks it catalyzes, in the transcriptional regulation of genes in area CA1 of the rat hippocampus and the EC during memory consolidation. Contextual fear learning increased global levels of H3K9me2 in area CA1 and the EC, with observable changes at the Zif268, DNMT3a, BDNF exon IV, and cFOS gene promoters, which occurred in concert with mRNA expression. Inhibition of G9a/GLP in the EC, but not in the hippocampus, enhanced contextual fear conditioning relative to control animals. The inhibition of G9a/GLP in the EC induced several histone modifications that include not only methylation but also acetylation. Surprisingly, we found that downregulation of G9a/GLP activity in the EC enhanced H3K9me2 in area CA1, resulting in transcriptional silencing of the non-memory permissive gene COMT in the hippocampus. In addition, synaptic plasticity studies at two distinct EC-CA1 cellular pathways revealed that G9a/GLP activity is critical for hippocampus-dependent long-term potentiation initiated in the EC via the perforant pathway, but not the temporoammonic pathway. Together, these data demonstrate that G9a/GLP differentially regulates gene transcription in the hippocampus and the EC during memory consolidation. Furthermore, these findings support the possibility of a role for G9a/GLP in the regulation of cellular and molecular cross talk between these two brain regions during LTM formation.

Schisantherin A Improves Learning and Memory of Mice with D-Galactose-Induced Learning and Memory Impairment through Its Antioxidation and Regulation of p19/p53/p21/Cyclin D1/CDK4/RB Gene Expressions.

PubMed

Liu, Cong; Sun, Weijing; Li, Ning; Gao, Jiaqi; Yu, Chunyan; Wang, Chunmei; Sun, Jinghui; Jing, Shu; Chen, Jianguang; Li, He

2018-05-31

Schisantherin A (SCA) was evaluated for possible function in restoring the learning and memory impairment induced by D-galactose in mice. ICR mice were treated with D-galactose subcutaneously (220 mg·kg -1 ), and followed by SCA in different doses (1.25, 2.50 and 5.00 mg·kg -1 , administered orally) for 42 days. Effects of SCA on learning and memory were examined by step-through tests and Morris water maze tests. The activity of superoxide dismutase (SOD), the content of malondialdehyde (MDA) in the peripheral blood and hippocampus of mice were assayed by water-soluble tetrazolium-1 (WST-1) and thiobarbituric acid (TBA) methods. The contents of 8 hydroxy deoxy guanosine (8-OHdG) in the hippocampus of mice were detected by immunosorbent assay methods, respectively. Quantitative real-time PCR and Western Blot were respectively used to detect the expression of p19, p53, p21, cyclin D1, CDK4 and RB genes, and the phosphorylation of RB in the hippocampus of mice. We found that SCA significantly improved the learning and memory impairment induced by D-galactose in mice. After SCA treatment, SOD activity was increased and the content of MDA was decreased in both peripheral blood and hippocampus of mice. 8-OHDG content was also decreased in the hippocampus of mice. Furthermore, the expression of p19, p53 and p21 genes was reduced and the expression of cyclin D1 and CDK4 and the phosphorylation of RB protein were elevated in the hippocampus. SCA may improve the learning and memory impairment induced by D-galactose by enhancing the antioxidant capacity, and regulating the expression of p19/p53/p21/cyclinD1/CDK4 genes, and the phosphorylation of RB protein in the hippocampus of mice.

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.

PubMed

Witt, Juri-Alexander; Coras, Roland; Schramm, Johannes; Becker, Albert J; Elger, Christian E; Blümcke, Ingmar; Helmstaedter, Christoph

2014-04-01

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33-0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50-0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. Copyright © 2013 Wiley Periodicals, Inc.

Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy.

PubMed

Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R; Wong, Eric T; Uhlmann, Erik J; Sengupta, Soma; Kasper, Ekkehard M

2015-11-26

Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1-3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.

Long-Term Exercise Is a Potent Trigger for ΔFosB Induction in the Hippocampus along the dorso–ventral Axis

PubMed Central

Nishijima, Takeshi; Kawakami, Masashi; Kita, Ichiro

2013-01-01

Physical exercise improves multiple aspects of hippocampal function. In line with the notion that neuronal activity is key to promoting neuronal functions, previous literature has consistently demonstrated that acute bouts of exercise evoke neuronal activation in the hippocampus. Repeated activating stimuli lead to an accumulation of the transcription factor ΔFosB, which mediates long-term neural plasticity. In this study, we tested the hypothesis that long-term voluntary wheel running induces ΔFosB expression in the hippocampus, and examined any potential region-specific effects within the hippocampal subfields along the dorso–ventral axis. Male C57BL/6 mice were housed with or without a running wheel for 4 weeks. Long-term wheel running significantly increased FosB/ΔFosB immunoreactivity in all hippocampal regions measured (i.e., in the DG, CA1, and CA3 subfields of both the dorsal and ventral hippocampus). Results confirmed that wheel running induced region-specific expression of FosB/ΔFosB immunoreactivity in the cortex, suggesting that the uniform increase in FosB/ΔFosB within the hippocampus is not a non-specific consequence of running. Western blot data indicated that the increased hippocampal FosB/ΔFosB immunoreactivity was primarily due to increased ΔFosB. These results suggest that long-term physical exercise is a potent trigger for ΔFosB induction throughout the entire hippocampus, which would explain why exercise can improve both dorsal and ventral hippocampus-dependent functions. Interestingly, we found that FosB/ΔFosB expression in the DG was positively correlated with the number of doublecortin-immunoreactive (i.e., immature) neurons. Although the mechanisms by which ΔFosB mediates exercise-induced neurogenesis are still uncertain, these data imply that exercise-induced neurogenesis is at least activity dependent. Taken together, our current results suggest that ΔFosB is a new molecular target involved in regulating exercise-induced hippocampal plasticity. PMID:24282574

Biopersistence of PEGylated Carbon Nanotubes Promotes a Delayed Antioxidant Response after Infusion into the Rat Hippocampus

PubMed Central

Dal Bosco, Lidiane; Weber, Gisele E.; Parfitt, Gustavo M.; Cordeiro, Arthur P.; Sahoo, Sangram K.; Fantini, Cristiano; Klosterhoff, Marta C.; Romano, Luis Alberto; Furtado, Clascídia A.; Santos, Adelina P.; Monserrat, José M.; Barros, Daniela M.

2015-01-01

Carbon nanotubes are promising nanomaterials for the diagnosis and treatment of brain disorders. However, the ability of these nanomaterials to cross cell membranes and interact with neural cells brings the need for the assessment of their potential adverse effects on the nervous system. This study aimed to investigate the biopersistence of single-walled carbon nanotubes functionalized with polyethylene glycol (SWCNT-PEG) directly infused into the rat hippocampus. Contextual fear conditioning, Y-maze and open field tasks were performed to evaluate the effects of SWCNT-PEG on memory and locomotor activity. The effects of SWCNT-PEG on oxidative stress and morphology of the hippocampus were assessed 1 and 7 days after infusion of the dispersions at 0.5, 1.0 and 2.1 mg/mL. Raman analysis of the hippocampal homogenates indicates the biopersistence of SWCNT-PEG in the hippocampus 7 days post-injection. The infusion of the dispersions had no effect on the acquisition or persistence of the contextual fear memory; likewise, the spatial recognition memory and locomotor activity were not affected by SWCNT-PEG. Histological examination revealed no remarkable morphological alterations after nanomaterial exposure. One day after the infusion, SWCNT-PEG dispersions at 0.5 and 1.0 mg/mL were able to decrease total antioxidant capacity without modifying the levels of reactive oxygen species or lipid hydroperoxides in the hippocampus. Moreover, SWCNT-PEG dispersions at all concentrations induced antioxidant defenses and reduced reactive oxygen species production in the hippocampus at 7 days post-injection. In this work, we found a time-dependent change in antioxidant defenses after the exposure to SWCNT-PEG. We hypothesized that the persistence of the nanomaterial in the tissue can induce an antioxidant response that might have provided resistance to an initial insult. Such antioxidant delayed response may constitute an adaptive response to the biopersistence of SWCNT-PEG in the hippocampus. PMID:26075787

Role of the parahippocampal cortex in memory for the configuration but not the identity of objects: converging evidence from patients with selective thermal lesions and fMRI

PubMed Central

Bohbot, Véronique D.; Allen, John J. B.; Dagher, Alain; Dumoulin, Serge O.; Evans, Alan C.; Petrides, Michael; Kalina, Miroslav; Stepankova, Katerina; Nadel, Lynn

2015-01-01

The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex (RPH) were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus (RH) or left hippocampus (LH), sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the functional Magnetic Resonance Imaging (fMRI) experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the RPH in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the RPH for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus. PMID:26283949

TEMPORAL PATTERNS OF LIPOPEROXIDATION AND ANTIOXIDANT ENZYMES ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS

PubMed Central

Navigatore Fonzo, Lorena S.; Golini, Rebeca S.; Delgado, Silvia M.; Ponce, Ivana T.; Bonomi, Myrta R.; Rezza, Irma G.; Gimenez, María S.; Anzulovich, Ana C.

2011-01-01

Animals can adapt their behavior to predictable temporal fluctuations in the environment through both, memory-and-learning processes and an endogenous time-keeping mechanism. Hippocampus plays a key role in memory and learning and is especially susceptible to oxidative stress. In compensation, antioxidant enzymes activity, such as Catalase (CAT) and Glutathione peroxidase (GPx), has been detected in this brain region. Daily rhythms of antioxidant enzymes activitiy, as well as of glutathione and lipid peroxides levels, have been described in brain. Here, we investigate day/night variations in lipoperoxidation, CAT and GPx expression and activity, as well as the temporal fluctuations of two key components of the endogenous clock, BMAL1 and PER1, in the rat hippocampus and evaluate to which extent vitamin A deficiency may affect their amplitude or phase. Holtzman male rats from control, vitamin A-deficient and vitamin A-refed groups were sacrificed throughout a 24-h period. Daily levels of clock proteins, lipoperoxidation, CAT and GPx mRNA, protein, and activity, were determined in the rat hippocampus obtained every 4 or 5 h. Gene expression of RARα and RXRβ was also quantified in the hippocampus of the three groups of rats. Our results show significant daily variations of BMAL1 and PER1 protein expression. Rhythmic lipoperoxidation, CAT, and GPx, expression and activity, were also observed in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level, as well as the amplitude of BMAL1 and PER1 daily oscillation, phase-shifted the daily peak of lipoperoxidation, and had a differential effect on the oscillating CAT and GPx mRNA, protein, and activity. Learning how vitamin A deficiency affects the circadian gene expression in the hippocampus may have an impact on the neurobiology, nutritional and chronobiology fields, emphasizing for the first time the importance of nutritional factors, such as dietary micronutrients, in the regulation of circadian parameters in this brain memory-and-learning-related region. PMID:19308957

Training-induced elevations in extracellular lactate in hippocampus and striatum: Dissociations by cognitive strategy and type of reward.

PubMed

Newman, Lori A; Scavuzzo, Claire J; Gold, Paul E; Korol, Donna L

2017-01-01

Recent evidence suggests that astrocytes convert glucose to lactate, which is released from the astrocytes and supports learning and memory. This report takes a multiple memory perspective to test the role of astrocytes in cognition using real-time lactate measurements during learning and memory. Extracellular lactate levels in the hippocampus or striatum were determined with lactate biosensors while rats were learning place (hippocampus-sensitive) or response (striatum-sensitive) versions of T-mazes. In the first experiment, rats were trained on the place and response tasks to locate a food reward. Extracellular lactate levels in the hippocampus increased beyond those of feeding controls during place training but not during response training. However, striatal lactate levels did not increase beyond those of controls when rats were trained on either the place or the response version of the maze. Because food ingestion itself increased blood glucose and brain lactate levels, the contribution of feeding may have confounded the brain lactate measures. Therefore, we conducted a second similar experiment using water as the reward. A very different pattern of lactate responses to training emerged when water was used as the task reward. First, provision of water itself did not result in large increases in either brain or blood lactate levels. Moreover, extracellular lactate levels increased in the striatum during response but not place learning, whereas extracellular lactate levels in the hippocampus did not differ across tasks. The findings from the two experiments suggest that the relative engagement of the hippocampus and striatum dissociates not only by task but also by reward type. The divergent lactate responses of the hippocampus and striatum in place and response tasks under different reward conditions may reflect ethological constraints tied to foraging for food and water. Copyright © 2016 Elsevier Inc. All rights reserved.

Memory and the hippocampus in food-storing birds: a comparative approach.

PubMed

Clayton, N S

1998-01-01

Comparative studies provide a unique source of evidence for the role of the hippocampus in learning and memory. Within birds and mammals, the hippocampal volume of scatter-hoarding species that cache food in many different locations is enlarged, relative to the remainder of the telencephalon, when compared with than that of species which cache food in one larder, or do not cache at all. Do food-storing species show enhanced memory function in association with the volumetric enlargement of the hippocampus? Comparative studies within the parids (titmice and chickadees) and corvids (jays, nutcrackers and magpies), two families of birds which show natural variation in food-storing behavior, suggest that there may be two kinds of memory specialization associated with scatter-hoarding. First, in terms of spatial memory, several scatter-hoarding species have a more accurate and enduring spatial memory, and a preference to rely more heavily upon spatial cues, than that of closely related species which store less food, or none at all. Second, some scatter-hoarding parids and corvids are also more resistant to memory interference. While the most critical component about a cache site may be its spatial location, there is mounting evidence that food-storing birds remember additional information about the contents and status of cache sites. What is the underlying neural mechanism by which the hippocampus learns and remembers cache sites? The current mammalian dogma is that the neural mechanisms of learning and memory are achieved primarily by variations in synaptic number and efficacy. Recent work on the concomitant development of food-storing, memory and the avian hippocampus illustrates that the avian hippocampus may swell or shrivel by as much as 30% in response to presence or absence of food-storing experience. Memory for food caches triggers a dramatic increase in the total number of number of neurons within the avian hippocampus by altering the rate at which these cells are born and die.

c-fos is induced in the hippocampus during consolidation of sexual imprinting in the zebra finch (Taeniopygia guttata).

PubMed

Sadananda, Monika; Bischof, Hans-Joachim

2004-01-01

c-fos was used to mark regions of enhanced neuronal activity during sexual imprinting, an early learning process by which information about the prospective sexual partner is acquired and consolidated. In the present study, we demonstrate that the hippocampus, already known for its specialized spatial memory capacities in navigating pigeons and in food-storing birds, depicts a selective differential c-fos induction in a situation shown to lead to sexual imprinting, that is, exposing previously isolated male birds to a female for 1 h. c-fos induction is lateralized, the left hippocampus showing more c-fos activity than the right. Our results would indicate a role for the hippocampus in the consolidation process of imprinting, probably in the transfer of information to the other telencephalic areas that show alterations in synaptic connectivity as a result of consolidation of sexual imprinting.

Representation of Non-Spatial and Spatial Information in the Lateral Entorhinal Cortex

PubMed Central

Deshmukh, Sachin S.; Knierim, James J.

2011-01-01

Some theories of memory propose that the hippocampus integrates the individual items and events of experience within a contextual or spatial framework. The hippocampus receives cortical input from two major pathways: the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). During exploration in an open field, the firing fields of MEC grid cells form a periodically repeating, triangular array. In contrast, LEC neurons show little spatial selectivity, and it has been proposed that the LEC may provide non-spatial input to the hippocampus. Here, we recorded MEC and LEC neurons while rats explored an open field that contained discrete objects. LEC cells fired selectively at locations relative to the objects, whereas MEC cells were weakly influenced by the objects. These results provide the first direct demonstration of a double dissociation between LEC and MEC inputs to the hippocampus under conditions of exploration typically used to study hippocampal place cells. PMID:22065409

Fornix and retrosplenial contribution to a hippocampo-thalamic circuit underlying conditional learning.

PubMed

Dumont, Julie R; Petrides, Michael; Sziklas, Viviane

2010-05-01

Rats with combined bilateral lesions of the retrosplenial cortex and the fornix or rats with unilateral lesions to the anterior thalamus and the hippocampus, made in opposite hemispheres (disconnection preparation), and combined with unilateral damage of the retrosplenial cortex in either hemisphere, were tested on a spatial-visual conditional learning task in which they learned arbitrary associations between stimuli and the scene in which they were embedded. All experimental groups were impaired in comparison with normal animals. The more severe deficits occurred when (1) both the fornix and the retrosplenial cortex were damaged bilaterally thus depriving the hippocampus both from subcortical interactions via the fornix and retrosplenial-mediated interactions and (2) when, in the crossed lesion preparation, the unilateral retrosplenial lesion was made in the hemisphere with the intact hippocampus, again because this lesion would be maximally disconnecting the hippocampus from functional interaction with the anterior thalamic nucleus and retrosplenial-mediated input.

Hippocampal brain-network coordination during volitional exploratory behavior enhances learning

PubMed Central

Voss, Joel L.; Gonsalves, Brian D.; Federmeier, Kara D.; Tranel, Daniel; Cohen, Neal J.

2010-01-01

Exploratory behaviors during learning determine what is studied and when, helping to optimize subsequent memory performance. We manipulated how much control subjects had over the position of a moving window through which they studied objects and their locations, in order to elucidate the cognitive and neural determinants of exploratory behaviors. Our behavioral, neuropsychological, and neuroimaging data indicate volitional control benefits memory performance, and is linked to a brain network centered on the hippocampus. Increases in correlated activity between the hippocampus and other areas were associated with specific aspects of memory, suggesting that volitional control optimizes interactions among specialized neural systems via the hippocampus. Memory is therefore an active process intrinsically linked to behavior. Furthermore, brain structures typically seen as passive participants in memory encoding (e.g., the hippocampus) are actually part of an active network that controls behavior dynamically as it unfolds. PMID:21102449

Cognitive memory and mapping in a brain-like system for robotic navigation.

PubMed

Tang, Huajin; Huang, Weiwei; Narayanamoorthy, Aditya; Yan, Rui

2017-03-01

Electrophysiological studies in animals may provide a great insight into developing brain-like models of spatial cognition for robots. These studies suggest that the spatial ability of animals requires proper functioning of the hippocampus and the entorhinal cortex (EC). The involvement of the hippocampus in spatial cognition has been extensively studied, both in animal as well as in theoretical studies, such as in the brain-based models by Edelman and colleagues. In this work, we extend these earlier models, with a particular focus on the spatial coding properties of the EC and how it functions as an interface between the hippocampus and the neocortex, as proposed by previous work. By realizing the cognitive memory and mapping functions of the hippocampus and the EC, respectively, we develop a neurobiologically-inspired system to enable a mobile robot to perform task-based navigation in a maze environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

NASA Astrophysics Data System (ADS)

Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

2013-12-01

Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

[Diagnosis of seizures originating in the amygdala and the hippocampus].

PubMed

Padró, L; Rovira, R

1998-02-01

Lesions in the hippocampus of some epileptic patients were first described one hundred and seventy years ago. Since then our knowledge of the relationship between epileptic seizures and temporal lobe lesions has greatly improved. The aim of this paper is to systematize the symptomatology of the hippocampus and amygdala seizures. These seizures may have a great number of different clinical features: special 'loss' or 'impairment of consciousness', epileptic automatisms and autonomic changes. Moreover, at the beginning of seizures some patients have reported experiences having subjective qualities similar to those experienced in everyday life. P Gloor named them 'experiential phenomena' and subdivided them into affective (eg: fear), perceptual (eg: visual hallucinations) and mnemonic (eg: 'déjà vu' illusion). It is very important to know the contribution of the hippocampus and the amygdala to the symptomatology of temporal lobe seizures due to the progress of MRI diagnostic possibilities that are improving the surgical outcome.

Lateralized hippocampal oscillations underlie distinct aspects of human spatial memory and navigation.

PubMed

Miller, Jonathan; Watrous, Andrew J; Tsitsiklis, Melina; Lee, Sang Ah; Sheth, Sameer A; Schevon, Catherine A; Smith, Elliot H; Sperling, Michael R; Sharan, Ashwini; Asadi-Pooya, Ali Akbar; Worrell, Gregory A; Meisenhelter, Stephen; Inman, Cory S; Davis, Kathryn A; Lega, Bradley; Wanda, Paul A; Das, Sandhitsu R; Stein, Joel M; Gorniak, Richard; Jacobs, Joshua

2018-06-21

The hippocampus plays a vital role in various aspects of cognition including both memory and spatial navigation. To understand electrophysiologically how the hippocampus supports these processes, we recorded intracranial electroencephalographic activity from 46 neurosurgical patients as they performed a spatial memory task. We measure signals from multiple brain regions, including both left and right hippocampi, and we use spectral analysis to identify oscillatory patterns related to memory encoding and navigation. We show that in the left but not right hippocampus, the amplitude of oscillations in the 1-3-Hz "low theta" band increases when viewing subsequently remembered object-location pairs. In contrast, in the right but not left hippocampus, low-theta activity increases during periods of navigation. The frequencies of these hippocampal signals are slower than task-related signals in the neocortex. These results suggest that the human brain includes multiple lateralized oscillatory networks that support different aspects of cognition.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

PubMed

Sandoval-Salazar, Cuauhtemoc; Ramírez-Emiliano, Joel; Trejo-Bahena, Aurora; Oviedo-Solís, Cecilia I; Solís-Ortiz, Martha Silvia

2016-02-29

It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Dorsal hippocampus contributes to model-based planning.

PubMed

Miller, Kevin J; Botvinick, Matthew M; Brody, Carlos D

2017-09-01

Planning can be defined as action selection that leverages an internal model of the outcomes likely to follow each possible action. Its neural mechanisms remain poorly understood. Here we adapt recent advances from human research for rats, presenting for the first time an animal task that produces many trials of planned behavior per session, making multitrial rodent experimental tools available to study planning. We use part of this toolkit to address a perennially controversial issue in planning: the role of the dorsal hippocampus. Although prospective hippocampal representations have been proposed to support planning, intact planning in animals with damaged hippocampi has been repeatedly observed. Combining formal algorithmic behavioral analysis with muscimol inactivation, we provide causal evidence directly linking dorsal hippocampus with planning behavior. Our results and methods open the door to new and more detailed investigations of the neural mechanisms of planning in the hippocampus and throughout the brain.

Hippocampal brain-network coordination during volitional exploratory behavior enhances learning.

PubMed

Voss, Joel L; Gonsalves, Brian D; Federmeier, Kara D; Tranel, Daniel; Cohen, Neal J

2011-01-01

Exploratory behaviors during learning determine what is studied and when, helping to optimize subsequent memory performance. To elucidate the cognitive and neural determinants of exploratory behaviors, we manipulated the control that human subjects had over the position of a moving window through which they studied objects and their locations. Our behavioral, neuropsychological and neuroimaging data indicate that volitional control benefits memory performance and is linked to a brain network that is centered on the hippocampus. Increases in correlated activity between the hippocampus and other areas were associated with specific aspects of memory, which suggests that volitional control optimizes interactions among specialized neural systems through the hippocampus. Memory is therefore an active process that is intrinsically linked to behavior. Furthermore, brain structures that are typically seen as passive participants in memory encoding (for example, the hippocampus) are actually part of an active network that controls behavior dynamically as it unfolds.

Firing rate dynamics in the hippocampus induced by trajectory learning.

PubMed

Ji, Daoyun; Wilson, Matthew A

2008-04-30

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state.

An Upside to Reward Sensitivity: The Hippocampus Supports Enhanced Reinforcement Learning in Adolescence.

PubMed

Davidow, Juliet Y; Foerde, Karin; Galván, Adriana; Shohamy, Daphna

2016-10-05

Adolescents are notorious for engaging in reward-seeking behaviors, a tendency attributed to heightened activity in the brain's reward systems during adolescence. It has been suggested that reward sensitivity in adolescence might be adaptive, but evidence of an adaptive role has been scarce. Using a probabilistic reinforcement learning task combined with reinforcement learning models and fMRI, we found that adolescents showed better reinforcement learning and a stronger link between reinforcement learning and episodic memory for rewarding outcomes. This behavioral benefit was related to heightened prediction error-related BOLD activity in the hippocampus and to stronger functional connectivity between the hippocampus and the striatum at the time of reinforcement. These findings reveal an important role for the hippocampus in reinforcement learning in adolescence and suggest that reward sensitivity in adolescence is related to adaptive differences in how adolescents learn from experience. Copyright © 2016 Elsevier Inc. All rights reserved.

Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning

PubMed Central

Wilson, Matthew A.

2008-01-01

The hippocampus is essential for spatial navigation, which may involve sequential learning. However, how the hippocampus encodes new sequences in familiar environments is unknown. To study the impact of novel spatial sequences on the activity of hippocampal neurons, we monitored hippocampal ensembles while rats learned to switch from two familiar trajectories to a new one in a familiar environment. Here, we show that this novel spatial experience induces two types of changes in firing rates, but not locations of hippocampal place cells. First, place-cell firing rates on the two familiar trajectories start to change before the actual behavioral switch to the new trajectory. Second, repeated exposure on the new trajectory is associated with an increased dependence of place-cell firing rates on immediate past locations. The result suggests that sequence encoding in the hippocampus may involve integration of information about the recent past into current state. PMID:18448645

Somatostatin: An endogenous antiepileptic

PubMed Central

Qiu, Cuie

2008-01-01

The neuropeptide somatostatin is highly expressed in brain regions associated with seizures. In hippocampus, SST expression and release is regulated by seizures, and SST-containing neurons within the hilus of the dentate gyrus are sensitive to seizure-induced death. In vivo and in vitro studies suggest that the loss of SST function in the dentate could contribute to epileptogenesis and seizure susceptibility. SST also has inhibitory actions in the CA1 and CA3 hippocampus, indicating this peptide is an important homeostatic regulator throughout the hippocampus. In vivo studies show SST has robust antiepileptic properties, with the major site of action being hippocampus. In rodents, somatostatin receptor subtype 2 (SST2) and SST4 appear to mediate the majority of the antiepileptic actions of SST, with SST2 predominate in rat and SST4 in mouse. Thus SST receptors may be appropriate targets for new antiepileptic drugs, although validation in human tissue is lacking. PMID:18221832

Local Generation and Propagation of Ripples along the Septotemporal Axis of the Hippocampus

PubMed Central

Patel, Jagdish; Schomburg, Erik W.; Berényi, Antal; Fujisawa, Shigeyoshi

2013-01-01

A topographical relationship exists between the septotemporal segments of the hippocampus and their entorhinal–neocortical targets, but the physiological organization of activity along the septotemporal axis is poorly understood. We recorded sharp-wave ripple patterns in rats during sleep from the entire septotemporal axis of the CA1 pyramidal layer. Qualitatively similar ripples emerged at all levels. From the local seed, ripples traveled septally or temporally at a speed of ∼0.35 m/s, and the spatial spread depended on ripple magnitude. Ripples propagated smoothly across the septal and intermediate segments of the hippocampus, but ripples in the temporal segment often remained isolated. These findings show that ripples can combine information from the septal and intermediate hippocampus and transfer integrated signals downstream. In contrast, ripples that emerged in the temporal pole broadcast largely independent information to their cortical and subcortical targets. PMID:24155307

Early-life stress impacts the developing hippocampus and primes seizure occurrence: cellular, molecular, and epigenetic mechanisms

PubMed Central

Huang, Li-Tung

2014-01-01

Early-life stress includes prenatal, postnatal, and adolescence stress. Early-life stress can affect the development of the hypothalamic-pituitary-adrenal (HPA) axis, and cause cellular and molecular changes in the developing hippocampus that can result in neurobehavioral changes later in life. Epidemiological data implicate stress as a cause of seizures in both children and adults. Emerging evidence indicates that both prenatal and postnatal stress can prime the developing brain for seizures and an increase in epileptogenesis. This article reviews the cellular and molecular changes encountered during prenatal and postnatal stress, and assesses the possible link between these changes and increases in seizure occurrence and epileptogenesis in the developing hippocampus. In addititon, the priming effect of prenatal and postnatal stress for seizures and epileptogenesis is discussed. Finally, the roles of epigenetic modifications in hippocampus and HPA axis programming, early-life stress, and epilepsy are discussed. PMID:24574961

Early Life Stress Effects on Glucocorticoid—BDNF Interplay in the Hippocampus

PubMed Central

Daskalakis, Nikolaos P.; De Kloet, Edo Ronald; Yehuda, Rachel; Malaspina, Dolores; Kranz, Thorsten M.

2015-01-01

Early life stress (ELS) is implicated in the etiology of multiple psychiatric disorders. Important biological effects of ELS are manifested in stress-susceptible regions of the hippocampus and are partially mediated by long-term effects on glucocorticoid (GC) and/or neurotrophin signaling pathways. GC-signaling mediates the regulation of stress response to maintain homeostasis, while neurotrophin signaling plays a key role in neuronal outgrowth and is crucial for axonal guidance and synaptic integrity. The neurotrophin and GC-signaling pathways co-exist throughout the central nervous system (CNS), particularly in the hippocampus, which has high expression levels of glucocorticoid-receptors (GR) and mineralocorticoid-receptors (MR) as well as brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase receptor B (TrkB). This review addresses the effects of ELS paradigms on GC- and BDNF-dependent mechanisms and their crosstalk in the hippocampus, including potential implications for the pathogenesis of common stress-related disorders. PMID:26635521

ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

PubMed

Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

2015-02-01

Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

The hippocampus participates in the control of locomotion speed.

PubMed

López Ruiz, J R; Osuna Carrasco, L P; López Valenzuela, C L; Franco Rodríguez, N E; de la Torre Valdovinos, B; Jiménez Estrada, I; Dueñas Jiménez, J M; Dueñas Jiménez, S H

2015-12-17

The hippocampus role in sensory-motor integration remains unclear. In these experiments we study its function in the locomotor control. To establish the connection between the hippocampus and the locomotor system, electrical stimulation in the CA1 region was applied and EMG recordings were obtained. We also evaluated the hindlimbs and forelimbs kinematic patterns in rats with a penetrating injury (PI) in the hippocampus as well as in a cortex-injured group (CI), which served as control. After the PI, tamoxifen a selective estrogen receptor modulator (SERM) that has been described as a neuroprotector and antiinflammatory drug, or vehicle was administered. Electrical stimulation in the hippocampus produces muscle contractions in the contralateral triceps, when 6 Hz or 8 Hz pulse trains were applied. The penetrating injury in the hippocampus reduced the EMG amplitude after the electrical stimulation. At 7 DPI (days post-injury) we observed an increase in the strides speed in all four limbs of the non-treated group, decreasing the correlation percentage of the studied joints. After 15 DPI the strides speed in the non-treated returned to normal. These changes did not occur in the tamoxifen group nor in cortex-injured group. After 30 days, the nontreated group presented a reduction in the number of pyramidal cell layer neurons at the injury site, in comparison to the tam-treated group. The loss of neurons, may cause the interruption of the trisynaptic circuit and changes in the locomotion speed. Tamoxifen preserves the pyramidal neurons after the injury, probably resulting in the strides speed recovery. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Traveling Theta Waves in the Human Hippocampus

PubMed Central

Zhang, Honghui

2015-01-01

The hippocampal theta oscillation is strongly correlated with behaviors such as memory and spatial navigation, but we do not understand its specific functional role. One hint of theta's function came from the discovery in rodents that theta oscillations are traveling waves that allow parts of the hippocampus to simultaneously exhibit separate oscillatory phases. Because hippocampal theta oscillations in humans have different properties compared with rodents, we examined these signals directly using multielectrode recordings from neurosurgical patients. Our findings confirm that human hippocampal theta oscillations are traveling waves, but also show that these oscillations appear at a broader range of frequencies compared with rodents. Human traveling waves showed a distinctive pattern of spatial propagation such that there is a consistent phase spread across the hippocampus regardless of the oscillations' frequency. This suggests that traveling theta oscillations are important functionally in humans because they coordinate phase coding throughout the hippocampus in a consistent manner. SIGNIFICANCE STATEMENT We show for the first time in humans that hippocampal theta oscillations are traveling waves, moving along the length of the hippocampus in a posterior–anterior direction. The existence of these traveling theta waves is important for understanding hippocampal neural coding because they cause neurons at separate positions in the hippocampus to experience different theta phases simultaneously. The theta phase that a neuron measures is a key factor in how that cell represents behavioral information. Therefore, the existence of traveling theta waves indicates that, to fully understand how a hippocampal neuron represents information, it is vital to also account for that cell's location in addition to conventional measures of neural activity. PMID:26354915

A double dissociation of dorsal and ventral hippocampal function on a learning and memory task mediated by the dorso-lateral striatum.

PubMed

McDonald, Robert J; Jones, Jana; Richards, Blake; Hong, Nancy S

2006-09-01

The objectives of this research were to further delineate the neural circuits subserving proposed memory-based behavioural subsystems in the hippocampal formation. These studies were guided by anatomical evidence showing a topographical organization of the hippocampal formation. Briefly, perpendicular to the medial/lateral entorhinal cortex division there is a second system of parallel circuits that separates the dorsal and ventral hippocampus. Recent work from this laboratory has provided evidence that the hippocampus incidentally encodes a context-specific inhibitory association during acquisition of a visual discrimination task. One question that emerges from this dataset is whether the dorsal or ventral hippocampus makes a unique contribution to this newly described function. Rats with neurotoxic lesions of the dorsal or ventral hippocampus were assessed on the acquisition of the visual discrimination task. Following asymptotic performance they were given reversal training in either the same or a different context from the original training. The results showed that the context-specific inhibition effect is mediated by a circuit that includes the ventral but not the dorsal hippocampus. Results from a control procedure showed that rats with either dorso-lateral striatum damage or dorsal hippocampal lesions were impaired on a tactile/spatial discrimination. Taken together, the results represent a double dissociation of learning and memory function between the ventral and dorsal hippocampus. The formation of an incidental inhibitory association was dependent on ventral but not dorsal hippocampal circuitry, and the opposite dependence was found for the spatial component of a tactile/spatial discrimination.

Mesial temporal lobe epilepsy lateralization using SPHARM-based features of hippocampus and SVM

NASA Astrophysics Data System (ADS)

Esmaeilzadeh, Mohammad; Soltanian-Zadeh, Hamid; Jafari-Khouzani, Kourosh

2012-02-01

This paper improves the Lateralization (identification of the epileptogenic hippocampus) accuracy in Mesial Temporal Lobe Epilepsy (mTLE). In patients with this kind of epilepsy, usually one of the brain's hippocampi is the focus of the epileptic seizures, and resection of the seizure focus is the ultimate treatment to control or reduce the seizures. Moreover, the epileptogenic hippocampus is prone to shrinkage and deformation; therefore, shape analysis of the hippocampus is advantageous in the preoperative assessment for the Lateralization. The method utilized for shape analysis is the Spherical Harmonics (SPHARM). In this method, the shape of interest is decomposed using a set of bases functions and the obtained coefficients of expansion are the features describing the shape. To perform shape comparison and analysis, some pre- and post-processing steps such as "alignment of different subjects' hippocampi" and the "reduction of feature-space dimension" are required. To this end, first order ellipsoid is used for alignment. For dimension reduction, we propose to keep only the SPHARM coefficients with maximum conformity to the hippocampus shape. Then, using these coefficients of normal and epileptic subjects along with 3D invariants, specific lateralization indices are proposed. Consequently, the 1536 SPHARM coefficients of each subject are summarized into 3 indices, where for each index the negative (positive) value shows that the left (right) hippocampus is deformed (diseased). Employing these indices, the best achieved lateralization accuracy for clustering and classification algorithms are 85% and 92%, respectively. This is a significant improvement compared to the conventional volumetric method.

Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

PubMed

Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

2015-12-01

Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dynamic Contrast-Enhanced MRI of Gd-albumin Delivery to the Rat Hippocampus In Vivo by Convection-Enhanced Delivery

PubMed Central

Kim, Jung Hwan; Astary, Garrett W.; Nobrega, Tatiana L.; Kantorovich, Svetlana; Carney, Paul R.; Mareci, Thomas H.; Sarntinoranont, Malisa

2013-01-01

Convection enhanced delivery (CED) shows promise in treating neurological diseases due to its ability to circumvent the blood-brain barrier (BBB) and deliver therapeutics directly to the parenchyma of the central nervous system (CNS). Such a drug delivery method may be useful in treating CNS disorders involving the hippocampus such temporal lobe epilepsy and gliomas; however, the influence of anatomical structures on infusate distribution is not fully understood. As a surrogate for therapeutic agents, we used gadolinium-labeled-albumin (Gd-albumin) tagged with Evans blue dye to observe the time dependence of CED infusate distributions into the rat dorsal and ventral hippocampus in vivo with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). For finer anatomical detail, final distribution volumes (Vd) of the infusate were observed with high-resolution T1-weighted MR imaging and light microscopy of fixed brain sections. Dynamic images demonstrated that Gd-albumin preferentially distributed within the hippocampus along neuroanatomical structures with less fluid resistance and less penetration was observed in dense cell layers. Furthermore, significant leakage into adjacent cerebrospinal fluid (CSF) spaces such as the hippocampal fissure, velum interpositum and midbrain cistern occurred toward the end of infusion. Vd increased linearly with infusion volume (Vi) at a mean Vd/Vi ratio of 5.51 ± 0.55 for the dorsal hippocampus infusion and 5.30 ± 0.83 for the ventral hippocampus infusion. This study demonstrated the significant effects of tissue structure and CSF space boundaries on infusate distribution during CED. PMID:22687936

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

PubMed

Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

2015-06-01

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Context-dependent memory following recurrent hypoglycaemia in non-diabetic rats is mediated via glucocorticoid signalling in the dorsal hippocampus

PubMed Central

Osborne, Danielle M.; O'Leary, Kelsey E.; Fitzgerald, Dennis P.; George, Alvin J.; Vidal, Michael M.; Anderson, Brian M.; McNay, Ewan C.

2016-01-01

Aims/hypothesis Recurrent hypoglycaemia is primarily caused by repeated over-administration of insulin to patients with diabetes. Although cognition is impaired during hypoglycaemia, restoration of euglycaemia after recurrent hypoglycaemia is associated with improved hippocampally mediated memory. Recurrent hypoglycaemia alters glucocorticoid secretion in response to hypoglycaemia; glucocorticoids are well established to regulate hippocampal processes, suggesting a possible mechanism for recurrent hypoglycaemia modulation of subsequent cognition. We tested the hypothesis that glucocorticoids within the dorsal hippocampus might mediate the impact of recurrent hypoglycaemia on hippocampal cognitive processes. Methods We characterised changes in the dorsal hippocampus at several time points to identify specific mechanisms affected by recurrent hypoglycaemia, using a well-validated 3 day model of recurrent hypoglycaemia either alone or with intrahippocampal delivery of glucocorticoid (mifepristone) and mineralocorticoid (spironolactone) receptor antagonists prior to each hypoglycaemic episode. Results Recurrent hypoglycaemia enhanced learning and also increased hippocampal expression of glucocorticoid receptors, serum/glucocorticoid-regulated kinase 1, cyclic AMP response element binding (CREB) phosphorylation, and plasma membrane levels of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartic acid (NMDA) receptors. Both hippocampus-dependent memory enhancement and the molecular changes were reversed by glucocorticoid receptor antagonist treatment. Conclusions/interpretation These results indicate that increased glucocorticoid signalling during recurrent hypoglycaemia produces several changes in the dorsal hippocampus that are conducive to enhanced hippocampus-dependent contextual learning. These changes appear to be adaptive, and in addition to supporting cognition may reduce damage otherwise caused by repeated exposure to severe hypoglycaemia. PMID:27681242

Age-related expression of Neurexin1 and Neuroligin3 is correlated with presynaptic density in the cerebral cortex and hippocampus of male mice.

PubMed

Kumar, Dhiraj; Thakur, M K

2015-01-01

Neurexin1 (Nrxn1) and Neuroligin3 (Nlgn3) are cell adhesion proteins, which play an important role in synaptic plasticity that declines with advancing age. However, the expression of these proteins during aging has not been analyzed. In the present study, we have examined the age-related changes in the expression of these proteins in cerebral cortex and hippocampus of 10-, 30-, 50-, and 80-week-old male mice. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis indicated that messenger RNA (mRNA) level of Nrxn1 and Nlgn3 significantly increased from 10 to 30 weeks and then decreased at 50 weeks in both the regions. However, in 80-week-old mice, Nrxn1 and Nlgn3 were further downregulated in cerebral cortex while Nrxn1 was downregulated and Nlgn3 was upregulated in hippocampus. These findings were corroborated by immunoblotting and immunofluorescence results. When the expression of Nrxn1 and Nlgn3 was correlated with presynaptic density marker synaptophysin, it was found that synaptophysin protein expression in cerebral cortex was high at 10 weeks and decreased gradually up to 80 weeks, whereas in hippocampus, it decreased until 50 weeks and then increased remarkably at 80 weeks. Furthermore, Pearson's correlation analysis showed that synaptophysin had a strong relation with Nrxn1 and Nlgn3 in cerebral cortex and with Nlgn3 in hippocampus. Thus, these findings showed that Nrxn1 and Nlgn3 are differentially expressed in cerebral cortex and hippocampus which might be responsible for alterations in synaptic plasticity during aging.

Effects of duloxetine on microRNA expression profile in frontal lobe and hippocampus in a mouse model of depression.

PubMed

Pan, Bing; Liu, Yamei

2015-01-01

Depression is a major mood disorder affecting people worldwide. The posttranscriptional gene regulation mediated by microRNAs (miRNAs) which may have critical roles in the pathogenesis of depression. However, to date, little is known about the effects of the antidepressant drug duloxetine on miRNA expression profile in chronic unpredictable mild stress (CUMS)-induced depression model in mice. Healthy adult male Kunming mice were randomly divided into three groups: control group, model group and duloxetine group. Sucrose preference test and open field test were used to represent the behavioral change. MiRNAs levels in frontal lobe and hippocampus of mice were analyzed using miRNA microarrays assay. We observed that long-term treatment with duloxetine significantly ameliorated the CUMS procedure-induced sucrose preference decreases and mice treated with duloxetine demonstrated a reversal of the number of crossings, and rearings reduced by CUMS. A significant upregulation of miR-132 and miR-18a in hippocampus in the duloxetine treatment group compared with model group, whereas the levels of miR-134 and miR-124a were significantly downregulated. Furthermore, miR-18a showed significant upregulation in frontal lobe in the duloxetine treatment group relative to model group. Our data showed that miRNA expression profile in frontal lobe and hippocampus was affected by duloxetine in mice model of depression. The effect was especially pronounced in the hippocampus, suggesting that hippocampus might be the action site of duloxetine, which presumably worked by regulating the expression of miRNA levels.

Dispersal, habitat differences, and comparative phylogeography of Southeast Asian seahorses (Syngnathidae: Hippocampus).

PubMed

Lourie, S A; Green, D M; Vincent, A C J

2005-04-01

Four distinct phylogeographical patterns across Southeast Asia were observed for four species of seahorse (genus Hippocampus) with differing ecologies. For all species, genetic differentiation (based on cytochrome b sequence comparisons) was significantly associated with sample site (Phi(ST) = 0.190-0.810, P < 0.0001) and with geographical distance (Mantel's r = 0.37-0.59, P < 0.019). Geographic locations of genetic breaks were inconsistent across species in 7/10 comparisons, although some similarities across species were also observed. The two shallow-water species (Hippocampus barbouri and Hippocampus kuda) have colonized the Sunda Shelf to a lesser degree than the two deeper-water species (Hippocampus spinosissimus and Hippocampus trimaculatus). In all species the presence of geographically restricted haplotypes in the Philippines could indicate past population fragmentation and/or long-distance colonization. A nested clade analysis (NCA) revealed that long-distance colonization and/or fragmentation were likely the dominant forces that structure populations of the two shallow-water species, whereas range expansion and restricted dispersal with isolation by distance were proportionally more important in the history of the two deeper-water species. H. trimaculatus has the most widespread haplotypes [average clade distance (D(c)) of nonsingleton haplotypes = 1169 km], indicating potentially high dispersal capabilities, whereas H. barbouri has the least widespread haplotypes (average D(c) = 67 km) indicating potentially lower dispersal capabilities. Pleistocene separation of marine basins and postglacial flooding of the Sunda Shelf are extrinsic factors likely to have contributed to the phylogeographical structure observed, whereas differences among the species appear to reflect their individual ecologies.

Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects

PubMed Central

Smith, Matthew J.; Cobia, Derin J.; Reilly, James L.; Gilman, Jodi; Roberts, Andrea G.; Alpert, Kathryn I.; Wang, Lei; Breiter, Hans C.; Csernansky, John G.

2015-01-01

Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large- deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ- CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM. Shape differences observed in CON-CUD were associated with poorer EM, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD abstinence. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis. PMID:25760303

Different Simultaneous Sleep States in the Hippocampus and Neocortex.

PubMed

Emrick, Joshua J; Gross, Brooks A; Riley, Brett T; Poe, Gina R

2016-12-01

Investigators assign sleep-waking states using brain activity collected from a single site, with the assumption that states occur at the same time throughout the brain. We sought to determine if sleep-waking states differ between two separate structures: the hippocampus and neocortex. We measured electrical signals (electroencephalograms and electromyograms) during sleep from the hippocampus and neocortex of five freely behaving adult male rats. We assigned sleep-waking states in 10-sec epochs based on standard scoring criteria across a 4-h recording, then analyzed and compared states and signals from simultaneous epochs between sites. We found that the total amount of each state, assigned independently using the hippocampal and neocortical signals, was similar between the hippocampus and neocortex. However, states at simultaneous epochs were different as often as they were the same (P = 0.82). Furthermore, we found that the progression of states often flowed through asynchronous state-pairs led by the hippocampus. For example, the hippocampus progressed from transition-to-rapid eye movement sleep to rapid eye movement sleep before the neocortex more often than in synchrony with the neocortex (38.7 ± 16.2% versus 15.8 ± 5.6% mean ± standard error of the mean). We demonstrate that hippocampal and neocortical sleep-waking states often differ in the same epoch. Consequently, electrode location affects estimates of sleep architecture, state transition timing, and perhaps even percentage of time in sleep states. Therefore, under normal conditions, models assuming brain state homogeneity should not be applied to the sleeping or waking brain. © 2016 Associated Professional Sleep Societies, LLC.

Dissociating hippocampal and basal ganglia contributions to category learning using stimulus novelty and subjective judgments

PubMed Central

Seger, Carol A.; Dennison, Christina S.; Lopez-Paniagua, Dan; Peterson, Erik J.; Roark, Aubrey A.

2011-01-01

We identified factors leading to hippocampal and basal ganglia recruitment during categorization learning. Subjects alternated between blocks of a standard trial and error category learning task and a subjective judgment task. In the subjective judgments task subjects categorized the stimulus and then instead of receiving feedback they indicated the basis of their response using 4 options: Remember: Conscious episodic memory of previous trials. Know-Automatic: Automatic, rapid response accompanied by conscious awareness of category membership. Know-Intuition: A “gut feeling” without fully conscious knowledge of category membership. Guess: Guessing. In addition, new stimuli were introduced throughout the experiment to examine effects of novelty. Categorization overall recruited both the basal ganglia and posterior hippocampus. However, basal ganglia activity was found during Know judgments (both Automatic and Intuition), whereas posterior hippocampus activity was found during Remember judgments. Granger causality mapping indicated interactions between the basal ganglia and hippocampus, with the putamen exerting directed influence on the posterior hippocampus, which in turn exerted directed influence on the posterior caudate nucleus. We also found a region of anterior hippocampus that showed decreased activity relative to baseline during categorization overall, and showed a strong novelty effect. Our results indicate that subjective measures may be effective in dissociating basal ganglia from hippocampal dependent learning, and that the basal ganglia are involved in both conscious and unconscious learning. They also indicate a dissociation within the hippocampus, in which the anterior regions are sensitive to novelty, and the posterior regions are involved in memory based categorization learning. PMID:21255655

Electrographic waveform structure predicts laminar focus location in a model of temporal lobe seizures in vitro.

PubMed

Adams, Christopher; Adams, Natalie E; Traub, Roger D; Whittington, Miles A

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is 'victim' or 'perpetrator': The structure is ideally placed to 'broadcast' epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin - a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role.

Electrographic Waveform Structure Predicts Laminar Focus Location in a Model of Temporal Lobe Seizures In Vitro

PubMed Central

Adams, Christopher; Adams, Natalie E.; Traub, Roger D.; Whittington, Miles A.

2015-01-01

Temporal lobe epilepsy is the most common form of partial-onset epilepsy and accounts for the majority of adult epilepsy cases in most countries. A critical role for the hippocampus (and to some extent amygdala) in the pathology of these epilepsies is clear, with selective removal of these regions almost as effective as temporal lobectomy in reducing subsequent seizure risk. However, there is debate about whether hippocampus is ‘victim’ or ‘perpetrator’: The structure is ideally placed to ‘broadcast’ epileptiform activity to a great many other brain regions, but removal often leaves epileptiform events still occurring in cortex, particularly in adjacent areas, and recruitment of the hippocampus into seizure-like activity has been shown to be difficult in clinically-relevant models. Using a very simple model of acute epileptiform activity with known, single primary pathology (GABAA Receptor partial blockade), we track the onset and propagation of epileptiform events in hippocampus, parahippocampal areas and neocortex. In this model the hippocampus acts as a potential seizure focus for the majority of observed events. Events with hippocampal focus were far more readily propagated throughout parahippocampal areas and into neocortex than vice versa. The electrographic signature of events of hippocampal origin was significantly different to those of primary neocortical origin – a consequence of differential laminar activation. These data confirm the critical role of the hippocampus in epileptiform activity generation in the temporal lobe and suggest the morphology of non-invasive electrical recording of neocortical interictal events may be useful in confirming this role. PMID:25799020

DAILY PATTERNS OF CLOCK AND COGNITION-RELATED FACTORS ARE MODIFIED IN THE HIPPOCAMPUS OF VITAMIN A-DEFICIENT RATS

PubMed Central

Golini, Rebeca S.; Delgado, Silvia M.; Navigatore Fonzo, Lorena S.; Ponce, Ivana T.; Lacoste, María G.; Anzulovich, Ana C.

2012-01-01

The circadian expression of clock and clock-controlled cognition-related genes in the hippocampus would be essential to achieve an optimal daily cognitive performance. There is some evidence that retinoid nuclear receptors (RARs and RXRs) can regulate circadian gene expression in different tissues. In this study, Holtzman male rats from control and vitamin A-deficient groups were sacrificed throughout a 24-h period and hippocampus samples were isolated every 4 or 5 h. RARα and RXRβ expression level was quantified and daily expression patterns of clock BMAL1, PER1, RORα and REVERB genes, RORα and REVERB proteins, as well as temporal expression of cognition-related RC3 and BDNF genes were determined in the hippocampus of the two groups of rats. Our results show significant daily variations of BMAL1, PER1, RORα and REVERB genes, RORα and REVERB proteins and, consequently, daily oscillating expression of RC3 and BDNF genes in the rat hippocampus. Vitamin A deficiency reduced RXRβ mRNA level as well as the amplitude of PER1, REVERB gene and REVERB protein rhythms, and phase-shifted the daily peaks of BMAL1 and RORα mRNA, RORα protein and RC3 and BDNF mRNA levels. Thus, nutritional factors, such as vitamin A and its derivatives the retinoids, might modulate daily patterns of BDNF and RC3 expression in the hippocampus and they could be essential to maintain an optimal daily performance at molecular level in this learning-and-memory-related brain area. PMID:22434687

Hippocampus shape analysis and late-life depression.

PubMed

Zhao, Zheen; Taylor, Warren D; Styner, Martin; Steffens, David C; Krishnan, K Ranga R; MacFall, James R

2008-03-19

Major depression in the elderly is associated with brain structural changes and vascular lesions. Changes in the subcortical regions of the limbic system have also been noted. Studies examining hippocampus volumetric differences in depression have shown variable results, possibly due to any volume differences being secondary to local shape changes rather than differences in the overall volume. Shape analysis offers the potential to detect such changes. The present study applied spherical harmonic (SPHARM) shape analysis to the left and right hippocampi of 61 elderly subjects with major depression and 43 non-depressed elderly subjects. Statistical models controlling for age, sex, and total cerebral volume showed a significant reduction in depressed compared with control subjects in the left hippocampus (F(1,103) = 5.26; p = 0.0240) but not right hippocampus volume (F(1,103) = 0.41; p = 0.5213). Shape analysis showed significant differences in the mid-body of the left (but not the right) hippocampus between depressed and controls. When the depressed group was dichotomized into those whose depression was remitted at time of imaging and those who were unremitted, the shape comparison showed remitted subjects to be indistinguishable from controls (both sides) while the unremitted subjects differed in the midbody and the lateral side near the head. Hippocampal volume showed no difference between controls and remitted subjects but nonremitted subjects had significantly smaller left hippocampal volumes with no significant group differences in the right hippocampus. These findings may provide support to other reports of neurogenic effects of antidepressants and their relation to successful treatment for depressive symptoms.

Iron Deficiency with or without Anemia Impairs Prepulse Inhibition of the Startle Reflex

PubMed Central

Pisansky, Marc T.; Wickham, Robert J.; Su, Jianjun; Fretham, Stephanie; Yuan, Li-Lian; Sun, Mu; Gewirtz, Jonathan C.; Georgieff, Michael K.

2013-01-01

Iron deficiency (ID) during early life causes long-lasting detrimental cognitive sequelae, many of which are linked to alterations in hippocampus function, dopamine synthesis, and the modulation of dopaminergic circuitry by the hippocampus. These same features have been implicated in the origins of schizophrenia, a neuropsychiatric disorder with significant cognitive impairments. Deficits in sensorimotor gating represent a reliable endophenotype of schizophrenia that can be measured by prepulse inhibition (PPI) of the acoustic startle reflex. Using two rodent model systems, we investigated the influence of early-life ID on PPI in adulthood. To isolate the role of hippocampal iron in PPI, our mouse model utilized a timed (embryonic day 18.5), hippocampus-specific knockout of Slc11a2, a gene coding an important regulator of cellular iron uptake, the divalent metal transport type 1 protein (DMT-1). Our second model used a classic rat dietary-based global ID during gestation, a condition that closely mimics human gestational ID anemia (IDA). Both models exhibited impaired PPI in adulthood. Furthermore, our DMT-1 knockout model displayed reduced long-term potentiation (LTP) and elevated paired pulse facilitation (PPF), electrophysiological results consistent with previous findings in the IDA rat model. These results, in combination with previous findings demonstrating impaired hippocampus functioning and altered dopaminergic and glutamatergic neurotransmission, suggest that iron availability within the hippocampus is critical for the neurodevelopmental processes underlying sensorimotor gating. Ultimately, evidence of reduced PPI in both of our models may offer insights into the roles of fetal ID and the hippocampus in the pathophysiology of schizophrenia. PMID:23733517

Combining Theory, Model, and Experiment to Explain How Intrinsic Theta Rhythms Are Generated in an In Vitro Whole Hippocampus Preparation without Oscillatory Inputs

PubMed Central

Ferguson, Katie A.

2017-01-01

Abstract Scientists have observed local field potential theta rhythms (3–12 Hz) in the hippocampus for decades, but understanding the mechanisms underlying their generation is complicated by their diversity in pharmacological and frequency profiles. In addition, interactions with other brain structures and oscillatory drives to the hippocampus during distinct brain states has made it difficult to identify hippocampus-specific properties directly involved in theta generation. To overcome this, we develop cellular-based network models using a whole hippocampus in vitro preparation that spontaneously generates theta rhythms. Building on theoretical and computational analyses, we find that spike frequency adaptation and postinhibitory rebound constitute a basis for theta generation in large, minimally connected CA1 pyramidal (PYR) cell network models with fast-firing parvalbumin-positive (PV+) inhibitory cells. Sparse firing of PYR cells and large excitatory currents onto PV+ cells are present as in experiments. The particular theta frequency is more controlled by PYR-to-PV+ cell interactions rather than PV+-to-PYR cell interactions. We identify two scenarios by which theta rhythms can emerge, and they can be differentiated by the ratio of excitatory to inhibitory currents to PV+ cells, but not to PYR cells. Only one of the scenarios is consistent with data from the whole hippocampus preparation, which leads to the prediction that the connection probability from PV+ to PYR cells needs to be larger than from PYR to PV+ cells. Our models can serve as a platform on which to build and develop an understanding of in vivo theta generation. PMID:28791333

COMPENSATORY CHANGES IN THE HIPPOCAMPUS FOLLOWING INTRADENTATE INFUSION OF COLCHICINE

EPA Science Inventory

Direct infusion of colchicine into the dentate gyrus of the hippocampus kills granule cells and elicits compensatory behavioral, neurochemical and neuroanatomical changes. olchicine-treated rats are less sensitive to the behavioral effects of cholinergic muscarinic receptor antag...

Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

PubMed Central

Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

2016-01-01

Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and IL-10 levels in serum. Infliximab also prevents neuroinflammation, reduces microglial activation, translocates NF-kB into nucleoli and normalizes TNF-a and IL-1b content in hippocampus. This was associated with normalization of AMPA receptors membrane expression in hippocampus and of spatial learning and memory. The results suggest that peripheral inflammation contributes to spatial learning impairment in PCS rats. Treatment with anti-TNF-a could be a new therapeutic approach to improve cognitive function in patients with HE. PMID:27853420

DEVELOPMENTAL HYPOTHYROIDISM ALTERS SYNAPTIC TRANSMISSION IN DENTATE GYRUS AND AREA CA1 OF HIPPOCAMPUS.

EPA Science Inventory

Hypothyroidism during critical periods of brain developmental leads to learning deficits and alterations in hippocampal structure. Neurophysiological properties of the hippocampus, however, have not been well characterized. The present study examined field potentials evoked in...

Anterior hippocampus: the anatomy of perception, imagination and episodic memory

PubMed Central

Zeidman, Peter; Maguire, Eleanor A.

2017-01-01

The brain creates a model of the world around us. We can use this representation to perceive and comprehend what we see at any given moment, but also to vividly re-experience scenes from our past and imagine future (or even fanciful) scenarios. Recent work has shown that these cognitive functions — perception, imagination and recall of scenes and events — all engage the anterior hippocampus. Here we capitalise on new findings from functional neuroimaging to propose a model that links high-level cognitive functions to specific structures within the anterior hippocampus. PMID:26865022

Double Dissociation of Conditioning and Declarative Knowledge Relative to the Amygdala and Hippocampus in Humans

NASA Astrophysics Data System (ADS)

Bechara, Antoine; Tranel, Daniel; Damasio, Hanna; Adolphs, Ralph; Rockland, Charles; Damasio, Antonio R.

1995-08-01

A patient with selective bilateral damage to the amygdala did not acquire conditioned autonomic responses to visual or auditory stimuli but did acquire the declarative facts about which visual or auditory stimuli were paired with the unconditioned stimulus. By contrast, a patient with selective bilateral damage to the hippocampus failed to acquire the facts but did acquire the conditioning. Finally, a patient with bilateral damage to both amygdala and hippocampal formation acquired neither the conditioning nor the facts. These findings demonstrate a double dissociation of conditioning and declarative knowledge relative to the human amygdala and hippocampus.

Fish, fans and hydroids: host species of pygmy seahorses.

PubMed

Reijnen, Bastian T; van der Meij, Sancia E T; van Ofwegen, Leen P

2011-01-01

An overview of the octocoral and hydrozoan host species of pygmy seahorses is provided based on literature records and recently collected field data for Hippocampus bargibanti, Hippocampus denise and Hippocampus pontohi. Seven new associations are recognized and an overview of the so far documented host species is given. A detailed re-examination of octocoral type material and a review of the taxonomic history of the alcyonacean genera Annella (Subergorgiidae) and Muricella (Acanthogorgiidae) are included as baseline for future revisions. The host specificity and colour morphs of pygmy seahorses are discussed, as well as the reliability of (previous) identifications and conservation issues.

Reduced hippocampal functional connectivity in Alzheimer disease.

PubMed

Allen, Greg; Barnard, Holly; McColl, Roderick; Hester, Andrea L; Fields, Julie A; Weiner, Myron F; Ringe, Wendy K; Lipton, Anne M; Brooker, Matthew; McDonald, Elizabeth; Rubin, Craig D; Cullum, C Munro

2007-10-01

To determine if functional connectivity of the hippocampus is reduced in patients with Alzheimer disease. Functional connectivity magnetic resonance imaging was used to investigate coherence in the magnetic resonance signal between the hippocampus and all other regions of the brain. Eight patients with probable Alzheimer disease and 8 healthy volunteers. Control subjects showed hippocampal functional connectivity with diffuse cortical, subcortical, and cerebellar sites, while patients demonstrated markedly reduced functional connectivity, including an absence of connectivity with the frontal lobes. These findings suggest a functional disconnection between the hippocampus and other brain regions in patients with Alzheimer disease.

Manual morphometry of hippocampus and amygdala in adults with attention-deficit hyperactivity disorder.

PubMed

Nickel, Kathrin; Tebartz van Elst, Ludger; Perlov, Evgeniy; Jitten-Schachenmeier, Renate; Beier, Daniel; Endres, Dominique; Goll, Peter; Philipsen, Alexandra; Maier, Simon

2017-09-30

Previous studies have pointed to the involvement of limbic structures in the genesis of attention deficit hyperactivity disorder (ADHD). The present researchers manually segmented magnetic resonance images of 30 individuals with ADHD and 30 individually matched controls, focusing on amygdala and hippocampus volumes. Neither hippocampus nor amygdala volume differed significantly between individuals with and without ADHD. However, ADHD patients with higher hyperactivity scores had significantly smaller left amygdala volumes. This finding suggests that limbic alterations are significant in hyperactive symptoms in the pathophysiology of ADHD. Copyright © 2017. Published by Elsevier B.V.

High-throughput, fully-automated volumetry for prediction of MMSE and CDR decline in mild cognitive impairment

PubMed Central

Kovacevic, Sanja; Rafii, Michael S.; Brewer, James B.

2008-01-01

Medial temporal lobe (MTL) atrophy is associated with increased risk for conversion to Alzheimer's disease (AD), but manual tracing techniques and even semi-automated techniques for volumetric assessment are not practical in the clinical setting. In addition, most studies that examined MTL atrophy in AD have focused only on the hippocampus. It is unknown the extent to which volumes of amygdala and temporal horn of the lateral ventricle predict subsequent clinical decline. This study examined whether measures of hippocampus, amygdala, and temporal horn volume predict clinical decline over the following 6-month period in patients with mild cognitive impairment (MCI). Fully-automated volume measurements were performed in 269 MCI patients. Baseline volumes of the hippocampus, amygdala, and temporal horn were evaluated as predictors of change in Mini-mental State Exam (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR SB) over a 6-month interval. Fully-automated measurements of baseline hippocampus and amygdala volumes correlated with baseline delayed recall scores. Patients with smaller baseline volumes of the hippocampus and amygdala or larger baseline volumes of the temporal horn had more rapid subsequent clinical decline on MMSE and CDR SB. Fully-automated and rapid measurement of segmental MTL volumes may help clinicians predict clinical decline in MCI patients. PMID:19474571

The Hippocampus Supports High-Resolution Binding in the Service of Perception, Working Memory and Long-Term Memory

PubMed Central

Yonelinas, Andrew P.

2013-01-01

It is well established that the hippocampus plays a critical role in our ability to recollect past events. A number of recent studies have indicated that the hippocampus may also play a critical role in working memory and perception, but these results have been highly controversial because other similar studies have failed to find evidence for hippocampal involvement. Thus, the precise role that the hippocampus plays in cognition is still debated. In the current paper, I propose that the hippocampus supports the generation and utilization of complex high-resolution bindings that link together the qualitative aspects that make up an event; these bindings are essential for recollection, and they can also contribute to performance across a variety of tasks including perception and working memory. An examination of the existing patient literature provides support for this proposal by showing that hippocampal damage leads to impairments on perception and working memory tasks that require complex high-resolution bindings. Conversely, hippocampal damage is much less likely to lead to impairments on tasks that require only low-resolution or simple associations/relations. The current proposal can be distinguished from earlier accounts of hippocampal function, and it generates a number of novel predictions that can be tested in future studies. PMID:23721964

Influence of different estrogens on neuroplasticity and cognition in the hippocampus.

PubMed

Barha, Cindy K; Galea, Liisa A M

2010-10-01

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain. This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats. Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning. Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females. Copyright © 2010 Elsevier B.V. All rights reserved.

Female hatchling American kestrels have a larger hippocampus than males: A link with sexual size dimorphism?

USGS Publications Warehouse

Guigueno, Melanie F.; Karouna-Renier, Natalie K.; Henry, Paula F. P.; Head, Jessica A.; Peters, Lisa E.; Palace, Vince P.; Letcher, Robert J.; Fernie, Kimberly J.

2018-01-01

The brain and underlying cognition may vary adaptively according to an organism’s ecology. As with all raptor species, adult American kestrels (Falco sparverius) are sexually dimorphic with females being larger than males. Related to this sexual dimorphism, kestrels display sex differences in hunting and migration, with females ranging more widely than males, suggesting possible sex differences in spatial cognition. However, hippocampus volume, the brain region responsible for spatial cognition, has not been investigated in raptors. Here, we measured hippocampus and telencephalon volumes in American kestrel hatchlings. Female hatchlings had a significantly larger hippocampus relative to the telencephalon and brain weight than males (∼12% larger), although telencephalon volume relative to brain weight and body size was similar between the sexes. The magnitude of this hippocampal sex difference is similar to that reported between male and female polygynous Microtus voles and migratory and non-migratory subspecies of Zonotrichia sparrows. Future research should determine if this sex difference in relative hippocampus volume of hatchling kestrels persists into adulthood and if similar patterns exist in other raptor species, thus potentially linking sex differences in the brain to sex differences of space use of adults in the wild.

Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

NASA Astrophysics Data System (ADS)

Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

2004-03-01

Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

What relates newspaper, definite, and clothing? An article describing deficits in convergent problem solving and creativity following hippocampal damage

PubMed Central

Warren, David E.; Kurczek, Jake; Duff, Melissa C.

2016-01-01

Creativity relies on a diverse set of cognitive processes associated with distinct neural correlates, and one important aspect of creativity, divergent thinking, has been associated with the hippocampus. However, hippocampal contributions to another important aspect of creativity, convergent problem solving, have not been investigated. We tested the necessity of hippocampus for convergent problem solving using a neuropsychological method. Participants with amnesia due to hippocampal damage (N=5) and healthy normal comparison participants (N=5) were tested using a task that promoted solutions based on existing knowledge (Bowden and Jung-Beeman, 2003). During each trial, participants were given a list of three words (e.g., fly, man, place) and asked to respond with a word that could be combined with each of the three words (e.g., fire). The amnesic group produced significantly fewer correct responses than the healthy comparison group. These findings indicate that the hippocampus is necessary for normal convergent problem solving and that changes in the status of the hippocampus should affect convergent problem solving in the context of creative problem-solving across short intervals. This proposed contribution of the hippocampus to convergent problem solving is consistent with an expanded perspective on hippocampal function that acknowledges its role in cognitive processes beyond declarative memory. PMID:27010751

Parallel and convergent processing in grid cell, head-direction cell, boundary cell, and place cell networks

PubMed Central

Brandon, Mark P; Koenig, Julie; Leutgeb, Stefan

2014-01-01

The brain is able to construct internal representations that correspond to external spatial coordinates. Such brain maps of the external spatial topography may support a number of cognitive functions, including navigation and memory. The neuronal building block of brain maps are place cells, which are found throughout the hippocampus of rodents and, in a lower proportion, primates. Place cells typically fire in one or few restricted areas of space, and each area where a cell fires can range, along the dorsoventral axis of the hippocampus, from 30 cm to at least several meters. The sensory processing streams that give rise to hippocampal place cells are not fully understood, but substantial progress has been made in characterizing the entorhinal cortex, which is the gateway between neocortical areas and the hippocampus. Entorhinal neurons have diverse spatial firing characteristics, and the different entorhinal cell types converge in the hippocampus to give rise to a single, spatially modulated cell type—the place cell. We therefore suggest that parallel information processing in different classes of cells—as is typically observed at lower levels of sensory processing—continues up into higher level association cortices, including those that provide the inputs to hippocampus. WIREs Cogn Sci 2014, 5:207–219. doi: 10.1002/wcs.1272 PMID:24587849

iTRAQ proteomic analysis of the hippocampus in a rat model of nicotine-induced conditioned place preference.

PubMed

Zhu, Beibei; Li, Xiangyu; Chen, Huan; Wang, Hongjuan; Zhu, Xinchao; Hou, Hongwei; Hu, Qingyuan

2017-05-13

Repeated exposures to nicotine are known to result in persistent changes in proteins expression in addiction-related brain regions, such as the striatum, nucleus accumbens and prefrontal cortex, but the changes induced in the protein content of the hippocampus remain poorly studied. This study established a rat model of nicotine-induced conditioned place preference (CPP), and screened for proteins that were differentially expressed in the hippocampus of these rats using isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The nicotine-induced CPP was established by subcutaneously injecting rats with 0.2 mg/kg nicotine. Relative to the control (saline) group, the nicotine group showed 0.67- and 1.5-fold changes in 117 and 10 hippocampal proteins, respectively. These differentially expressed proteins are mainly involved in calcium-mediated signaling, neurotransmitter transport, GABAergic synapse function, long-term synaptic potentiation and nervous system development. Furthermore, RT-PCR was used to confirmed the results of the proteomic analysis. Our findings identify several proteins and cellular signaling pathways potentially involved in the molecular mechanisms in the hippocampus that underlie nicotine addiction. These results provide insights into the mechanisms of nicotine treatment in hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

Decoding individual episodic memory traces in the human hippocampus.

PubMed

Chadwick, Martin J; Hassabis, Demis; Weiskopf, Nikolaus; Maguire, Eleanor A

2010-03-23

In recent years, multivariate pattern analyses have been performed on functional magnetic resonance imaging (fMRI) data, permitting prediction of mental states from local patterns of blood oxygen-level-dependent (BOLD) signal across voxels. We previously demonstrated that it is possible to predict the position of individuals in a virtual-reality environment from the pattern of activity across voxels in the hippocampus. Although this shows that spatial memories can be decoded, substantially more challenging, and arguably only possible to investigate in humans, is whether it is feasible to predict which complex everyday experience, or episodic memory, a person is recalling. Here we document for the first time that traces of individual rich episodic memories are detectable and distinguishable solely from the pattern of fMRI BOLD signals across voxels in the human hippocampus. In so doing, we uncovered a possible functional topography in the hippocampus, with preferential episodic processing by some hippocampal regions over others. Moreover, our results imply that the neuronal traces of episodic memories are stable (and thus predictable) even over many re-activations. Finally, our data provide further evidence for functional differentiation within the medial temporal lobe, in that we show the hippocampus contains significantly more episodic information than adjacent structures. 2010 Elsevier Ltd. All rights reserved.

Prolactin Stimulates Precursor Cells in the Adult Mouse Hippocampus

PubMed Central

Walker, Tara L.; Vukovic, Jana; Koudijs, Margaretha M.; Blackmore, Daniel G.; Mackay, Eirinn W.; Sykes, Alex M.; Overall, Rupert W.; Hamlin, Adam S.; Bartlett, Perry F.

2012-01-01

In the search for ways to combat degenerative neurological disorders, neurogenesis-stimulating factors are proving to be a promising area of research. In this study, we show that the hormonal factor prolactin (PRL) can activate a pool of latent precursor cells in the adult mouse hippocampus. Using an in vitro neurosphere assay, we found that the addition of exogenous PRL to primary adult hippocampal cells resulted in an approximate 50% increase in neurosphere number. In addition, direct infusion of PRL into the adult dentate gyrus also resulted in a significant increase in neurosphere number. Together these data indicate that exogenous PRL can increase hippocampal precursor numbers both in vitro and in vivo. Conversely, PRL null mice showed a significant reduction (approximately 80%) in the number of hippocampal-derived neurospheres. Interestingly, no deficit in precursor proliferation was observed in vivo, indicating that in this situation other niche factors can compensate for a loss in PRL. The PRL loss resulted in learning and memory deficits in the PRL null mice, as indicated by significant deficits in the standard behavioral tests requiring input from the hippocampus. This behavioral deficit was rescued by direct infusion of recombinant PRL into the hippocampus, indicating that a lack of PRL in the adult mouse hippocampus can be correlated with impaired learning and memory. PMID:22973440

Playing Super Mario 64 increases hippocampal grey matter in older adults.

PubMed

West, Greg L; Zendel, Benjamin Rich; Konishi, Kyoko; Benady-Chorney, Jessica; Bohbot, Veronique D; Peretz, Isabelle; Belleville, Sylvie

2017-01-01

Maintaining grey matter within the hippocampus is important for healthy cognition. Playing 3D-platform video games has previously been shown to promote grey matter in the hippocampus in younger adults. In the current study, we tested the impact of 3D-platform video game training (i.e., Super Mario 64) on grey matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex (DLPFC) of older adults. Older adults who were 55 to 75 years of age were randomized into three groups. The video game experimental group (VID; n = 8) engaged in a 3D-platform video game training over a period of 6 months. Additionally, an active control group took a series of self-directed, computerized music (piano) lessons (MUS; n = 12), while a no-contact control group did not engage in any intervention (CON; n = 13). After training, a within-subject increase in grey matter within the hippocampus was significant only in the VID training group, replicating results observed in younger adults. Active control MUS training did, however, lead to a within-subject increase in the DLPFC, while both the VID and MUS training produced growth in the cerebellum. In contrast, the CON group displayed significant grey matter loss in the hippocampus, cerebellum and the DLPFC.

Cooperative interactions between hippocampal and striatal systems support flexible navigation

PubMed Central

Brown, Thackery I; Ross, Robert S; Tobyne, Sean M; Stern, Chantal E

2012-01-01

Research in animals and humans has demonstrated that the hippocampus is critical for retrieving distinct representations of overlapping sequences of information. There is recent evidence that the caudate nucleus and orbitofrontal cortex are also involved in disambiguation of overlapping spatial representations. The hippocampus and caudate are functionally distinct regions, but both have anatomical links with the orbitofrontal cortex. The present study used an fMRI-based functional connectivity analysis in humans to examine the functional relationship between the hippocampus, caudate, and orbitofrontal cortex when participants use contextual information to navigate well-learned spatial routes which share common elements. Participants were trained outside the scanner to navigate virtual mazes from a first-person perspective. Overlapping condition mazes began and ended at distinct locations, but converged in the middle to share some hallways with another maze. Non-overlapping condition mazes did not share any hallways with any other maze. Successful navigation through the overlapping hallways required contextual information identifying the current navigational route to guide the appropriate response for a given trial. Results revealed greater functional connectivity between the hippocampus, caudate, and orbitofrontal cortex for overlapping mazes compared to non-overlapping mazes. The current findings suggest that the hippocampus and caudate interact with prefrontal structures cooperatively for successful contextually-dependent navigation. PMID:22266411

Hippocampus and amygdala morphology in adults with attention-deficit hyperactivity disorder

PubMed Central

Perlov, Evgeniy; Philipsen, Alexandra; Tebartz van Elst, Ludger; Ebert, Dieter; Henning, Juergen; Maier, Simon; Bubl, Emanuel; Hesslinger, Bernd

2008-01-01

Objective Attention-deficit hyperactivity disorder (ADHD) in adulthood is a serious health problem with a prevalence of up to 4%. Limbic structures have been implicated in the genesis of ADHD; it has been suggested that they mediate mood and cognitive disturbances in affected individuals. Recently, a large study involving children and adolescents with ADHD reported bilateral enlargement of the hippocampus and indirect evidence of amygdala volume loss in this patient sample. We sought to test the hypothesis that, like in pediatric patients, there might be hippocampus and amygdala volume abnormalities in adult patients with ADHD. Methods We studied 27 adult patients with ADHD and 27 group-matched healthy volunteers using a 1.5 T magnetic resonance imaging scanner. We manually obtained morphometric measurements of the regions mentioned. Results In contrast to previous findings in children and adolescents, we found no significant differences in hippocampus and amygdala volumes among adults with and without the disorder. Conclusion Findings of hippocampus enlargement and amygdala volume loss are not very stable across different samples of patients with ADHD. Contradictory findings may be related to the different locations of alterations along the complex circuits responsible for the different symptoms of ADHD. Further studies involving larger samples of adult patients with ADHD and using multimodal designs are needed. PMID:18982173

Involvement of Thalamus in Initiation of Epileptic Seizures Induced by Pilocarpine in Mice

PubMed Central

Li, Yong-Hua; Li, Jia-Jia; Lu, Qin-Chi; Gong, Hai-Qing; Liang, Pei-Ji

2014-01-01

Studies have suggested that thalamus is involved in temporal lobe epilepsy, but the role of thalamus is still unclear. We obtained local filed potentials (LFPs) and single-unit activities from CA1 of hippocampus and parafascicular nucleus of thalamus during the development of epileptic seizures induced by pilocarpine in mice. Two measures, redundancy and directionality index, were used to analyze the electrophysiological characters of neuronal activities and the information flow between thalamus and hippocampus. We found that LFPs became more regular during the seizure in both hippocampus and thalamus, and in some cases LFPs showed a transient disorder at seizure onset. The variation tendency of the peak values of cross-correlation function between neurons matched the variation tendency of the redundancy of LFPs. The information tended to flow from thalamus to hippocampus during seizure initiation period no matter what the information flow direction was before the seizure. In some cases the information flow was symmetrically bidirectional, but none was found in which the information flowed from hippocampus to thalamus during the seizure initiation period. In addition, inactivation of thalamus by tetrodotoxin (TTX) resulted in a suppression of seizures. These results suggest that thalamus may play an important role in the initiation of epileptic seizures. PMID:24778885

UV irradiation to mouse skin decreases hippocampal neurogenesis and synaptic protein expression via HPA axis activation.

PubMed

Han, Mira; Ban, Jae-Jun; Bae, Jung-Soo; Shin, Chang-Yup; Lee, Dong Hun; Chung, Jin Ho

2017-11-14

The skin senses external environment, including ultraviolet light (UV). Hippocampus is a brain region that is responsible for memory and emotion. However, changes in hippocampus by UV irradiation to the skin have not been studied. In this study, after 2 weeks of UV irradiation to the mouse skin, we examined molecular changes related to cognitive functions in the hippocampus and activation of the hypothalamic-pituitary-adrenal (HPA) axis. UV exposure to the skin decreased doublecortin-positive immature neurons and synaptic proteins, including N-methyl-D-aspartate receptor 2 A and postsynaptic density protein-95, in the hippocampus. Moreover, we observed that UV irradiation to the skin down-regulated brain-derived neurotrophic factor expression and ERK signaling in the hippocampus, which are known to modulate neurogenesis and synaptic plasticity. The cutaneous and central HPA axes were activated by UV, which resulted in significant increases in serum levels of corticosterone. Subsequently, UV irradiation to the skin activated the glucocorticoid-signaling pathway in the hippocampal dentate gyrus. Interestingly, after 6 weeks of UV irradiation, mice showed depression-like behavior in the tail suspension test. Taken together, our data suggest that repeated UV exposure through the skin may negatively affect hippocampal neurogenesis and synaptic plasticity along with HPA axis activation.

Modifiable factors that alter the size of the hippocampus with ageing.

PubMed

Fotuhi, Majid; Do, David; Jack, Clifford

2012-03-13

The hippocampus is particularly vulnerable to the neurotoxic effects of obesity, diabetes mellitus, hypertension, hypoxic brain injury, obstructive sleep apnoea, bipolar disorder, clinical depression and head trauma. Patients with these conditions often have smaller hippocampi and experience a greater degree of cognitive decline than individuals without these comorbidities. Moreover, hippocampal atrophy is an established indicator for conversion from the normal ageing process to developing mild cognitive impairment and dementia. As such, an important aim is to ascertain which modifiable factors can have a positive effect on the size of the hippocampus throughout life. Observational studies and preliminary clinical trials have raised the possibility that physical exercise, cognitive stimulation and treatment of general medical conditions can reverse age-related atrophy in the hippocampus, or even expand its size. An emerging concept--the dynamic polygon hypothesis--suggests that treatment of modifiable risk factors can increase the volume or prevent atrophy of the hippocampus. According to this hypothesis, a multidisciplinary approach, which involves strategies to both reduce neurotoxicity and increase neurogenesis, is likely to be successful in delaying the onset of cognitive impairment with ageing. Further research on the constellation of interventions that could be most effective is needed before recommendations can be made for implementing preventive and therapeutic strategies.

Deficits in hippocampus-mediated Pavlovian conditioning in endogenous hypercortisolism.

PubMed

Grillon, Christian; Smith, Kathryn; Haynos, Ann; Nieman, Lynnette K

2004-12-01

Elevated endogenous levels of corticosteroids cause neural dysfunction and loss, especially within the hippocampus, as well as cognitive impairment in hippocampus-mediated tasks. Because Cushing's syndrome patients suffer from hypercortisolism, they represent a unique opportunity to study the impact of elevated glucocorticoids on cognitive functions. The aim of this study was to examine the performance of Cushing's syndrome patients on trace eyeblink conditioning, a cross-species, hippocampal-mediated test of learning and memory. Eleven Cushing's syndrome patients and 11 healthy control subjects participated in an eyeblink trace conditioning test (1000-msec trace) and a task of declarative memory for words. Salivary cortisol was collected in both the patients and the control subjects, and urinary free cortisol was collected in the patients only. The patients exhibited fewer conditional responses and remembered fewer words, compared with the control subjects. Cortisol levels correlated with immediate and delayed declarative memory only. Conditional response correlated with delayed recall after controlling for the magnitude of unconditional response. The integrity of the hippocampus seems to be compromised in Cushing's syndrome patients. Trace eyeblink conditioning might be useful both as a clinical tool to examine changes in hippocampus function in Cushing's disease patients and as a translational tool of research on the impact of chronic exposure of glucocorticoids.

Computer-aided classification of Alzheimer's disease based on support vector machine with combination of cerebral image features in MRI

NASA Astrophysics Data System (ADS)

Jongkreangkrai, C.; Vichianin, Y.; Tocharoenchai, C.; Arimura, H.; Alzheimer's Disease Neuroimaging Initiative

2016-03-01

Several studies have differentiated Alzheimer's disease (AD) using cerebral image features derived from MR brain images. In this study, we were interested in combining hippocampus and amygdala volumes and entorhinal cortex thickness to improve the performance of AD differentiation. Thus, our objective was to investigate the useful features obtained from MRI for classification of AD patients using support vector machine (SVM). T1-weighted MR brain images of 100 AD patients and 100 normal subjects were processed using FreeSurfer software to measure hippocampus and amygdala volumes and entorhinal cortex thicknesses in both brain hemispheres. Relative volumes of hippocampus and amygdala were calculated to correct variation in individual head size. SVM was employed with five combinations of features (H: hippocampus relative volumes, A: amygdala relative volumes, E: entorhinal cortex thicknesses, HA: hippocampus and amygdala relative volumes and ALL: all features). Receiver operating characteristic (ROC) analysis was used to evaluate the method. AUC values of five combinations were 0.8575 (H), 0.8374 (A), 0.8422 (E), 0.8631 (HA) and 0.8906 (ALL). Although “ALL” provided the highest AUC, there were no statistically significant differences among them except for “A” feature. Our results showed that all suggested features may be feasible for computer-aided classification of AD patients.

Playing Super Mario 64 increases hippocampal grey matter in older adults

PubMed Central

Konishi, Kyoko; Benady-Chorney, Jessica; Bohbot, Veronique D.; Peretz, Isabelle; Belleville, Sylvie

2017-01-01

Maintaining grey matter within the hippocampus is important for healthy cognition. Playing 3D-platform video games has previously been shown to promote grey matter in the hippocampus in younger adults. In the current study, we tested the impact of 3D-platform video game training (i.e., Super Mario 64) on grey matter in the hippocampus, cerebellum, and the dorsolateral prefrontal cortex (DLPFC) of older adults. Older adults who were 55 to 75 years of age were randomized into three groups. The video game experimental group (VID; n = 8) engaged in a 3D-platform video game training over a period of 6 months. Additionally, an active control group took a series of self-directed, computerized music (piano) lessons (MUS; n = 12), while a no-contact control group did not engage in any intervention (CON; n = 13). After training, a within-subject increase in grey matter within the hippocampus was significant only in the VID training group, replicating results observed in younger adults. Active control MUS training did, however, lead to a within-subject increase in the DLPFC, while both the VID and MUS training produced growth in the cerebellum. In contrast, the CON group displayed significant grey matter loss in the hippocampus, cerebellum and the DLPFC. PMID:29211727

The Effect of Diabetes Mellitus on Apoptosis in Hippocampus: Cellular and Molecular Aspects.

PubMed

Sadeghi, Akram; Hami, Javad; Razavi, Shahnaz; Esfandiary, Ebrahim; Hejazi, Zahra

2016-01-01

Diabetes mellitus is associated with cognitive deficits in humans and animals. These deficits are paralleled by neurophysiological and structural changes in brain. In diabetic animals, impairments of spatial learning, memory, and cognition occur in association with distinct changes in hippocampus, a key brain area for many forms of learning and memory and are particularly sensitive to changes in glucose homeostasis. However, the multifactorial pathogenesis of diabetic encephalopathy is not yet completely understood. Apoptosis plays a crucial role in diabetes-induce neuronal loss in hippocampus. The effects of diabetes on hippocampus and cognitive/behavioral dysfunctions in experimental models of diabetes are reviewed, with a focus on the negative impact on increased neuronal apoptosis and related cellular and molecular mechanisms. Of all articles that were assessed, most of the experimental studies clearly showed that diabetes causes neuronal apoptosis in hippocampus through multiple mechanisms, including oxidative stress, inhibition of caspases, disturbance in expression of apoptosis regulator genes, as well as deficits in mitochondrial function. The balance between pro-apoptotic and anti-apoptotic signaling may determine the neuronal apoptotic outcome in vitro and in vivo models of experimental diabetes. Dissecting out the mechanisms responsible for diabetes-related changes in the hippocampal cell apoptosis helps improve treatment of impaired cognitive and memory functions in diabetic individuals.

Treatment with tianeptine induces antidepressive-like effects and alters the neurotrophin levels, mitochondrial respiratory chain and cycle Krebs enzymes in the brain of maternally deprived adult rats.

PubMed

Della, Franciela P; Abelaira, Helena M; Réus, Gislaine Z; Santos, Maria Augusta B dos; Tomaz, Débora B; Antunes, Altamir R; Scaini, Giselli; Morais, Meline O S; Streck, Emilio L; Quevedo, João

2013-03-01

Maternally deprived rats were treated with tianeptine (15 mg/kg) once a day for 14 days during their adult phase. Their behavior was then assessed using the forced swimming and open field tests. The BDNF, NGF and energy metabolism were assessed in the rat brain. Deprived rats increased the immobility time, but tianeptine reversed this effect and increased the swimming time; the BDNF levels were decreased in the amygdala of the deprived rats treated with saline and the BDNF levels were decreased in the nucleus accumbens within all groups; the NGF was found to have decreased in the hippocampus, amygdala and nucleus accumbens of the deprived rats; citrate synthase was increased in the hippocampus of non-deprived rats treated with tianeptine and the creatine kinase was decreased in the hippocampus and amygdala of the deprived rats; the mitochondrial complex I and II-III were inhibited, and tianeptine increased the mitochondrial complex II and IV in the hippocampus of the non-deprived rats; the succinate dehydrogenase was increased in the hippocampus of non-deprived rats treated with tianeptine. So, tianeptine showed antidepressant effects conducted on maternally deprived rats, and this can be attributed to its action on the neurochemical pathways related to depression.

Texture analysis of high-resolution FLAIR images for TLE

NASA Astrophysics Data System (ADS)

Jafari-Khouzani, Kourosh; Soltanian-Zadeh, Hamid; Elisevich, Kost

2005-04-01

This paper presents a study of the texture information of high-resolution FLAIR images of the brain with the aim of determining the abnormality and consequently the candidacy of the hippocampus for temporal lobe epilepsy (TLE) surgery. Intensity and volume features of the hippocampus from FLAIR images of the brain have been previously shown to be useful in detecting the abnormal hippocampus in TLE. However, the small size of the hippocampus may limit the texture information. High-resolution FLAIR images show more details of the abnormal intensity variations of the hippocampi and therefore are more suitable for texture analysis. We study and compare the low and high-resolution FLAIR images of six epileptic patients. The hippocampi are segmented manually by an expert from T1-weighted MR images. Then the segmented regions are mapped on the corresponding FLAIR images for texture analysis. The 2-D wavelet transforms of the hippocampi are employed for feature extraction. We compare the ability of the texture features from regular and high-resolution FLAIR images to distinguish normal and abnormal hippocampi. Intracranial EEG results as well as surgery outcome are used as gold standard. The results show that the intensity variations of the hippocampus are related to the abnormalities in the TLE.

[Intervention effects of Jiaotai pills on PCPA-induced insomnia in rats].

PubMed

Yue, He; Zhou, Xiang-Yu; Li, Chun-Yuan; Zou, Zhong-Jie; Wang, Shu-Mei; Liang, Sheng-Wang; Gong, Meng-Juan

2016-09-01

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline. Copyright© by the Chinese Pharmaceutical Association.

Accessing Real-Life Episodic Information from Minutes versus Hours Earlier Modulates Hippocampal and High-Order Cortical Dynamics

PubMed Central

Chen, J.; Honey, C. J.; Simony, E.; Arcaro, M. J.; Norman, K. A.; Hasson, U.

2016-01-01

It is well known that formation of new episodic memories depends on hippocampus, but in real-life settings (e.g., conversation), hippocampal amnesics can utilize information from several minutes earlier. What neural systems outside hippocampus might support this minutes-long retention? In this study, subjects viewed an audiovisual movie continuously for 25 min; another group viewed the movie in 2 parts separated by a 1-day delay. Understanding Part 2 depended on retrieving information from Part 1, and thus hippocampus was required in the day-delay condition. But is hippocampus equally recruited to access the same information from minutes earlier? We show that accessing memories from a few minutes prior elicited less interaction between hippocampus and default mode network (DMN) cortical regions than accessing day-old memories of identical events, suggesting that recent information was available with less reliance on hippocampal retrieval. Moreover, the 2 groups evinced reliable but distinct DMN activity timecourses, reflecting differences in information carried in these regions when Part 1 was recent versus distant. The timecourses converged after 4 min, suggesting a time frame over which the continuous-viewing group may have relied less on hippocampal retrieval. We propose that cortical default mode regions can intrinsically retain real-life episodic information for several minutes. PMID:26240179

Post-stress facilitation of serotonergic, but not noradrenergic, neurotransmission in the dorsal hippocampus prevents learned helplessness development in rats.

PubMed

Joca, Sâmia Regiane Lourenço; Zanelati, Tatiane; Guimarães, Francisco Silveira

2006-05-04

Recent pieces of evidence suggest that the dorsal hippocampus may mediate adaptation to severe and inescapable stress, possibly by the facilitation of serotonergic and/or noradrenergic neurotransmission. Chronic social stress and high corticosteroid levels would impair this coping mechanism, predisposing animals to learned helplessness. To test the hypothesis that increasing serotonin or noradrenaline levels in the dorsal hippocampus would attenuate the development of learned helplessness (LH), rats received inescapable foot shock (IS) and were tested in a shuttle box 24 h latter. Prestressed animals showed impairment of escape responses. This effect was prevented by bilateral intrahippocampal injections of zimelidine (100 nmol/0.5 microl), a serotonin reuptake blocker, immediately after IS. This effect was not observed when zimelidine was administered before or 2 h after IS. Bilateral intrahippocampal injections of desipramine (3 or 30 nmol/0.5 microl), a noradrenaline reuptake blocker, before IS or immediately after it did not prevent LH development. Desipramine (30 nmol) enhanced LH development when injected before IS. These data suggest that poststress facilitation of hippocampal serotonergic, but not noradrenergic, neurotransmission in the dorsal hippocampus facilitates adaptation to severe inescapable stress. Antidepressant effects of noradrenaline-selective drugs seem to depend on other structures than the dorsal hippocampus.

Early network activity propagates bidirectionally between hippocampus and cortex.

PubMed

Barger, Zeke; Easton, Curtis R; Neuzil, Kevin E; Moody, William J

2016-06-01

Spontaneous activity in the developing brain helps refine neuronal connections before the arrival of sensory-driven neuronal activity. In mouse neocortex during the first postnatal week, waves of spontaneous activity originating from pacemaker regions in the septal nucleus and piriform cortex propagate through the neocortex. Using high-speed Ca(2+) imaging to resolve the spatiotemporal dynamics of wave propagation in parasagittal mouse brain slices, we show that the hippocampus can act as an additional source of neocortical waves. Some waves that originate in the hippocampus remain restricted to that structure, while others pause at the hippocampus-neocortex boundary and then propagate into the neocortex. Blocking GABAergic neurotransmission decreases the likelihood of wave propagation into neocortex, whereas blocking glutamatergic neurotransmission eliminates spontaneous and evoked hippocampal waves. A subset of hippocampal and cortical waves trigger Ca(2+) waves in astrocytic networks after a brief delay. Hippocampal waves accompanied by Ca(2+) elevation in astrocytes are more likely to propagate into the neocortex. Finally, we show that two structures in our preparation that initiate waves-the hippocampus and the piriform cortex-can be electrically stimulated to initiate propagating waves at lower thresholds than the neocortex, indicating that the intrinsic circuit properties of those regions are responsible for their pacemaker function. © 2015 Wiley Periodicals, Inc.

Hippocampal memory consolidation during sleep: a comparison of mammals and birds

PubMed Central

Rattenborg, Niels C.; Martinez-Gonzalez, Dolores; Roth, Timothy C.; Pravosudov, Vladimir V.

2010-01-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region – the caudolateral nidopallium (NCL) – involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. PMID:21070585

Hippocampal memory consolidation during sleep: a comparison of mammals and birds.

PubMed

Rattenborg, Niels C; Martinez-Gonzalez, Dolores; Roth, Timothy C; Pravosudov, Vladimir V

2011-08-01

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow-wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow-oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high-order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow-oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp-wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7-14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow-oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow-oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region--the caudolateral nidopallium (NCL)--involved in performing high-order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra-hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow-oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow-oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups. © 2010 The Authors. Biological Reviews © 2010 Cambridge Philosophical Society.

Proteomic analysis of the dorsal and ventral hippocampus of rats maintained on a high fat and refined sugar diet.

PubMed

Francis, Heather M; Mirzaei, Mehdi; Pardey, Margery C; Haynes, Paul A; Cornish, Jennifer L

2013-10-01

The typical Western diet, rich in high saturated fat and refined sugar (HFS), has been shown to increase cognitive decline with aging and Alzheimer's disease, and to affect cognitive functions that are dependent on the hippocampus, including memory processes and reversal learning. To investigate neurophysiological changes underlying these impairments, we employed a proteomic approach to identify differentially expressed proteins in the rat dorsal and ventral hippocampus following maintenance on an HFS diet. Rats maintained on the HFS diet for 8 weeks were impaired on a novel object recognition task that assesses memory and on a Morris Water Maze task assessing reversal learning. Quantitative label-free shotgun proteomic analysis was conducted on biological triplicates for each group. For the dorsal hippocampus, 59 proteins were upregulated and 36 downregulated in the HFS group compared to controls. Pathway ana-lysis revealed changes to proteins involved in molecular transport and cellular and molecular signaling, and changes to signaling pathways including calcium signaling, citrate cycle, and oxidative phosphorylation. For the ventral hippocampus, 25 proteins were upregulated and 27 downregulated in HFS fed rats. Differentially expressed proteins were involved in cell-to-cell signaling and interaction, and cellular and molecular function. Changes to signaling pathways included protein ubiquitination, ubiquinone biosynthesis, oxidative phosphorylation, and mitochondrial dysfunction. This is the first shotgun proteomics study to examine protein changes in the hippocampus following long-term consumption of a HFS diet, identifying changes to a large number of proteins including those involved in synaptic plasticity and energy metabolism. All MS data have been deposited in the ProteomeXchange with identifier PXD000028. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimulus familiarity modulates functional connectivity of the perirhinal cortex and anterior hippocampus during visual discrimination of faces and objects

PubMed Central

McLelland, Victoria C.; Chan, David; Ferber, Susanne; Barense, Morgan D.

2014-01-01

Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information. PMID:24624075

Effects of Long Term Exposure of 900-1800 MHz Radiation Emitted from 2G Mobile Phone on Mice Hippocampus- A Histomorphometric Study.

PubMed

Mugunthan, Narayanaperumal; Shanmugasamy, Kathirvelu; Anbalagan, Jayaram; Rajanarayanan, Swamynathan; Meenachi, Swamynathan

2016-08-01

The advancement in the telecommunications technology with multi-functional added features in mobile phone, attracts more users of all age group. It is alarming to note that, the mobile phone use has increased amongst children and they are exposed to potentially harmful radiofrequency radiation in their lifetime. To investigate the long term exposure of 900 to 1800 MHz radiations emitted from 2G mobile phone in mice hippocampus at histomorphometric level. With due approval from institutional animal ethics committee, 36 mice were exposed to 2G mobile phone radiation, 48 minutes per day for a period of 30-180 days. The control group was kept under similar conditions without 2G exposure. Mice were sacrificed and the brain was removed from the first month to six months period. Brain was removed from the cranial cavity and hippocampus region was dissected out carefully and processed for routine histological study. Random serial sections were analysed under microscope for histomorphometric changes. For statistical analysis, independent t-test was used for comparing control and 2G exposed groups. The mean density of neurons in the hippocampus regions CA1, CA2 and DGDB from first to sixth month was significantly lower in the 2G exposed groups; however, in CA3 and DGVB, the 2G exposed mice showed significantly higher density of neurons. The mean nuclear diameter of neurons in the hippocampus region of CA1, CA2, CA3, DGDB and DGVB from first to sixth months showed lower nuclear diameter in 2G exposed mice. The long term exposure to 900-1800 MHz frequency radiations emitted from 2G mobile phone could cause significantly reduced neuron density and decreased nuclear diameter in the hippocampus neurons of mice.

Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

PubMed

Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

2018-01-01

The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

The effect of chronic mild stress on tumor-bearing rats' behavior and its mechanism.

PubMed

Xiu, Li-Juan; Lin, Hui-Ming; Wei, Pin-Kang

2010-03-31

Much evidence has demonstrated that stress and tumor interact, but the mechanisms are poorly understood. The purpose of this study is to discuss the effect of unpredictable chronic mild stress (CMS) upon the behavior of Walker 256 tumor-bearing rats and its mechanism. Observe the effects of CMS on the sucrose consumption, activities, body weight and levels of serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats, and on the levels of Bcl-2 and the phosphor-ERK1/2 in their hippocampus. CMS can reduce the average sucrose consumption, behavioral scores, body weight gain, expression of Bcl-2 and p-ERK1/2 protein in hippocampus, and increase serums TNF-alpha and IL-6 of both tumor-bearing rats and non-tumor-bearing rats. The stressed tumor-bearing rats had less sucrose consumption, body weight gain and lower behavioral scores, but higher level of serum TNF-alpha than stressed non-tumor-bearing rats. A negative correlation was found between the levels of serum TNF-alpha and sucrose consumption, while a positive correlation between the expression of Bcl-2 protein in hippocampus proper and sucrose consumption. CMS can reduce the protein levels of Bcl-2 and p-ERK1/2 in the rats' hippocampus, which contributes to the changes in the rats' behavior caused by CMS. Tumor-bearing rats are prone to behave depressively after the exposure to CMS. Our findings have suggested that the tumor, by increasing the inflammatory reaction, can be taken as a stressor, affecting the hippocampus and consequently causing depression by decreasing the expression of Bcl-2 and p-ERK1/2 in hippocampus. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats.

PubMed

Yonguc, Goksin Nilufer; Dodurga, Yavuz; Adiguzel, Esat; Gundogdu, Gulsah; Kucukatay, Vural; Ozbal, Seda; Yilmaz, Ismail; Cankurt, Ulker; Yilmaz, Yusuf; Akdogan, Ilgaz

2015-01-25

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic+GSE) and vitamin E (Diabetic+Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic+GSE and Diabetic+Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic+GSE (more prominently) and Diabetic+Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were significantly increased compared to Control. In Diabetic+GSE and Diabetic+Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB genes in the Diabetic+GSE group and the expression of caspase-3 and -9, TNF-α, and NF-κB genes in the Diabetic+Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Hippocampus Is Place of Interaction between Unconscious and Conscious Memories

PubMed Central

Züst, Marc Alain; Colella, Patrizio; Reber, Thomas Peter; Vuilleumier, Patrik; Hauf, Martinus; Ruch, Simon; Henke, Katharina

2015-01-01

Recent evidence suggests that humans can form and later retrieve new semantic relations unconsciously by way of hippocampus—the key structure also recruited for conscious relational (episodic) memory. If the hippocampus subserves both conscious and unconscious relational encoding/retrieval, one would expect the hippocampus to be place of unconscious-conscious interactions during memory retrieval. We tested this hypothesis in an fMRI experiment probing the interaction between the unconscious and conscious retrieval of face-associated information. For the establishment of unconscious relational memories, we presented subliminal (masked) combinations of unfamiliar faces and written occupations (“actor” or “politician”). At test, we presented the former subliminal faces, but now supraliminally, as cues for the reactivation of the unconsciously associated occupations. We hypothesized that unconscious reactivation of the associated occupation—actor or politician—would facilitate or inhibit the subsequent conscious retrieval of a celebrity’s occupation, which was also actor or politician. Depending on whether the reactivated unconscious occupation was congruent or incongruent to the celebrity’s occupation, we expected either quicker or delayed conscious retrieval process. Conscious retrieval was quicker in the congruent relative to a neutral baseline condition but not delayed in the incongruent condition. fMRI data collected during subliminal face-occupation encoding confirmed previous evidence that the hippocampus was interacting with neocortical storage sites of semantic knowledge to support relational encoding. fMRI data collected at test revealed that the facilitated conscious retrieval was paralleled by deactivations in the hippocampus and neocortical storage sites of semantic knowledge. We assume that the unconscious reactivation has pre-activated overlapping relational representations in the hippocampus reducing the neural effort for conscious retrieval. This finding supports the notion of synergistic interactions between conscious and unconscious relational memories in a common, cohesive hippocampal-neocortical memory space. PMID:25826338

Functional cross‐hemispheric shift between object‐place paired associate memory and spatial memory in the human hippocampus

PubMed Central

Lee, Choong‐Hee; Ryu, Jungwon; Lee, Sang‐Hun; Kim, Hakjin

2016-01-01

ABSTRACT The hippocampus plays critical roles in both object‐based event memory and spatial navigation, but it is largely unknown whether the left and right hippocampi play functionally equivalent roles in these cognitive domains. To examine the hemispheric symmetry of human hippocampal functions, we used an fMRI scanner to measure BOLD activity while subjects performed tasks requiring both object‐based event memory and spatial navigation in a virtual environment. Specifically, the subjects were required to form object‐place paired associate memory after visiting four buildings containing discrete objects in a virtual plus maze. The four buildings were visually identical, and the subjects used distal visual cues (i.e., scenes) to differentiate the buildings. During testing, the subjects were required to identify one of the buildings when cued with a previously associated object, and when shifted to a random place, the subject was expected to navigate to the previously chosen building. We observed that the BOLD activity foci changed from the left hippocampus to the right hippocampus as task demand changed from identifying a previously seen object (object‐cueing period) to searching for its paired‐associate place (object‐cued place recognition period). Furthermore, the efficient retrieval of object‐place paired associate memory (object‐cued place recognition period) was correlated with the BOLD response of the left hippocampus, whereas the efficient retrieval of relatively pure spatial memory (spatial memory period) was correlated with the right hippocampal BOLD response. These findings suggest that the left and right hippocampi in humans might process qualitatively different information for remembering episodic events in space. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. PMID:27009679

Orthogonal wave propagation of epileptiform activity in the planar mouse hippocampus in vitro.

PubMed

Kibler, Andrew B; Durand, Dominique M

2011-09-01

In vitro brain preparations have been used extensively to study the generation and propagation of epileptiform activity. Transverse and longitudinal slices of the rodent hippocampus have revealed various patterns of propagation. Yet intact connections between the transverse and longitudinal pathways should generate orthogonal (both transverse and longitudinal) propagation of seizures involving the entire hippocampus. This study utilizes the planar unfolded mouse hippocampus preparation to reveal simultaneous orthogonal epileptiform propagation and to test a method of arresting propagation. This study utilized an unfolded mouse hippocampus preparation. It was chosen due to its preservation of longitudinal neuronal processes, which are thought to play an important role in epileptiform hyperexcitability. 4-Aminopyridine (4-AP), microelectrodes, and voltage-sensitive dye imaging were employed to investigate tissue excitability. In 50-μm 4-AP, stimulation of the stratum radiatum induced transverse activation of CA3 cells but also induced a longitudinal wave of activity propagating along the CA3 region at a speed of 0.09 m/s. Without stimulation, a wave originated at the temporal CA3 and propagated in a temporal-septal direction could be suppressed with glutamatergic receptor antagonists. Orthogonal propagation traveled longitudinally along the CA3 pathway, secondarily invading the CA1 region at a velocity of 0.22 ± 0.024 m/s. Moreover, a local lesion restricted to the CA3 region could arrest wave propagation. These results reveal a complex two-dimensional epileptiform wave propagation pattern in the hippocampus that is generated by a combination of synaptic transmission and axonal propagation in the CA3 recurrent network. Epileptiform propagation block via a transverse selective CA3 lesion suggests a potential surgical technique for the treatment of temporal lobe epilepsy. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Orthogonal Wave Propagation of Epileptiform Activity in the Planar Mouse Hippocampus in vitro

PubMed Central

Kibler, Andrew B; Durand, Dominique M

2011-01-01

Purpose In vitro brain preparations have been used extensively to study the generation and propagation of epileptiform activity. Transverse and longitudinal slices of the rodent hippocampus have revealed various patterns of propagation. Yet intact connections between the transverse and longitudinal pathways should generate orthogonal (both transverse and longitudinal) propagation of seizures involving the entire hippocampus. This study utilizes the planar unfolded mouse hippocampus preparation to reveal simultaneous orthogonal epileptiform propagation and to test a method of arresting propagation. Methods This study utilized an unfolded mouse hippocampus preparation. It was chosen due to its preservation of longitudinal neuronal processes which are thought to play an important role in epileptiform hyper-excitability. 4-aminopyridine (4-AP), micro-electrodes, and voltage sensitive dye imaging were employed to investigate tissue excitability. Key Findings In 50 μM 4-AP, stimulation of the stratum radiatum induced transverse activation of CA3 cells but also induced a longitudinal wave of activity propagating along the CA3 region at a speed of 0.09 m/s. Without stimulation, a wave originated at the temporal CA3 and propagated in a temporal–septal direction and could be suppressed with glutamatergic antagonists. Orthogonal propagation traveled longitudinally along the CA3 pathway, secondarily invading the CA1 region at a velocity of 0.22±0.024 m/s. Moreover, a local lesion restricted to the CA3 region could arrest wave propagation. Significance These results reveal a complex two-dimensional epileptiform wave propagation pattern in the hippocampus that is generated by a combination of synaptic transmission and axonal propagation in the CA3 recurrent network. Epileptiform propagation block via a transverse selective CA3 lesion suggests a potential surgical technique for the treatment of temporal lobe epilepsy. PMID:21668440

Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

PubMed

Stefanovic, Bojana; Spasojevic, Natasa; Jovanovic, Predrag; Jasnic, Nebojsa; Djordjevic, Jelena; Dronjak, Sladjana

2016-10-01

The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS. This entailed quantifying the norephinephrine, mRNA and protein levels of DBH, NET, VMAT 2, MAO-A and COMT. The results show that CUMS evoked prolonged immobility. Melatonin treatment decreased immobility in comparison with the placebo group, reflecting an antidepressant-like effect. Compared with the placebo group, a dramatic decrease in norepinephrine content, decreased VMAT2 mRNA and protein and increased MAO-A protein levels in the hippocampus of the CUMS rats were observed. However, no significant differences in the levels of DBH, NET, COMT mRNA and protein and MAO-A mRNA levels between the placebo and the stressed groups were found. The results showed the restorative effects of melatonin on the stress-induced decline in the norepinephrine content of the hippocampus. It was observed that melatonin treatment in the CUMS rats prevented the stress-induced decrease in VMAT2 mRNA and protein levels, whereas it reduced the increase of the mRNA of COMT and protein levels of MAO-A. Chronic treatment with melatonin failed to alter the gene expression of DBH or NET in the hippocampus of the CUMS rats. Additionally, the results show that melatonin enhances VMAT2 expression and norepinephrine storage, whilst it reduces norepinephrine degrading enzymes. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Different Hippocampus Functional Connectivity Patterns in Healthy Young Adults with Mutations of APP/Presenilin-1/2 and APOEε4.

PubMed

Zheng, Li Juan; Su, Yun Yan; Wang, Yun Fei; Schoepf, U Joseph; Varga-Szemes, Akos; Pannell, Jonathan; Liang, Xue; Zheng, Gang; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

2018-04-01

This study aims to explore the hippocampus-based functional connectivity patterns in young, healthy APP and/or presenilin-1/2 mutation carriers and APOE ε4 subjects. Seventy-eight healthy young adults (33 male, mean age 24.0 ± 2.2 years; 18 APP and/or presenilin1/2 mutation carriers [APP/presenilin-1/2 group], 30 APOE ε4 subjects [APOE ε4 group], and 30 subjects without the above-mentioned genes [control group]) underwent resting-state functional MR imaging and neuropsychological assessments. Bilateral hippocampus functional connectivity patterns were compared among three groups. The brain regions with statistical differences were then extracted, and correlation analyses were performed between Z values of the brain regions and neuropsychological results. Compared with control group, both APOE ε4 group and APP/presenilin-1/2 group showed increased functional connectivity in medial prefrontal cortex and precuneus for the seeds of bilateral hippocampi. The APOE ε4 group displayed increased functional connectivity from bilateral hippocampi to the left middle temporal gyrus compared with the control group. Moreover, compared with the APP/presenilin-1/2 group, the APOE ε4 group also had markedly increased functional connectivity in right hippocampus-left middle temporal gyrus. The Z values of right hippocampus-left middle temporal gyrus correlated with various neuropsychological results across all the subjects, as well as in APOE ε4 group. Young healthy adults carrying APOE ε4 and APP/presenilin-1/2 displayed different hippocampus functional connectivity patterns, which may underlie the discrepant mechanisms of gene-modulated cognitive dysfunction in Alzheimer's disease.

Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes.

PubMed

Yue, Yun; Hu, Ling; Tian, Qin-jie; Jiang, Jing-mei; Dong, Yi-long; Jin, Zheng-yu; Cheng, Yu-hang; Hong, Xia; Ge, Qin-sheng; Zuo, Ping-ping

2007-08-01

To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4. Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Analysis with the apoE epsilon4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE epsilon3 carriers.

Cannabis-related episodic memory deficits and hippocampal morphological differences in healthy individuals and schizophrenia subjects.

PubMed

Smith, Matthew J; Cobia, Derin J; Reilly, James L; Gilman, Jodi M; Roberts, Andrea G; Alpert, Kathryn I; Wang, Lei; Breiter, Hans C; Csernansky, John G

2015-09-01

Cannabis use has been associated with episodic memory (EM) impairments and abnormal hippocampus morphology among both healthy individuals and schizophrenia subjects. Considering the hippocampus' role in EM, research is needed to evaluate the relationship between cannabis-related hippocampal morphology and EM among healthy and clinical groups. We examined differences in hippocampus morphology between control and schizophrenia subjects with and without a past (not current) cannabis use disorder (CUD). Subjects group-matched on demographics included 44 healthy controls (CON), 10 subjects with a CUD history (CON-CUD), 28 schizophrenia subjects with no history of substance use disorders (SCZ), and 15 schizophrenia subjects with a CUD history (SCZ-CUD). Large-deformation, high-dimensional brain mapping with MRI produced surface-based representations of the hippocampus that were compared across all four groups and correlated with EM and CUD history. Surface maps of the hippocampus were generated to visualize morphological differences. CON-CUD and SCZ-CUD were characterized by distinct cannabis-related hippocampal shape differences and parametric deficits in EM performance. Shape differences observed in CON-CUD were associated with poorer EM performance, while shape differences observed in SCZ-CUD were associated with a longer duration of CUD and shorter duration of CUD remission. A past history of CUD may be associated with notable differences in hippocampal morphology and EM impairments among adults with and without schizophrenia. Although the results may be compatible with a causal hypothesis, we must consider that the observed cannabis-related shape differences in the hippocampus could also be explained as biomarkers of a neurobiological susceptibility to poor memory or the effects of cannabis. © 2015 Wiley Periodicals, Inc.

Effect of electroacupuncture on brain-derived neurotrophic factor mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury.

PubMed

Zhao, Jianxin; Xu, Huazhou; Tian, Yuanxiang; Hu, Manxiang; Xiao, Hongling

2013-04-01

This work aims to observe the effects of electroacupuncture on brain-derived neurotrophic factor (BDNF) mRNA expression in mouse hippocampus following cerebral ischemia-reperfusion injury. The models of mouse cerebral ischemia-reperfusion injury were established. A total of 96 healthy mice were randomly assigned into 4 groups, namely, the sham surgery, model, model + electroacupuncture, and mode + hydergine groups. Mice in the model + electroacupuncture group were treated through electroacupuncture at the Shenshu (BL 23), Geshu (BL 17), and Baihui (GV 20) acupoints. Mice in the model+hydergine group were intragastrically administered with hydergine (0.77 mg/kg(-1) x day(-1)). The levels of BDNF mRNA expressions in the hippocampus were ana lyzed through a semi-quantitative reverse transcription-polymerase chain reaction assay on days 1 and 7 after the surgeries. BDNF mRNA expressions in the mouse hippocampus of the model group on days 1 and 7 after the surgery were higher than those of the sham surgery group (both P < 0.01). On days 1 and 7 of the electroacupuncture treatment, BDNF mRNA expression in the mouse hippocampus of the model + electroacupuncture group was significantly elevated compared with the model group (both P < 0.01) or the model + hydergine group (both P < 0.01). On days 1 and 7 of the hydergine treatment, BDNF mRNA expression in the mouse hippocampus of the model + hydergine group tended to increase compared with the model group; however, statistical significance was not achieved (both P > 0.05). Electroacupuncture treatment enhances endogenous BDNF expression, which may improve the survival environment for intracerebral neurons and inhibit the apoptosis of hippocampal cells.

Age-dependent changes in autophosphorylation of alpha calcium/calmodulin dependent kinase II in hippocampus and amygdala after contextual fear conditioning.

PubMed

Fang, Ton; Kasbi, Kamillia; Rothe, Stephanie; Aziz, Wajeeha; Giese, K Peter

2017-09-01

The hippocampus and amygdala are essential brain regions responsible for contextual fear conditioning (CFC). The autophosphorylation of alpha calcium-calmodulin kinase II (αCaMKII) at threonine-286 (T286) is a critical step implicated in long-term potentiation (LTP), learning and memory. However, the changes in αCaMKII levels with aging and training in associated brain regions are not fully understood. Here, we studied how aging and training affect the levels of phosphorylated (T286) and proportion of phosphorylated:total αCaMKII in the hippocampus and amygdala. Young and aged mice, naïve (untrained) and trained in CFC, were analysed by immunohistochemistry for the levels of total and phosphorylated αCaMKII in the hippocampus and amygdala. We found that two hours after CFC training, young mice exhibited a higher level of phosphorylated and increased ratio of phosphorylated:total αCaMKII in hippocampal CA3 stratum radiatum. Furthermore, aged untrained mice showed a higher ratio of phosphorylated:total αCaMKII in the CA3 region of the hippocampus when compared to the young untrained group. No effect of training or aging were seen in the central, lateral and basolateral amygdala regions, for both phosphorylated and ratio of phosphorylated:total αCaMKII. These results show that aging impairs the training-induced upregulation of autophosphorylated (T286) αCaMKII in the CA3 stratum radiatum of the hippocampus. This indicates that distinct age-related mechanisms underlie CFC that may rely more heavily on NMDA receptor-dependent plasticity in young age. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

PubMed

Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

2018-05-26

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

Sex differences and left-right asymmetries in expression of insulin and insulin-like growth factor-1 receptors in developing rat hippocampus.

PubMed

Hami, Javad; Sadr-Nabavi, Ariane; Sankian, Mojtaba; Haghir, Hossein

2012-04-01

Sex differences and laterality of rat hippocampus with respect to insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor (InsR) expression as two important contributors to/regulators of developmental and cognitive functions were examined using real-time PCR and western blot analysis at P0, P7 and P14. Expression of the IGF-1R gene was lowest at P0 in all studied hippocampi. In males, we found the highest expression at P7 in the right hippocampus, and at P14 in the left one. In contrast, the peaked IGF-1R expression occurred at P7 in female hippocampi independent of laterality. Hippocampal InsR expression in males decreased significantly between P0 and P7, followed by a marked upregulation at P14. Conversely, the expression of InsR in females peaked at P7 and then decreased again significantly at P14. We found significant interhemispheric differences in IGF-1R mRNA levels in both male and female hippocampi at different time points. In contrast, we only found significant interhemispheric differences in InsR mRNA expression in P14 male rats, with higher values in the left hippocampus. Interestingly, changes in mRNA expression and in protein levels followed the same developmental pattern, indicating that IGF-1R and InsR transcription is not subject to modulatory effects during the first two weeks of development. These findings indicate that there are prominent interhemispheric and sex differences in IGF-1R and InsR expression in the developing rat hippocampus, suggesting a probable mechanism for the control of gender and laterality differences in development and function of the hippocampus.

Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ebersole, B.L.J.

The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies ofmore » brain areas from mice that received injections of (/sup 3/H)LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free (/sup 3/H)LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.« less

Source recognition by stimulus content in the MTL.

PubMed

Park, Heekyeong; Abellanoza, Cheryl; Schaeffer, James; Gandy, Kellen

2014-03-17

Source memory is considered to be the cornerstone of episodic memory that enables us to discriminate similar but different events. In the present fMRI study, we investigated whether neural correlates of source retrieval differed by stimulus content in the medial temporal lobe (MTL) when the item and context had been integrated as a perceptually unitized entity. Participants were presented with a list of items either in verbal or pictorial form overlaid on a colored square and instructed to integrate both the item and context into a single image. At test, participants judged the study status of test items and the color in which studied items were presented. Source recognition invariant of stimulus content elicited retrieval activity in both the left anterior hippocampus extending to the perirhinal cortex and the right posterior hippocampus. Word-selective source recognition was related to activity in the left perirhinal cortex, whereas picture-selective source recognition was identified in the left posterior hippocampus. Neural activity sensitive to novelty detection common to both words and pictures was found in the left anterior and right posterior hippocampus. Novelty detection selective to words was associated with the left perirhinal cortex, while activity sensitive to new pictures was identified in the bilateral hippocampus and adjacent MTL cortices, including the parahippocampal, entorhinal, and perirhinal cortices. These findings provide further support for the integral role of the hippocampus both in source recognition and in detection of new stimuli across stimulus content. Additionally, novelty effects in the MTL reveal the integral role of the MTL cortex as the interface for processing new information. Collectively, the present findings demonstrate the importance of the MTL for both previously experienced and novel events. Copyright © 2014 Elsevier B.V. All rights reserved.

A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats

PubMed Central

Jung, Marianna E.; Metzger, Daniel B.

2016-01-01

Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2•−, malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2’s protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2’s antioxidant protection for hippocampus-related behavior. PMID:27503149

Dengue-3 encephalitis promotes anxiety-like behavior in mice.

PubMed

de Miranda, Aline Silva; Rodrigues, David Henrique; Amaral, Débora Cristina Guerra; de Lima Campos, Roberta Dayrell; Cisalpino, Daniel; Vilela, Márcia Carvalho; Lacerda-Queiroz, Norinne; de Souza, Kátia Paulino Ribeiro; Vago, Juliana Priscila; Campos, Marco Antônio; Kroon, Erna Geesien; da Glória de Souza, Danielle; Teixeira, Mauro Martins; Teixeira, Antônio Lúcio; Rachid, Milene Alvarenga

2012-04-21

Dengue virus is a human pathogen that may cause meningoencephalitis and other neurological syndromes. The current study investigated anxiety-like behavior and expression of proinflammatory cytokines and pro-apoptotic caspase-3 in the hippocampus of C57BL/6 mice infected with non-adapted Dengue virus 3 genotype I (DENV-3) inoculated intracranially with 4×10(3) (plaque-forming unit) PFU. Anxiety-like behavior was assessed in control and DENV-3 infected mice using the elevated plus maze. The open field test was performed to evaluate locomotor activity. Histopathological changes in CA regions of the hippocampus were assessed by haematoxylin and eosin staining. Immunoreactive and protein levels of cleaved caspase-3 were also analyzed in the hippocampus. The mRNA expression of IL-6 and TNF-α in the hippocampus were estimated by quantitative real time (polymerase chain reaction) PCR. All procedures were conducted on day 5 post-infection. We found that DENV-3 infected mice presented higher levels of anxiety in comparison with controls (p≤0.05). No difference in motor activity was found between groups (p=0.77). The infection was followed by a significant increase of TNF-α and IL-6 mRNA expression in the hippocampus (p≤0.05). Histological analysis demonstrated meningoencephalitis with formation of perivascular cuffs, infiltration of immune cells and loss of neurons at CA regions of hippocampus. Numerous caspase-3 positive neurons were visualized at CA areas in DENV-3 infected mice. Marked increase of cleaved caspase-3 levels were observed after infection. This study described anxiety-like behavior, hippocampal inflammation and neuronal apoptosis associated with DENV-3 infection in the central nervous system. Copyright © 2012 Elsevier B.V. All rights reserved.

Transient impairment of hippocampus-dependent learning and memory in relatively low-dose of acute radiation syndrome is associated with inhibition of hippocampal neurogenesis.

PubMed

Kim, Joong-Sun; Lee, Hae-June; Kim, Jong Choon; Kang, Seong Soo; Bae, Chun-Sik; Shin, Taekyun; Jin, Jae-Kwang; Kim, Sung Ho; Wang, Hongbing; Moon, Changjong

2008-09-01

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.

Developmental changes in hippocampal shape among preadolescent children.

PubMed

Lin, Muqing; Fwu, Peter T; Buss, Claudia; Davis, Elysia P; Head, Kevin; Muftuler, L Tugan; Sandman, Curt A; Su, Min-Ying

2013-11-01

It is known that the largest developmental changes in the hippocampus take place during the prenatal period and during the first two years of postnatal life. Few studies have been conducted to address the normal developmental trajectory of the hippocampus during childhood. In this study shape analysis was applied to study the normal developing hippocampus in a group of 103 typically developing 6- to 10-year-old preadolescent children. The individual brain was normalized to a template, and then the hippocampus was manually segmented and further divided into the head, body, and tail sub-regions. Three different methods were applied for hippocampal shape analysis: radial distance mapping, surface-based template registration using the robust point matching (RPM) algorithm, and volume-based template registration using the Demons algorithm. All three methods show that the older children have bilateral expanded head segments compared to the younger children. The results analyzed based on radial distance to the centerline were consistent with those analyzed using template-based registration methods. In analyses stratified by sex, it was found that the age-associated anatomical changes were similar in boys and girls, but the age-association was strongest in girls. Total hippocampal volume and sub-regional volumes analyzed using manual segmentation did not show a significant age-association. Our results suggest that shape analysis is sensitive to detect sub-regional differences that are not revealed in volumetric analysis. The three methods presented in this study may be applied in future studies to investigate the normal developmental trajectory of the hippocampus in children. They may be further applied to detect early deviations from the normal developmental trajectory in young children for evaluating susceptibility for psychopathological disorders involving hippocampus. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Changes in acetylcholinesterase, Na+,K+-ATPase, and Mg2+-ATPase activities in the frontal cortex and the hippocampus of hyper- and hypothyroid adult rats.

PubMed

Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

2007-08-01

The thyroid hormones (THs) are crucial determinants of normal development and metabolism, especially in the central nervous system. The metabolic rate is known to increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na+,K+)- and Mg2+-adenosinetriphosphatase (ATPase) in the frontal cortex and the hippocampus of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, and hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. A region-specific behavior was observed concerning the examined enzyme activities in hyper- and hypothyroidism. In hyperthyroidism, AChE activity was significantly increased only in the hippocampus (+22%), whereas Na+,K+-ATPase activity was significantly decreased in the hyperthyroid rat hippocampus (-47%) and remained unchanged in the frontal cortex. In hypothyroidism, AChE activity was significantly decreased in the frontal cortex (-23%) and increased in the hippocampus (+21%). Na+,K+-ATPase activity was significantly decreased in both the frontal cortex (-35%) and the hippocampus (-43%) of hypothyroid rats. Mg2+-ATPase remained unchanged in the regions of both hyper- and hypothyroid rat brains. Our data revealed that THs affect the examined adult rat brain parameters in a region- and state-specific way. The TH-reduced Na+,K+-ATPase activity may increase the synaptic acetylcholine release and, thus, modulate AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems in the examined brain regions.

The effects of aging, housing and ibuprofen treatment on brain neurochemistry in a triple transgene Alzheimer's disease mouse model using magnetic resonance spectroscopy and imaging.

PubMed

Choi, Ji-Kyung; Carreras, Isabel; Aytan, Nur; Jenkins-Sahlin, Eric; Dedeoglu, Alpaslan; Jenkins, Bruce G

2014-11-24

We investigated a triple transgene Alzheimer's disease (AD) mouse model that recapitulates many of the neurochemical, anatomic, pathologic and behavioral defects seen in human AD. We studied the mice as a function of age and brain region and investigated potential therapy with the non-steroidal anti-inflammatory drug ibuprofen. Magnetic resonance spectroscopy (MRS) showed alterations characteristic of AD (i.e. increased myo-inositol and decreased N-acetylaspartate (NAA)). Mice at 6 months of age showed an increase in myo-inositol in the hippocampus at a time when the Aβ is intracellular, but not in amygdala or cortex. Myo-inositol increased as a function of age in the amygdala, cortex and striatum while NAA decreased only in the hippocampus and cortex at 17-23 months of age. Ibuprofen protected the increase of myo-inositol at six months of age in the hippocampus, but had no effect at 17-23 months of age (a time when Aβ is extracellular). In vivo MRI and MRS showed that at 17-23 months of age there was a significant protective effect of ibuprofen on hippocampal volume and NAA loss. Together, these data show the following: the increase in myo-inositol occurs before the decrease in NAA in hippocampus but not cortex; the hippocampus shows earlier changes than does the amygdale or cortex consistent with earlier deposition of Aβ40-42 in the hippocampus and ibuprofen protects against multiple components of the AD pathology. These data also show a profound effect of housing on this particular mouse model. Published by Elsevier B.V.

Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.

PubMed

Curtis, J M R; Santos, S V; Nadeau, J L; Gunn, B; Bigney Wilner, K; Balasubramanian, H; Overington, S; Lesage, C-M; D'entremont, J; Wieckowski, K

2017-12-01

To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m -2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (L S ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m 2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L ∞  = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment. © 2017 The Fisheries Society of the British Isles.

[Effects of Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats].

PubMed

Tong, Hai-Ying; Wu, Jisiguleng; Bai, Liang-Feng; Bao, Wu-Ye; Hu, Rilebagen; Li, Jing; Zhang, Yue

2014-05-01

To observe the effects of Mongolian pharmaceutical Betel shisanwei ingredients pill on AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depressive rats. Sixty male Wistar rats were randomly divided into six groups according to the sugar consumption test (10 rats in each group), normal control group,model group,fluoxetine group (3.3 mg x kg(-1)) and low dose, medium dose and high dose group (0.25, 0.5, 1 g x kg(-1)) of Betel shisanwei ingredients pill. Except the normal control,the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely raising for 28 days. 10 mL x kg(-1) of drugs were given to each rat once daily,continuously for 28 days. The AC activity of the hippocampus and prefrontal cortex were determined by radiation immunity analysis (RIA), while cAMP and PKA quantity were determinated by Enzyme-linked immunosorbent (ELISA). The AC activity, cAMP and PKA quantity of hippocampus and prefrontal of mouse model of Chronic stress depression decreased significantly than those of control group (P < 0.05 or P < 0.01). However, the AC activity, cAMP and PKA quantity of rat hippocampus and prefrontal cortex in the fluoxetine group and the Mongolian pharmaceutical Betel shisanwei ingredients pill group indecreased significantly than those of model group (P < 0.01 or P < 0.05). Especially for the high dose group of Mongolian pharmaceutical Betel shisanwei ingredients pill. The AC-cAMP-PKA signal transduction pathways in hippocampus and prefrontal cortex of depression model of rats is down-regulated, whereas Mongolian pharmaceutical Betel shisanwei ingredients pill could up-regulated it to resist depression.

Inter-individual differences in serotonin and glutamate co-transmission reflect differentiation in context-induced conditioned 50-kHz USVs response after morphine withdrawal.

PubMed

Hamed, Adam; Kursa, Miron Bartosz

2018-05-17

A growing body of research provides compelling evidence that in rats 50-kHz USVs are a form of expression of positive emotions. Context-induced 50-kHz USVs emission is variable among rats, indicating individual differences in contextual response bound up with pharmacological reward. The aims of this study were to: extract the most important neurotransmitters related to context-induced conditioned 50-kHz USVs response; find biological basis of existing inter-individual differences in context-induced conditioned 50-kHz USVs response; create a model of all-to-all neurotransmitters correlations. The data collected here confirms that re-exposure to the context of morphine administration after the withdrawal period increases the level of 50-kHz USVs and this contextual response is associated with elevated serotonin concentrations in amygdala, hippocampus and mPFC and with increased Glu/Gln ratio in nucleus accumbens. The concentration of serotonin increases simultaneously in amygdala, nucleus accumbens and hippocampus. Moreover, 5-HT concentration in amygdala is bound up with glutamate level in this structure as well as in hippocampus. Furthermore, Glu/Gln ratio in nucleus accumbens has strong associations with Glu/Gln ratio simultaneously in VTA, amygdala, striatum and hippocampus. All-to-all-analysis indicate that concentration of glutamate in hippocampus is proportional to glutamate in VTA and GABA concentration in the hippocampus. We have also demonstrated that Glu/GABA ratio in VTA and amygdala was elevated after post withdrawal re-exposure to the pharmacological reward paired context. Presented analysis indicates a strong correlation between serotonergic and glutamatergic systems in context-induced conditioned response. The strength of this co-transmission correlates with the number of 50-kHz USVs emitted in response to morphine-paired context.

Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

PubMed

Murtuza, Mohammad I; Isokawa, Masako

2018-01-01

Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

Parvalbumin and neuropeptide Y expressing hippocampal GABA-ergic inhibitory interneuron numbers decline in a model of Gulf War illness.

PubMed

Megahed, Tarick; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2014-01-01

Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf War illness (GWI). Combined exposure to the nerve gas antidote pyridostigmine bromide (PB), pesticides and stress during the Persian Gulf War-1 (PGW-1) are presumed to be among the major causes of GWI. Indeed, our recent studies in rat models have shown that exposure to GWI-related (GWIR) chemicals and mild stress for 4 weeks engenders cognitive impairments accompanied with several detrimental changes in the hippocampus. In this study, we tested whether reduced numbers of hippocampal gamma-amino butyric acid (GABA)-ergic interneurons are among the pathological changes induced by GWIR-chemicals and stress. Animals were exposed to low doses of GWIR-chemicals and mild stress for 4 weeks. Three months after this exposure, subpopulations of GABA-ergic interneurons expressing the calcium binding protein parvalbumin (PV), the neuropeptide Y (NPY) and somatostatin (SS) in the hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals and stress for 4 weeks displayed reduced numbers of PV-expressing GABA-ergic interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and CA3 subfields. However, no changes in SS+ interneuron population were observed in the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals was associated with greatly diminished hippocampus neurogenesis. Because PV+ and NPY+ interneurons play roles in maintaining normal cognitive function and neurogenesis, and controlling the activity of excitatory neurons in the hippocampus, reduced numbers of these interneurons may be one of the major causes of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence, strategies that improve inhibitory neurotransmission in the hippocampus may prove beneficial for reversing cognitive dysfunction in GWI.

Aged rats are more vulnerable than adolescents to "ecstasy"-induced toxicity.

PubMed

Feio-Azevedo, R; Costa, V M; Barbosa, D J; Teixeira-Gomes, A; Pita, I; Gomes, S; Pereira, F C; Duarte-Araújo, M; Duarte, J A; Marques, F; Fernandes, E; Bastos, M L; Carvalho, F; Capela, J P

2018-06-04

3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a widespread drug of abuse with known neurotoxic properties. The present study aimed to evaluate the differential toxic effects of MDMA in adolescent and aged Wistar rats, using doses pharmacologically comparable to humans. Adolescent (post-natal day 40) (3 × 5 mg/kg, 2 h apart) and aged (mean 20 months old) (2 × 5 mg/kg, 2 h apart) rats received MDMA intraperitoneally. Animals were killed 7 days later, and the frontal cortex, hippocampus, striatum and cerebellum brain areas were dissected, and heart, liver and kidneys were collected. MDMA caused hyperthermia in both treated groups, but aged rats had a more dramatic temperature elevation. MDMA promoted serotonergic neurotoxicity only in the hippocampus of aged, but not in the adolescents' brain, and did not change the levels of dopamine or serotonin metabolite in the striatum of both groups. Differential responses according to age were also seen regarding brain p-Tau levels, a hallmark of a degenerative brain, since only aged animals had significant increases. MDMA evoked brain oxidative stress in the hippocampus and striatum of aged, and in the hippocampus, frontal cortex, and striatum brain areas of adolescents according to protein carbonylation, but only decreased GSH levels in the hippocampus of aged animals. The brain maturational stage seems crucial for MDMA-evoked serotonergic neurotoxicity. Aged animals were more susceptible to MDMA-induced tissue damage in the heart and kidneys, and both ages had an increase in liver fibrotic tissue content. In conclusion, age is a determinant factor for the toxic events promoted by "ecstasy". This work demonstrated special susceptibility of aged hippocampus to MDMA neurotoxicity, as well as impressive damage to the heart and kidney tissue following "ecstasy".

Effects of genistein and swimming exercise on spatial memory and expression of microRNA 132, BDNF, and IGF-1 genes in the hippocampus of ovariectomized rats.

PubMed

Habibi, Parisa; Babri, Shirin; Ahmadiasl, Nasser; Yousefi, Hadi

2017-08-01

The aim of the present study was to investigate the effects of genistein and exercise on the spatial memory and expression of microRNA-132, BDNF, and IGF-1 in the hippocampus of ovariectomized rats. Sixty animals were divided into six groups of control, sham, ovariectomy (OVX), ovariectomized with 8 weeks of genistein administration (OVX.G), with 8 weeks of swimming training (OVX.E), and with 8 weeks of both of them (OVX.G.E). The effect of genistein and/or exercise was evaluated by measuring microRNA-132, BDNF, and IGF-1 expression levels in the hippocampus tissue. Grafts were analyzed using Real-time polymerase chain reaction for microRNA-132, BDNF, IGF-1, and spatial memory via a Morris water maze (MWM). Our findings showed that ovariectomy decreased the expression of microRNA-132, BDNF, and IGF-1 in the hippocampus ( P <0.05) in comparison with the sham group as well as performance in the water maze ( P <0.05). Also according to results ovariectomized groups that were treated with genistein/exercise or both of them showed significant difference in expression of microRNA-132, BDNF, and IGF-1 in the hippocampus ( P <0.05) and decreased latency in MWM ( P <0.05) compared with the OVX group but combination treatment was more effective in the OVX.G.E group in comparison with OVX.E and OVX.G groups. Overall our results emphasized that combination treatment with genistein and exercise could improve microRNA-132, BDNF, and IGF-1 expression in the hippocampus as well as the spatial memory of ovariectomized rats. These effects may have beneficial impacts on the menopausal period.

Alzheimer's disease pathology in the neocortex and hippocampus of the western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Perez, Sylvia E; Raghanti, Mary Ann; Hof, Patrick R; Kramer, Lynn; Ikonomovic, Milos D; Lacor, Pascale N; Erwin, Joseph M; Sherwood, Chet C; Mufson, Elliott J

2013-12-15

The two major histopathologic hallmarks of Alzheimer's disease (AD) are amyloid beta protein (Aβ) plaques and neurofibrillary tangles (NFT). Aβ pathology is a common feature in the aged nonhuman primate brain, whereas NFT are found almost exclusively in humans. Few studies have examined AD-related pathology in great apes, which are the closest phylogenetic relatives of humans. In the present study, we examined Aβ and tau-like lesions in the neocortex and hippocampus of aged male and female western lowland gorillas using immunohistochemistry and histochemistry. Analysis revealed an age-related increase in Aβ-immunoreactive plaques and vasculature in the gorilla brain. Aβ plaques were more abundant in the neocortex and hippocampus of females, whereas Aβ-positive blood vessels were more widespread in male gorillas. Plaques were also Aβ40-, Aβ42-, and Aβ oligomer-immunoreactive, but only weakly thioflavine S- or 6-CN-PiB-positive in both sexes, indicative of the less fibrillar (diffuse) nature of Aβ plaques in gorillas. Although phosphorylated neurofilament immunostaining revealed a few dystrophic neurites and neurons, choline acetyltransferase-immunoreactive fibers were not dystrophic. Neurons stained for the tau marker Alz50 were found in the neocortex and hippocampus of gorillas at all ages. Occasional Alz50-, MC1-, and AT8-immunoreactive astrocyte and oligodendrocyte coiled bodies and neuritic clusters were seen in the neocortex and hippocampus of the oldest gorillas. This study demonstrates the spontaneous presence of both Aβ plaques and tau-like lesions in the neocortex and hippocampus in old male and female western lowland gorillas, placing this species at relevance in the context of AD research. Copyright © 2013 Wiley Periodicals, Inc.

Lithium ameliorates lipopolysaccharide-induced neurotoxicity in the cortex and hippocampus of the adult rat brain.

PubMed

Khan, Muhammad Sohail; Ali, Tahir; Abid, Muhammad Noman; Jo, Myeung Hoon; Khan, Amjad; Kim, Min Woo; Yoon, Gwang Ho; Cheon, Eun Woo; Rehman, Shafiq Ur; Kim, Myeong Ok

2017-09-01

Lithium an effective mood stabilizer, primary used in the treatment of bipolar disorders, has been reported as a protective agent in various neurological disorders. In this study, we examined the neuroprotective role of lithium chloride (LiCl) against lipopolysaccharide (LPS) in the cortex and hippocampus of the adult rat brain. We determined that LiCl -attenuated LPS-induced activated toll-like receptor 4 (TLR4) signalling and significantly reduced the nuclear factor- k B (NF- K B) translation factor and various other inflammatory mediators such as interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α). We also analyzed that LiCl significantly abrogated activated gliosis via attenuation of specific markers for activated microglia, ionized calcium-binding adaptor molecule (Iba-1) and astrocytes, glial fibrillary acidic protein (GFAP) in both the cortex and hippocampus of the adult rat brain. Furthermore, we also observed that LiCl treatment significantly ameliorated the increase expression level of apoptotic neurodegeneration protein markers Bax/Bcl2, activated caspase-3 and poly (ADP-ribose) polymerase-1 (PARP-1) in the cortex and hippocampus regions of the LPS-treated adult rat brain. In addition, the morphological results of the fluoro-jade B (FJB) and Nissl staining showed that LiCl attenuated the neuronal degeneration in the cortex and hippocampus regions of the LPS-treated adult rat brain. Taken together, our Western blot and morphological results indicated that LiCl significantly prevents the LPS-induced neurotoxicity via attenuation of neuroinflammation and apoptotic neurodegeneration in the cortex and hippocampus of the adult rat brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

TIME-DEPENDENT NEUROBIOLOGICAL EFFECTS OF COLCHICINE ADMINISTERED DIRECTLY INTO THE HIPPOCAMPUS OF RATS (JOURNAL VERSION)

EPA Science Inventory

Rats were given bilateral injections of colchicine into the dorsal and ventral hippocampus. Behavioral, neurochemical and histopathological measurements were taken up to 12 weeks after surgery. Colchicine produced a consistent increase in spontaneous motor activity, enhanced acou...

New Methods for Understanding Systems Consolidation

ERIC Educational Resources Information Center

Tayler, Kaycie K.; Wiltgen, Brian J.

2013-01-01

According to the standard model of systems consolidation (SMC), neocortical circuits are reactivated during the retrieval of declarative memories. This process initially requires the hippocampus. However, with the passage of time, neocortical circuits become strengthened and can eventually retrieve memory without input from the hippocampus.…

Fronto-Limbic Functioning in Children and Adolescents with and without Autism

ERIC Educational Resources Information Center

Loveland, Katherine A.; Bachevalier, Jocelyne; Pearson, Deborah A.; Lane, David M.

2008-01-01

We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral prefrontal cortex and hippocampus (dorsolateral prefrontal-hippocampus), in 138 individuals aged 7-18 years, with and without autism. We predicted that performance on…

Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation

PubMed Central

Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

2016-01-01

The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains. PMID:26726963

HIPS: A new hippocampus subfield segmentation method.

PubMed

Romero, José E; Coupé, Pierrick; Manjón, José V

2017-12-01

The importance of the hippocampus in the study of several neurodegenerative diseases such as Alzheimer's disease makes it a structure of great interest in neuroimaging. However, few segmentation methods have been proposed to measure its subfields due to its complex structure and the lack of high resolution magnetic resonance (MR) data. In this work, we present a new pipeline for automatic hippocampus subfield segmentation using two available hippocampus subfield delineation protocols that can work with both high and standard resolution data. The proposed method is based on multi-atlas label fusion technology that benefits from a novel multi-contrast patch match search process (using high resolution T1-weighted and T2-weighted images). The proposed method also includes as post-processing a new neural network-based error correction step to minimize systematic segmentation errors. The method has been evaluated on both high and standard resolution images and compared to other state-of-the-art methods showing better results in terms of accuracy and execution time. Copyright © 2017 Elsevier Inc. All rights reserved.

When music and long-term memory interact: effects of musical expertise on functional and structural plasticity in the hippocampus.

PubMed

Groussard, Mathilde; La Joie, Renaud; Rauchs, Géraldine; Landeau, Brigitte; Chételat, Gaël; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis; Platel, Hervé

2010-10-05

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus.

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus

PubMed Central

Hurtado-Zavala, Joaquin I.; Ramachandran, Binu; Ahmed, Saheeb; Halder, Rashi; Bolleyer, Christiane; Awasthi, Ankit; Stahlberg, Markus A.; Wagener, Robin J.; Anderson, Kristin; Drenan, Ryan M.; Lester, Henry A.; Miwa, Julie M.; Staiger, Jochen F.; Fischer, Andre; Dean, Camin

2017-01-01

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine—via α2β2-containing nicotinic receptors—to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity. PMID:28722015

Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

PubMed

Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

2015-11-01

Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

Sevoflurane-induced down-regulation of hippocampal oxytocin and arginine vasopressin impairs juvenile social behavioral abilities.

PubMed

Zhou, Zhi-Bin; Yang, Xiao-Yu; Yuan, Bao-Long; Niu, Li-Jun; Zhou, Xue; Huang, Wen-Qi; Feng, Xia; Zhou, Li-Hua

2015-05-01

Cumulative evidence indicates that early childhood anesthesia can alter a child's future behavioral performance. Animal researchers have found that sevoflurane, the most commonly used anesthetic for children, can produce damage in the neonatal brains of rodents. To further investigate this phenomenon, we focused on the influence of sevoflurane anesthesia on the development of juvenile social behavioral abilities and the pro-social proteins oxytocin (OT) and arginine vasopressin (AVP) in the neonatal hippocampus. A single 6-h sevoflurane exposure for postnatal day 5 mice resulted in decreased OT and AVP messenger RNA (mRNA) and protein levels in the hippocampus. OT and AVP proteins became sparsely distributed in the dorsal hippocampus after the exposure to sevoflurane. Compared with the air-treated group, mice in the sevoflurane-treated group showed signs of impairment in social recognition memory formation and social discrimination ability. Sevoflurane anesthesia reduces OT and AVP activities in the neonatal hippocampus and impairs social recognition memory formation and social discrimination ability in juvenile mice.

Coordinated Acetylcholine Release in Prefrontal Cortex and Hippocampus Is Associated with Arousal and Reward on Distinct Timescales.

PubMed

Teles-Grilo Ruivo, Leonor M; Baker, Keeley L; Conway, Michael W; Kinsley, Peter J; Gilmour, Gary; Phillips, Keith G; Isaac, John T R; Lowry, John P; Mellor, Jack R

2017-01-24

Cholinergic neurotransmission throughout the neocortex and hippocampus regulates arousal, learning, and attention. However, owing to the poorly characterized timing and location of acetylcholine release, its detailed behavioral functions remain unclear. Using electrochemical biosensors chronically implanted in mice, we made continuous measurements of the spatiotemporal dynamics of acetylcholine release across multiple behavioral states. We found that tonic levels of acetylcholine release were coordinated between the prefrontal cortex and hippocampus and maximal during training on a rewarded working memory task. Tonic release also increased during REM sleep but was contingent on subsequent wakefulness. In contrast, coordinated phasic acetylcholine release occurred only during the memory task and was strongly localized to reward delivery areas without being contingent on trial outcome. These results show that coordinated acetylcholine release between the prefrontal cortex and hippocampus is associated with reward and arousal on distinct timescales, providing dual mechanisms to support learned behavior acquisition during cognitive task performance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local-global reference frames.

PubMed

Knierim, James J; Neunuebel, Joshua P; Deshmukh, Sachin S

2014-02-05

The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between 'where' versus 'what' needs revision. We propose a refinement of this model, which is more complex than the simple spatial-non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience.

Hippocampal gamma-band Synchrony and pupillary responses index memory during visual search.

PubMed

Montefusco-Siegmund, Rodrigo; Leonard, Timothy K; Hoffman, Kari L

2017-04-01

Memory for scenes is supported by the hippocampus, among other interconnected structures, but the neural mechanisms related to this process are not well understood. To assess the role of the hippocampus in memory-guided scene search, we recorded local field potentials and multiunit activity from the hippocampus of macaques as they performed goal-directed search tasks using natural scenes. We additionally measured pupil size during scene presentation, which in humans is modulated by recognition memory. We found that both pupil dilation and search efficiency accompanied scene repetition, thereby indicating memory for scenes. Neural correlates included a brief increase in hippocampal multiunit activity and a sustained synchronization of unit activity to gamma band oscillations (50-70 Hz). The repetition effects on hippocampal gamma synchronization occurred when pupils were most dilated, suggesting an interaction between aroused, attentive processing and hippocampal correlates of recognition memory. These results suggest that the hippocampus may support memory-guided visual search through enhanced local gamma synchrony. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reversible Information Flow across the Medial Temporal Lobe: The Hippocampus Links Cortical Modules during Memory Retrieval

PubMed Central

Cooper, Elisa; Henson, Richard N.

2013-01-01

A simple cue can be sufficient to elicit vivid recollection of a past episode. Theoretical models suggest that upon perceiving such a cue, disparate episodic elements held in neocortex are retrieved through hippocampal pattern completion. We tested this fundamental assumption by applying functional magnetic resonance imaging (fMRI) while objects or scenes were used to cue participants' recall of previously paired scenes or objects, respectively. We first demonstrate functional segregation within the medial temporal lobe (MTL), showing domain specificity in perirhinal and parahippocampal cortices (for object-processing vs scene-processing, respectively), but domain generality in the hippocampus (retrieval of both stimulus types). Critically, using fMRI latency analysis and dynamic causal modeling, we go on to demonstrate functional integration between these MTL regions during successful memory retrieval, with reversible signal flow from the cue region to the target region via the hippocampus. This supports the claim that the human hippocampus provides the vital associative link that integrates information held in different parts of cortex. PMID:23986252

Glutamatergic drive along the septo-temporal axis of hippocampus boosts prelimbic oscillations in the neonatal mouse

PubMed Central

Ahlbeck, Joachim; Song, Lingzhen; Chini, Mattia; Bitzenhofer, Sebastian H

2018-01-01

The long-range coupling within prefrontal-hippocampal networks that account for cognitive performance emerges early in life. The discontinuous hippocampal theta bursts have been proposed to drive the generation of neonatal prefrontal oscillations, yet the cellular substrate of these early interactions is still unresolved. Here, we selectively target optogenetic manipulation of glutamatergic projection neurons in the CA1 area of either dorsal or intermediate/ventral hippocampus at neonatal age to elucidate their contribution to the emergence of prefrontal oscillatory entrainment. We show that despite stronger theta and ripples power in dorsal hippocampus, the prefrontal cortex is mainly coupled with intermediate/ventral hippocampus by phase-locking of neuronal firing via dense direct axonal projections. Theta band-confined activation by light of pyramidal neurons in intermediate/ventral but not dorsal CA1 that were transfected by in utero electroporation with high-efficiency channelrhodopsin boosts prefrontal oscillations. Our data causally elucidate the cellular origin of the long-range coupling in the developing brain. PMID:29631696

Reduced Marker of Vascularization in the Anterior Hippocampus in a Female Monkey Model of Depression

PubMed Central

Kalidindi, Anisha; Kelly, Sean D.; Singleton, Kaela S.; Guzman, Dora; Merrill, Liana; Willard, Stephanie L.; Shively, Carol A.; Neigh, Gretchen N.

2016-01-01

Depression is a common and debilitating mood disorder that impacts women more often than men. The mechanisms that result in depressive behaviors are not fully understood; however, the hippocampus has been noted as a key structure in the pathophysiology of depression. In addition to neural implications of depression, the cardiovascular system is impacted. Although not as commonly considered, the cerebrovasculature is critical to brain function, impacted by environmental stimuli, and is capable of altering neural function and thereby behavior. In the current study, we assessed the relationship between depressive behavior and a marker of vascularization of the hippocampus in adult female cynomolgus macaques (Macaca fascicularis). Similar to previously noted impacts on neuropil and glia, the depressed phenotype predicts a reduction in a marker of vascular length in the anterior hippocampus. These data reinforce the growing recognition of the effects of depression on vasculature and support further consideration of vascular endpoints in studies aimed at the elucidation of the mechanisms underlying depression. PMID:27423324

Fibronectin domains of extracellular matrix molecule tenascin-C modulate hippocampal learning and synaptic plasticity.

PubMed

Strekalova, Tatyana; Sun, Mu; Sibbe, Mirjam; Evers, Matthias; Dityatev, Alexander; Gass, Peter; Schachner, Melitta

2002-09-01

The extracellular matrix molecule tenascin-C (TN-C) has been shown to be involved in hippocampal synaptic plasticity in vitro. Here, we describe a deficit in hippocampus-dependent contextual memory in TN-C-deficient mice using the step-down avoidance paradigm. We further show that a fragment of TN-C containing the fibronectin type-III repeats 6-8 (FN6-8), but not a fragment containing repeats 3-5, bound to pyramidal and granule cell somata in the hippocampal formation of C57BL/6J mice and repelled axons of pyramidal neurons when presented as a border in vitro. Injection of the FN6-8 fragment into the hippocampus inhibited retention of memory in the step-down paradigm and reduced levels of long-term potentiation in the CA1 region of the hippocampus. In summary, our data show that TN-C is involved in hippocampus-dependent contextual memory and synaptic plasticity and identify the FN6-8 domain as one of molecular determinants mediating these functions.

Oxidative stress in a model of toxic demyelination in rat brain: the effect of piracetam and vinpocetine.

PubMed

Abdel-Salam, Omar M E; Khadrawy, Yasser A; Salem, Neveen A; Sleem, Amany A

2011-06-01

We studied the role of oxidative stress and the effect of vinpocetine (1.5, 3 or 6 mg/kg) and piracetam (150 or 300 mg/kg) in acute demyelination of the rat brain following intracerebral injection of ethidium bromide (10 μl of 0.1%). ethidium bromide caused (1) increased malondialdehyde (MDA) in cortex, hippocampus and striatum; (2) decreased total antioxidant capacity (TAC) in cortex, hippocampus and striatum; (3) decreased reduced glutathione (GSH) in cortex and hippocampus (4); increased serum nitric oxide and (5) increased striatal (but not cortical or hippocampal) acetylcholinesterase (AChE) activity. MDA decreased in striatum and cortex by the lower doses of vinpocetine or piracetam but increased in cortex and hippocampus and in cortex, hypothalamus and striatum by the higher dose of vinpocetine or piracetam, respectively along with decreased TAC. GSH increased by the higher dose of piracetam and by vinpocetine which also decreased serum nitric oxide. Vinpocetine and piracetam displayed variable effects on regional AChE activity.

Age-related spatial learning impairment is unrelated to spinophilin immunoreactive spine number and protein levels in rat hippocampus.

PubMed

Calhoun, Michael E; Fletcher, Bonnie R; Yi, Stella; Zentko, Diana C; Gallagher, Michela; Rapp, Peter R

2008-08-01

Age-related impairments in hippocampus-dependent learning and memory tasks are not associated with a loss of hippocampal neurons, but may be related to alterations in synaptic integrity. Here we used stereological techniques to estimate spine number in hippocampal subfields using immunostaining for the spine-associated protein, spinophilin, as a marker. Quantification of the immunoreactive profiles was performed using the optical disector/fractionator technique. Aging was associated with a modest increase in spine number in the molecular layer of the dentate gyrus and CA1 stratum lacunosum-moleculare. By comparison, spinophilin protein levels in the hippocampus, measured by Western blot analysis, failed to differ as a function of age. Neither the morphological nor the protein level data were correlated with spatial learning ability across individual aged rats. The results extend current evidence on synaptic integrity in the aged brain, indicating that a substantial loss of dendritic spines and spinophilin protein in the hippocampus are unlikely to contribute to age-related impairment in spatial learning.

Human cortical–hippocampal dialogue in wake and slow-wave sleep

PubMed Central

Mitra, Anish; Hacker, Carl D.; Pahwa, Mrinal; Tagliazucchi, Enzo; Laufs, Helmut; Leuthardt, Eric C.; Raichle, Marcus E.

2016-01-01

Declarative memory consolidation is hypothesized to require a two-stage, reciprocal cortical–hippocampal dialogue. According to this model, higher frequency signals convey information from the cortex to hippocampus during wakefulness, but in the reverse direction during slow-wave sleep (SWS). Conversely, lower-frequency activity propagates from the information “receiver” to the “sender” to coordinate the timing of information transfer. Reversal of sender/receiver roles across wake and SWS implies that higher- and lower-frequency signaling should reverse direction between the cortex and hippocampus. However, direct evidence of such a reversal has been lacking in humans. Here, we use human resting-state fMRI and electrocorticography to demonstrate that δ-band activity and infraslow activity propagate in opposite directions between the hippocampus and cerebral cortex. Moreover, both δ activity and infraslow activity reverse propagation directions between the hippocampus and cerebral cortex across wake and SWS. These findings provide direct evidence for state-dependent reversals in human cortical–hippocampal communication. PMID:27791089

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

PubMed Central

Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

2016-01-01

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409

β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

PubMed Central

Mander, Bryce A.; Marks, Shawn M.; Vogel, Jacob W.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Ancoli-Israel, Sonia; Jagust, William J.; Walker, Matthew P.

2015-01-01

Independent evidence associates β-amyloid pathology with both NREM sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here, we show that β-amyloid burden within medial prefrontal cortex (mPFC) is significantly correlated with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation is not direct, but instead, statistically depends on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a novel mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly. PMID:26030850

Extracellular metabolites in the cortex and hippocampus of epileptic patients.

PubMed

Cavus, Idil; Kasoff, Willard S; Cassaday, Michael P; Jacob, Ralph; Gueorguieva, Ralitza; Sherwin, Robert S; Krystal, John H; Spencer, Dennis D; Abi-Saab, Walid M

2005-02-01

Interictal brain energy metabolism and glutamate-glutamine cycling are impaired in epilepsy and may contribute to seizure generation. We used the zero-flow microdialysis method to measure the extracellular levels of glutamate, glutamine, and the major energy substrates glucose and lactate in the epileptogenic and the nonepileptogenic cortex and hippocampus of 38 awake epileptic patients during the interictal period. Depth electrodes attached to microdialysis probes were used to identify the epileptogenic and the nonepileptogenic sites. The epileptogenic hippocampus had surprisingly high basal glutamate levels, low glutamine/glutamate ratio, high lactate levels, and indication for poor glucose utilization. The epileptogenic cortex had only marginally increased glutamate levels. We propose that interictal energetic deficiency in the epileptogenic hippocampus could contribute to impaired glutamate reuptake and glutamate-glutamine cycling, resulting in persistently increased extracellular glutamate, glial and neuronal toxicity, increased lactate production together with poor lactate and glucose utilization, and ultimately worsening energy metabolism. Our data suggest that a different neurometabolic process underlies the neocortical epilepsies.

Episodic Memory and Beyond: The Hippocampus and Neocortex in Transformation.

PubMed

Moscovitch, Morris; Cabeza, Roberto; Winocur, Gordon; Nadel, Lynn

2016-01-01

The last decade has seen dramatic technological and conceptual changes in research on episodic memory and the brain. New technologies, and increased use of more naturalistic observations, have enabled investigators to delve deeply into the structures that mediate episodic memory, particularly the hippocampus, and to track functional and structural interactions among brain regions that support it. Conceptually, episodic memory is increasingly being viewed as subject to lifelong transformations that are reflected in the neural substrates that mediate it. In keeping with this dynamic perspective, research on episodic memory (and the hippocampus) has infiltrated domains, from perception to language and from empathy to problem solving, that were once considered outside its boundaries. Using the component process model as a framework, and focusing on the hippocampus, its subfields, and specialization along its longitudinal axis, along with its interaction with other brain regions, we consider these new developments and their implications for the organization of episodic memory and its contribution to functions in other domains.

Neural basis of the cognitive map: path integration does not require hippocampus or entorhinal cortex.

PubMed

Shrager, Yael; Kirwan, C Brock; Squire, Larry R

2008-08-19

The hippocampus and entorhinal cortex have been linked to both memory functions and to spatial cognition, but it has been unclear how these ideas relate to each other. An important part of spatial cognition is the ability to keep track of a reference location using self-motion cues (sometimes referred to as path integration), and it has been suggested that the hippocampus or entorhinal cortex is essential for this ability. Patients with hippocampal lesions or larger lesions that also included entorhinal cortex were led on paths while blindfolded (up to 15 m in length) and were asked to actively maintain the path in mind. Patients pointed to and estimated their distance from the start location as accurately as controls. A rotation condition confirmed that performance was based on self-motion cues. When demands on long-term memory were increased, patients were impaired. Thus, in humans, the hippocampus and entorhinal cortex are not essential for path integration.

Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local–global reference frames

PubMed Central

Knierim, James J.; Neunuebel, Joshua P.; Deshmukh, Sachin S.

2014-01-01

The hippocampus receives its major cortical input from the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC). It is commonly believed that the MEC provides spatial input to the hippocampus, whereas the LEC provides non-spatial input. We review new data which suggest that this simple dichotomy between ‘where’ versus ‘what’ needs revision. We propose a refinement of this model, which is more complex than the simple spatial–non-spatial dichotomy. MEC is proposed to be involved in path integration computations based on a global frame of reference, primarily using internally generated, self-motion cues and external input about environmental boundaries and scenes; it provides the hippocampus with a coordinate system that underlies the spatial context of an experience. LEC is proposed to process information about individual items and locations based on a local frame of reference, primarily using external sensory input; it provides the hippocampus with information about the content of an experience. PMID:24366146

The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.

PubMed

Pavković, Željko; Milanović, Desanka; Ruždijić, Sabera; Kanazir, Selma; Pešić, Vesna

2018-06-01

The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca 2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure. © 2018 John Wiley & Sons Ltd.

Fluoride and Arsenic Exposure Impairs Learning and Memory and Decreases mGluR5 Expression in the Hippocampus and Cortex in Rats

PubMed Central

Jiang, Shoufang; Su, Jing; Yao, Sanqiao; Zhang, Yanshu; Cao, Fuyuan; Wang, Fei; Wang, Huihui; Li, Jun; Xi, Shuhua

2014-01-01

Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and mGluR5 expression in cortex and hippocampus. PMID:24759735

The hippocampus and related neocortical structures in memory transformation.

PubMed

Sekeres, Melanie J; Winocur, Gordon; Moscovitch, Morris

2018-05-04

Episodic memories are multifaceted and malleable, capable of being transformed with time and experience at both the neural level and psychological level. At the neural level, episodic memories are transformed from being dependent on the hippocampus to becoming represented in neocortical structures, such as the medial prefrontal cortex (mPFC), and back again, while at the psychological level, detailed, perceptually rich memories, are transformed to ones retaining only the gist of an experience or a schema related to it. Trace Transformation Theory (TTT) initially proposed that neural and psychological transformations are linked and proceed in tandem. Building on recent studies on the neurobiology of memory transformation in rodents and on the organization of the hippocampus and its functional cortical connectivity in humans, we present an updated version of TTT that is more precise and detailed with respect to the dynamic processes and structures implicated in memory transformation. At the heart of the updated TTT lies the long axis of the hippocampus whose functional differentiation and connectivity to neocortex make it a hub for memory formation and transformation. The posterior hippocampus, connected to perceptual and spatial representational systems in posterior neocortex, supports fine, perceptually rich, local details of memories; the anterior hippocampus, connected to conceptual systems in anterior neocortex, supports coarse, global representations that constitute the gist of a memory. Notable among the anterior structures is the medial prefrontal cortex which supports representation of schemas that code for common aspects of memories across different episodes. Linking the aHPC with mPFC is the entorhinal cortex (EC) which conveys information needed for the interaction/translation between gist and schemas. Thus, the long axis of the hippocampus, mPFC and EC provide the representational gradient, from fine to coarse and from perceptual to conceptual, that can implement processes implicated in memory transformation. Each of these representations of an episodic memory can co-exist with one another and be in dynamic flux as they interact with one another throughout the memory's lifetime, going from detailed to schematic and possibly back again, all mediated by corresponding changes in neural representation. Copyright © 2018 Elsevier B.V. All rights reserved.

Memory on time

PubMed Central

Eichenbaum, Howard

2013-01-01

Considerable recent work has shown that the hippocampus is critical for remembering the order of events in distinct experiences, a defining feature of episodic memory. Correspondingly, hippocampal neuronal activity can ‘replay’ sequential events in memories and hippocampal neuronal ensembles represent a gradually changing temporal context signal. Most strikingly, single hippocampal neurons – called time cells – encode moments in temporally structured experiences much as the well-known place cells encode locations in spatially structured experiences. These observations bridge largely disconnected literatures on the role of the hippocampus in episodic memory and spatial mapping, and suggest that the fundamental function of the hippocampus is to establish spatio-temporal frameworks for organizing memories. PMID:23318095

Fish, fans and hydroids: host species of pygmy seahorses

PubMed Central

Reijnen, Bastian T.; van der Meij, Sancia E.T.; van Ofwegen, Leen P.

2011-01-01

Abstract An overview of the octocoral and hydrozoan host species of pygmy seahorses is provided based on literature records and recently collected field data for Hippocampus bargibanti, Hippocampus denise and Hippocampus pontohi. Seven new associations are recognized and an overview of the so far documented host species is given. A detailed re-examination of octocoral type material and a review of the taxonomic history of the alcyonacean genera Annella (Subergorgiidae) and Muricella (Acanthogorgiidae) are included as baseline for future revisions. The host specificity and colour morphs of pygmy seahorses are discussed, as well as the reliability of (previous) identifications and conservation issues. PMID:21747677

An assessment of West African seahorses in fisheries catch and trade.

PubMed

Cisneros-Montemayor, A M; West, K; Boiro, I S; Vincent, A C J

2016-02-01

This study provides the first assessment of a heavily traded West African seahorse species, Hippocampus algiricus, and the first information on short-snouted seahorse Hippocampus hippocampus biology in Africa. A total of 219 seahorses were sampled from fisher catch in Senegal and The Gambia, with estimated height at reproductive activity for H. algiricus (161 mm) larger than mean ± S.D. catch height (150 ± 31 mm). Catch composition, height at reproductive activity and potential biases in fishery retention are discussed with regard to the current Convention on International Trade of Endangered Species (CITES) guidelines. © 2015 The Fisheries Society of the British Isles.

Odor-mediated taste learning requires dorsal hippocampus, but not basolateral amygdala activity

PubMed Central

Wheeler, Daniel S.; Chang, Stephen E.; Holland, Peter C.

2013-01-01

Mediated learning is a unique cognitive phenomenon in which mental representations of physically absent stimuli enter into associations with directly-activated representations of physically present stimuli. Three experiments investigated the functional physiology of mediated learning involving the use of odor-taste associations. In Experiments 1a and 1b, basolateral amygdala lesions failed to attenuate mediated taste aversion learning. In Experiment 2, dorsal hippocampus inactivation impaired mediated learning, but left direct learning intact. Considered with past studies, the results implicate the dorsal hippocampus in mediated learning generally, and suggest a limit on the importance of the basolateral amygdala. PMID:23274135

DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.

EPA Science Inventory

GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreact...

Adult onset-hypothyroidism increases response latency and long-term potentiation (LTP) in rat hippocampus

EPA Science Inventory

Thyroid hormones (TH) influence central nervous system (CNS) function during both development and in adulthood. The hippocampus is critical for some types of learning and memory and is particularly sensitive to thyroid hormone deficiency. Hypothyroidism in adulthood has been ass...

Stress Effects on the Hippocampus: A Critical Review

ERIC Educational Resources Information Center

Kim, Eun Joo; Pellman, Blake; Kim, Jeansok J.

2015-01-01

Uncontrollable stress has been recognized to influence the hippocampus at various levels of analysis. Behaviorally, human and animal studies have found that stress generally impairs various hippocampal-dependent memory tasks. Neurally, animal studies have revealed that stress alters ensuing synaptic plasticity and firing properties of hippocampal…

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS.

EPA Science Inventory

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT HIPPOCAMPUS. ME Gilbert1, ME Kelly2, S. Salant3, T Shafer1, J Goodman3 1Neurotoxicology Div, US EPA, RTP, NC, 27711, 2Children's Hospital, Philadelphia, PA, 19104, 3Helen Hayes Hospital, Haverstraw, NY, 10993.
...

[The effects of methionine and choline on the expression levels of CaMKII and CREB mRNA and proteins in rats exposed to lead].

PubMed

Feng, Chang; Fan, Guang-qin; Wu, Feng-yun; Lin, Fen; Li, Yan-shu; Chen, Ying

2012-07-01

To study the effects of methionine and choline on the expression levels of CaMKII and CREB mRNA and proteins in hippocampus of rats exposed to lead. Male SD rats were divided into five groups. (1) control group, (2) group exposed to lead+2 by drinking water with 0.40 g/L lead acetate, (3) group exposed to methionine and choline (1:1, 400 mg/kg), (4) group exposed to 0.40 g/L lead acetate plus methionine and choline (1:1, 100 mg/kg), (5) group exposed to 0.40 g/L lead acetate plus methionine and choline (1:1, 400 mg/kg). In 8 weeks after exposure, all rats were killed. Then CREB mRNA and CaMK II mRNA expression levels in hippocampus were detected by real-time PCR, CREB and CaMK II protein expression levels in hippocampus were measured by western blot assay. The expression levels (0.743 ± 0.185 and 0.729 ± 0.199) of CaMKII mRNA and CREB mRNA in the hippocampus of lead group were significantly lower than those (0.950 ± 0.238 and 0.901 ± 0.232) of control group (P < 0.05), also the expression levels (0.271 ± 0.045 and 0.212 ± 0.058) of CREB protein and pCREB protein in the hippocampus of lead group were significantly lower than those (0.319 ± 0.058 and 0.506 ± 0.125) of control group (P < 0.05). The expression levels (1.014 ± 0.210 and 1.126 ± 0.379) of CaMKII mRNA and the expression levels (1.029 ± 0.335 and 0.932 ± 0.251) of CREB mRNA in the hippocampus of 2 groups exposed to lead acetate plus methionine and choline were significantly higher than those of lead group (P < 0.05). The expression levels (0.407 ± 0.951 and 0.563 ± 0.178) of CREB protein and pCREB protein in the hippocampus of group exposed to lead acetate plus 400 mg/kg methionine and choline were significantly higher than those of lead group (P < 0.05). Methionine and choline could decrease the inhibition effects of lead on the expression of CaMKII and CREB mRNA or CREB and pCREB proteins in the hippocampus of rats.

Hippocampal activation during retrieval of spatial context from episodic and semantic memory.

PubMed

Hoscheidt, Siobhan M; Nadel, Lynn; Payne, Jessica; Ryan, Lee

2010-10-15

The hippocampus, a region implicated in the processing of spatial information and episodic memory, is central to the debate concerning the relationship between episodic and semantic memory. Studies of medial temporal lobe amnesic patients provide evidence that the hippocampus is critical for the retrieval of episodic but not semantic memory. On the other hand, recent neuroimaging studies of intact individuals report hippocampal activation during retrieval of both autobiographical memories and semantic information that includes historical facts, famous faces, and categorical information, suggesting that episodic and semantic memory may engage the hippocampus during memory retrieval in similar ways. Few studies have matched episodic and semantic tasks for the degree to which they include spatial content, even though spatial content may be what drives hippocampal activation during semantic retrieval. To examine this issue, we conducted a functional magnetic resonance imaging (fMRI) study in which retrieval of spatial and nonspatial information was compared during an episodic and semantic recognition task. Results show that the hippocampus (1) participates preferentially in the retrieval of episodic memories; (2) is also engaged by retrieval of semantic memories, particularly those that include spatial information. These data suggest that sharp dissociations between episodic and semantic memory may be overly simplistic and that the hippocampus plays a role in the retrieval of spatial content whether drawn from a memory of one's own life experiences or real-world semantic knowledge. Published by Elsevier B.V.

Acquisition of contextual discrimination involves the appearance of a RAS-GRF1/p38 mitogen-activated protein (MAP) kinase-mediated signaling pathway that promotes long term potentiation (LTP).

PubMed

Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A

2013-07-26

RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway.

Effect of acute alarm odor exposure and biological sex on generalized avoidance and glutamatergic signaling in the hippocampus of Wistar rats.

PubMed

Homiack, Damek; O'Cinneide, Emma; Hajmurad, Sema; Dohanich, Gary P; Schrader, Laura A

2018-06-19

Post-traumatic stress disorder (PTSD) is characterized by the development of paradoxical memory disturbances including intrusive memories and amnesia for specific details of the traumatic experience. Despite evidence that women are at higher risk to develop PTSD, most animal research has focused on the processes by which male rodents develop adaptive fear memory. As such, the mechanisms contributing to sex differences in the development of PTSD-like memory disturbances are poorly understood. In this investigation, we exposed adult male and female Wistar rats to the synthetic alarm odor 2,4,5-trimethylthiazole (TMT) to assess development of generalized fear behavior and rapid modulation of glutamate uptake and signaling cascades associated with hippocampus-dependent long-term memory. We report that female Wistar rats exposed to alarm odor exhibit context discrimination impairments relative to TMT-exposed male rats, suggesting the intriguing possibility that females are at greater risk in developing generalized fear memories. Mechanistically, alarm odor exposure rapidly modulated signaling cascades consistent with activation of the CREB shut-off cascade in the male, but not the female hippocampus. Moreover, TMT exposure dampened glutamate uptake and affected expression of the glutamate transporter, GLT-1 in the hippocampus. Taken together, these results provide evidence for rapid sex-dependent modulation of CREB signaling in the hippocampus by alarm odor exposure which may contribute to the development of generalized fear.

The effects of 30 mT electromagnetic fields on hippocampus cells of rats

PubMed Central

Teimori, Farzaneh; Khaki, Amir A.; Rajabzadeh, Asghar; Roshangar, Leila

2016-01-01

Background: Despite the use of electromagnetic waves in the treatment of some acute and chronic diseases, application of these waves in everyday life has created several problems for humans, especially the nerve system. In this study, the effects of 30mT electromagnetic fields (EMFs) on the hippocampus is investigated. Methods: Twenty-four 5-month Wistar rats weighing 150–200 g were divided into two groups. The experimental group rats were under the influence of an EMF at an intensity of 3 mT for approximately 4 hours a day (from 8 AM to 12 PM) during 10 weeks. After the hippocampus was removed, thin slides were prepared for transmission electron microscope (TEM) to study the ultrastructural tissue. Cell death detection POD kits were used to determine the apoptosis rate. Results: The results of the TEM showed that, in the hippocampus of the experimental group, in comparison to the control group, there was a substantial shift; even intracellular organelles such as the mitochondria were morphologically abnormal and uncertain. The number of apoptotic cells in the exposed group compared to the control group showed significant changes. Conclusions: Similar to numerous studies that have reported the effects of EMFs on nerves system, it was also confirmed in this lecture. Hence, the hippocampus which is important in regulating emotions, behavior, motivation, and memory functions, may be impaired by the negative impacts of EMFs. PMID:27453795

Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls.

PubMed

Janiri, Delfina; Sani, Gabriele; Rossi, Pietro De; Piras, Fabrizio; Iorio, Mariangela; Banaj, Nerisa; Giuseppin, Giulia; Spinazzola, Edoardo; Maggiora, Matteo; Ambrosi, Elisa; Simonetti, Alessio; Spalletta, Gianfranco

2017-08-01

Volumetric studies on deep gray matter structures in bipolar disorder (BP) have reported contrasting results. Childhood trauma, a relevant environmental stressor for BP, could account for the variability of the results, modulating differences in the amygdala and hippocampus in patients with BP compared with healthy controls (HC). Our study aimed to test this hypothesis. We assessed 105 outpatients, diagnosed with bipolar disorder type I (BP-I) or bipolar disorder type II (BP-II) according to DSM-IV-TR criteria, and 113 HC subjects. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). High-resolution magnetic resonance imaging was performed on all subjects and volumes of the amygdala, hippocampus, nucleus accumbens, caudate, pallidum, putamen, and thalamus were measured using FreeSurfer. Patients with BP showed a global reduction of deep gray matter volumes compared to HCs. However, childhood trauma modulated the impact of the diagnosis specifically on the amygdala and hippocampus. Childhood trauma was associated with bilateral decreased volumes in HCs and increased volumes in patients with BP. The results suggest that childhood trauma may have a different effect in health and disease on volumes of gray matter in the amygdala and hippocampus, which are brain areas specifically involved in response to stress and emotion processing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A synthesis of European seahorse taxonomy, population structure, and habitat use as a basis for assessment, monitoring and conservation.

PubMed

Woodall, Lucy C; Otero-Ferrer, Francisco; Correia, Miguel; Curtis, Janelle M R; Garrick-Maidment, Neil; Shaw, Paul W; Koldewey, Heather J

2018-01-01

Accurate taxonomy, population demography, and habitat descriptors inform species threat assessments and the design of effective conservation measures. Here we combine published studies with new genetic, morphological and habitat data that were collected from seahorse populations located along the European and North African coastlines to help inform management decisions for European seahorses. This study confirms the presence of only two native seahorse species ( Hippocampus guttulatus and H. hippocampus ) across Europe, with sporadic occurrence of non-native seahorse species in European waters. For the two native species, our findings demonstrate that highly variable morphological characteristics, such as size and presence or number of cirri, are unreliable for distinguishing species. Both species exhibit sex dimorphism with females being significantly larger. Across its range, H. guttulatus were larger and found at higher densities in cooler waters, and individuals in the Black Sea were significantly smaller than in other populations. H. hippocampus were significantly larger in Senegal. Hippocampus guttulatus tends to have higher density populations than H. hippocampus when they occur sympatrically. Although these species are often associated with seagrass beds, data show both species inhabit a wide variety of shallow habitats and use a mixture of holdfasts. We suggest an international mosaic of protected areas focused on multiple habitat types as the first step to successful assessment, monitoring and conservation management of these Data Deficient species.

Independent Neuronal Representation of Facial and Vocal Identity in the Monkey Hippocampus and Inferotemporal Cortex.

PubMed

Sliwa, Julia; Planté, Aurélie; Duhamel, Jean-René; Wirth, Sylvia

2016-03-01

Social interactions make up to a large extent the prime material of episodic memories. We therefore asked how social signals are coded by neurons in the hippocampus. Human hippocampus is home to neurons representing familiar individuals in an abstract and invariant manner ( Quian Quiroga et al. 2009). In contradistinction, activity of rat hippocampal cells is only weakly altered by the presence of other rats ( von Heimendahl et al. 2012; Zynyuk et al. 2012). We probed the activity of monkey hippocampal neurons to faces and voices of familiar and unfamiliar individuals (monkeys and humans). Thirty-one percent of neurons recorded without prescreening responded to faces or to voices. Yet responses to faces were more informative about individuals than responses to voices and neuronal responses to facial and vocal identities were not correlated, indicating that in our sample identity information was not conveyed in an invariant manner like in human neurons. Overall, responses displayed by monkey hippocampal neurons were similar to the ones of neurons recorded simultaneously in inferotemporal cortex, whose role in face perception is established. These results demonstrate that the monkey hippocampus participates in the read-out of social information contrary to the rat hippocampus, but possibly lack an explicit conceptual coding of as found in humans. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The neural substrates of deliberative decision making: contrasting effects of hippocampus lesions on performance and vicarious trial-and-error behavior in a spatial memory task and a visual discrimination task

PubMed Central

Bett, David; Allison, Elizabeth; Murdoch, Lauren H.; Kaefer, Karola; Wood, Emma R.; Dudchenko, Paul A.

2012-01-01

Vicarious trial-and-errors (VTEs) are back-and-forth movements of the head exhibited by rodents and other animals when faced with a decision. These behaviors have recently been associated with prospective sweeps of hippocampal place cell firing, and thus may reflect a rodent model of deliberative decision-making. The aim of the current study was to test whether the hippocampus is essential for VTEs in a spatial memory task and in a simple visual discrimination (VD) task. We found that lesions of the hippocampus with ibotenic acid produced a significant impairment in the accuracy of choices in a serial spatial reversal (SR) task. In terms of VTEs, whereas sham-lesioned animals engaged in more VTE behavior prior to identifying the location of the reward as opposed to repeated trials after it had been located, the lesioned animals failed to show this difference. In contrast, damage to the hippocampus had no effect on acquisition of a VD or on the VTEs seen in this task. For both lesion and sham-lesion animals, adding an additional choice to the VD increased the number of VTEs and decreased the accuracy of choices. Together, these results suggest that the hippocampus may be specifically involved in VTE behavior during spatial decision making. PMID:23115549

Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

PubMed Central

Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

2011-01-01

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.

PubMed

Sasaki, Keita; Omotuyi, Olaposi Idowu; Ueda, Mutsumi; Shinohara, Kazuyuki; Ueda, Hiroshi

2015-12-04

Structural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice. We successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam. The present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.

Intrahippocampal administration of anandamide increases REM sleep.

PubMed

Rueda-Orozco, Pavel Ernesto; Soria-Gómez, Edgar; Montes-Rodríguez, Corinne Jennifer; Pérez-Morales, Marcel; Prospéro-García, Oscar

2010-04-05

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light-dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep-waking cycle at two points of the light-dark cycle. Our data indicate that the administration of ANA directly into the hippocampus increases REMs in a dose dependent manner during the dark but not during the light phase of the cycle. The increase of REMs was blocked by the CB1 antagonist AM251. This effect was specific for the hippocampus since ANA administrations in the surrounding cortex did not elicit any change in REMs. These results support the idea of a direct relationship between hippocampal activity and sleep mechanisms by means of eCBs. The data presented here show, for the first time that eCBs administered into the hippocampus trigger REMs and support previous studies where chemical stimulation of limbic areas triggered sleep.

Neuromodulation: acetylcholine and memory consolidation.

PubMed

Hasselmo

1999-09-01

Clinical and experimental evidence suggests that hippocampal damage causes more severe disruption of episodic memories if those memories were encoded in the recent rather than the more distant past. This decrease in sensitivity to damage over time might reflect the formation of multiple traces within the hippocampus itself, or the formation of additional associative links in entorhinal and association cortices. Physiological evidence also supports a two-stage model of the encoding process in which the initial encoding occurs during active waking and deeper consolidation occurs via the formation of additional memory traces during quiet waking or slow-wave sleep. In this article I will describe the changes in cholinergic tone within the hippocampus in different stages of the sleep-wake cycle and will propose that these changes modulate different stages of memory formation. In particular, I will suggest that the high levels of acetylcholine that are present during active waking might set the appropriate dynamics for encoding new information in the hippocampus, by partially suppressing excitatory feedback connections and so facilitating encoding without interference from previously stored information. By contrast, the lower levels of acetylcholine that are present during quiet waking and slow-wave sleep might release this suppression and thereby allow a stronger spread of activity within the hippocampus itself and from the hippocampus to the entorhinal cortex, thus facilitating the process of consolidation of separate memory traces.

Ageing introduces a complex pattern of changes in several rat brain transcription factors depending on gender and anatomical localization.

PubMed

Sanguino, Elena; Roglans, Núria; Rodríguez-Calvo, Ricardo; Alegret, Marta; Sánchez, Rosa M; Vázquez-Carrera, Manuel; Laguna, Juan C

2006-04-01

As ageing changes the activity of several transcription factors in the rat cortex, we were interested in determining whether similar changes also appear in the hippocampus of old rats. We determined by electrophoretic gel shift assays the binding activity of nuclear factor kappa B (NFkappaB), activator protein-1 (AP-1), peroxisome proliferator-activated receptor (PPAR), and liver X receptor (LXR) in cortex and hippocampus samples from young (3-month-old), and old (18-month-old) male and female Sprague-Dawley rats. NFkappaB activity increased in old male and female rats, though only in cortex samples, while AP-1 activity decreased only in the cortex and hippocampus of old female animals. LXR activity decreased in all conditions, except in old male cortexes; whereas PPAR activity only decreased in the hippocampus of old female rats. Decreases in AP-1 and PPAR activities restricted to old female rats did not result from an age-related decline in plasma 17beta-estradiol concentration, as their activities did not change in samples obtained from ovariectomized young female rats. Our results indicate that ageing induces a complex pattern of changes in the brain-binding activity of NFkappaB, AP-1, PPAR and LXR, depending on the anatomical origin of the samples (cortex or hippocampus), and the sex of the animals studied.

Relationship between cognition function and hippocampus structure after long-term microwave exposure.

PubMed

Zhao, Li; Peng, Rui Yun; Wang, Shui Ming; Wang, Li Feng; Gao, Ya Bing; Dong, Ji; Li, Xiang; Su, Zhen Tao

2012-04-01

To analyze the effects of long-term microwave exposure on hippocampal structure and function in the rat. Experiments were performed on 184 male Wistar rats (three exposure groups and a sham group). Microwaves were applied daily for 6 min over 1 month at average power densities of 2.5, 5, and 10 mW/cm2. Learning and memory abilities were assessed by Morris water maze. High performance liquid chromatography was used to detect neurotransmitter concentrations in the hippocampus. Hippocampal structures were observed by histopathological analysis. Following long-term microwave exposure there was a significant decrease in learning and memory activity in the 7 d, 14 d, and 1 m in all three microwave exposure groups. Neurotransmitter concentrations of four amino acids (glutamate, aspartic acid, glycine, and gamma-aminobutyric acid) in hippocampus were increased in the 2.5 and 5 mW/cm2 groups and decreased in the 10 mW/cm2 group. There was evidence of neuronal degeneration and enlarged perivascular spaces in the hippocampus in the microwave exposure groups. Further, mitochondria became swollen and cristae were disordered. The rough endoplasmic reticulum exhibited sacculated distension and there was a decrease in the quantity of synaptic vesicles. These data suggest that the hippocampus can be injured by long-term microwave exposure, which might result in impairment of cognitive function due to neurotransmitter disruption.

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients.

PubMed

Stewart, Christopher C; Griffith, H Randall; Okonkwo, Ozioma C; Martin, Roy C; Knowlton, Robert K; Richardson, Elizabeth J; Hermann, Bruce P; Seidenberg, Michael

2009-02-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats. Comparison of lateral fluid percussion and cortical impact models.

PubMed

Hicks, R R; Baldwin, S A; Scheff, S W

1997-01-01

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical techniques for alterations in the serum protein, IgG, and the cytoskeletal protein, microtubule-associated protein 2 (MAP2). Both models induced profound alterations in these proteins in the ipsilateral cortex and hippocampus compared to sham-injured controls. Following an injury of moderate severity, the CI injury resulted in greater IgG extravasation in the cortex and hippocampus than the FP injury. Conversely, after a mild injury, IgG extravasation in the hippocampus was greater for FP than CI. All of the animals in the CI group and most of the FP group showed a loss of MAP2 in the hippocampus. The specific subregions within the cortex and hippocampus that were affected by the injury varied between models, despite having identical impact sites. These data demonstrate that there are both similarities and differences between a CI and FP injury on vascular and neuronal cystoskeletal integrity, which should be considered when utilizing these animal models to study selected features of human head injury.

The Role of Anterior Nuclei of the Thalamus: A Subcortical Gate in Memory Processing: An Intracerebral Recording Study.

PubMed

Štillová, Klára; Jurák, Pavel; Chládek, Jan; Chrastina, Jan; Halámek, Josef; Bočková, Martina; Goldemundová, Sabina; Říha, Ivo; Rektor, Ivan

2015-01-01

To study the involvement of the anterior nuclei of the thalamus (ANT) as compared to the involvement of the hippocampus in the processes of encoding and recognition during visual and verbal memory tasks. We studied intracerebral recordings in patients with pharmacoresistent epilepsy who underwent deep brain stimulation (DBS) of the ANT with depth electrodes implanted bilaterally in the ANT and compared the results with epilepsy surgery candidates with depth electrodes implanted bilaterally in the hippocampus. We recorded the event-related potentials (ERPs) elicited by the visual and verbal memory encoding and recognition tasks. P300-like potentials were recorded in the hippocampus by visual and verbal memory encoding and recognition tasks and in the ANT by the visual encoding and visual and verbal recognition tasks. No significant ERPs were recorded during the verbal encoding task in the ANT. In the visual and verbal recognition tasks, the P300-like potentials in the ANT preceded the P300-like potentials in the hippocampus. The ANT is a structure in the memory pathway that processes memory information before the hippocampus. We suggest that the ANT has a specific role in memory processes, especially memory recognition, and that memory disturbance should be considered in patients with ANT-DBS and in patients with ANT lesions. ANT is well positioned to serve as a subcortical gate for memory processing in cortical structures.

Hippocampus and amygdala volumes in parents of children with autistic disorder.

PubMed

Rojas, Donald C; Smith, J Allegra; Benkers, Tara L; Camou, Suzanne L; Reite, Martin L; Rogers, Sally J

2004-11-01

Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.

Inactivation of the Nucleus Reuniens/Rhomboid Causes a Delay-dependent Impairment of Spatial Working Memory

PubMed Central

Layfield, Dylan M.; Patel, Monica; Hallock, Henry; Griffin, Amy

2015-01-01

Inactivation of the rodent medial prefrontal cortex (mPFC) and hippocampus or disconnection of the hippocampus from the mPFC produces deficits in spatial working memory tasks. Previous studies have shown that delay length determines the extent to which mPFC and hippocampus functionally interact, with both structures being necessary for tasks with longer delays and either structure being sufficient for tasks with shorter delays. In addition, inactivation of the nucleus reuniens (Re) / rhomboid nucleus (Rh) of the thalamus, which has bidirectional connections with the mPFC and hippocampus, also produces deficits in these tasks. However, it is unknown how delay duration relates to the function of Re/Rh. If Re/Rh are critical in modulating mPFC-hippocampus interactions, inactivation of the RE/Rh should produce a delay-dependent impairment in spatial working memory performance. To investigate this question, groups of rats were trained on one of three different spatial working memory tasks: continuous alternation (CA), delayed alternation with a five-second delay (DA5), or with a thirty-second delay (DA30). The Re/Rh were inactivated with muscimol infusions prior to testing. The results demonstrate that inactivation of RE/Rh produces a deficit only on the two DA tasks, supporting the notion that the Re/Rh is a critical orchestrator of mPFC-HC interactions. PMID:26391450

Retrieval of Inhibitory Avoidance Memory Induces Differential Transcription of arc in Striatum, Hippocampus, and Amygdala.

PubMed

González-Salinas, Sofía; Medina, Andrea C; Alvarado-Ortiz, Eduardo; Antaramian, Anaid; Quirarte, Gina L; Prado-Alcalá, Roberto A

2018-07-01

Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. We found that arc expression in the striatum increased 30 min after retrieval while no changes were observed in zif268 in this region. Expression of arc and zif268 also increased in the dorsal hippocampus but the changes were attributed to context re-exposure. Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

[Impairment of spatial learning and memory and changes of oxidative stress in hippocampus from Type 1 diabetic mice].

PubMed

Wang, Chun; Lü, Gaoyou; Li, Yan; Zhao, Shidi; Huang, Li

2018-05-28

To investigate the relevance between spatial learning and memory impairment and the changes of inducible nitric oxide synthase (iNOS) activity, superoxide dismutase (SOD) activity and malondiadehyde (MDA) content in hippocampus from Type 1 diabetic mice.
 Methods: Sixty male mice were randomly assigned into a control group (NC group, 20 mice) and a Type 1 diabetic group (DM group, 40 mice). Type 1 diabetic mouse models were established by a large dose intraperitoneal injection of streptozotocin (100 mg/kg). The spatial learning and memory abilities of mice were assessed by Morris water maze (MWM) test. After MWM test, we chose 20 mice (diabetic encephalopathy mice) with the worst spatial learning and memory abilities from diabetic model group, and detected the iNOS activity, SOD activity and MDA content in hippocampus in both groups.
 Results: Compared with the NC group, the escape latency was significantly extended and platform crossings were significantly declined in diabetic mice (P<0.01). Furthermore, the activity of iNOS and the content of MDA were markedly increased, and the activity of SOD was significantly decreased in hippocampus of diabetic encephalopathy mice (P<0.01).
 Conclusion: The established Type 1 diabetic mice show symptoms of cognitive dysfunction, which might be related to the increase of oxidative stress in hippocampus.

What relates newspaper, definite, and clothing? An article describing deficits in convergent problem solving and creativity following hippocampal damage.

PubMed

Warren, David E; Kurczek, Jake; Duff, Melissa C

2016-07-01

Creativity relies on a diverse set of cognitive processes associated with distinct neural correlates, and one important aspect of creativity, divergent thinking, has been associated with the hippocampus. However, hippocampal contributions to another important aspect of creativity, convergent problem solving, have not been investigated. We tested the necessity of hippocampus for convergent problem solving using a neuropsychological method. Participants with amnesia due to hippocampal damage (N = 5) and healthy normal comparison participants (N = 5) were tested using a task that promoted solutions based on existing knowledge (Bowden and Jung-Beeman, 2003). During each trial, participants were given a list of three words (e.g., fly, man, place) and asked to respond with a word that could be combined with each of the three words (e.g., fire). The amnesic group produced significantly fewer correct responses than the healthy comparison group. These findings indicate that the hippocampus is necessary for normal convergent problem solving and that changes in the status of the hippocampus should affect convergent problem solving in the context of creative problem-solving across short intervals. This proposed contribution of the hippocampus to convergent problem solving is consistent with an expanded perspective on hippocampal function that acknowledges its role in cognitive processes beyond declarative memory. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Acquisition of Contextual Discrimination Involves the Appearance of a RAS-GRF1/p38 Mitogen-activated Protein (MAP) Kinase-mediated Signaling Pathway That Promotes Long Term Potentiation (LTP)*

PubMed Central

Jin, Shan-Xue; Arai, Junko; Tian, Xuejun; Kumar-Singh, Rajendra; Feig, Larry A.

2013-01-01

RAS-GRF1 is a guanine nucleotide exchange factor with the ability to activate RAS and RAC GTPases in response to elevated calcium levels. We previously showed that beginning at 1 month of age, RAS-GRF1 mediates NMDA-type glutamate receptor (NMDAR)-induction of long term depression in the CA1 region of the hippocampus of mice. Here we show that beginning at 2 months of age, when mice first acquire the ability to discriminate between closely related contexts, RAS-GRF1 begins to contribute to the induction of long term potentiation (LTP) in the CA1 hippocampus by mediating the action of calcium-permeable, AMPA-type glutamate receptors (CP-AMPARs). Surprisingly, LTP induction by CP-AMPARs through RAS-GRF1 occurs via activation of p38 MAP kinase rather than ERK MAP kinase, which has more frequently been linked to LTP. Moreover, contextual discrimination is blocked by knockdown of Ras-Grf1 expression specifically in the CA1 hippocampus, infusion of a p38 MAP kinase inhibitor into the CA1 hippocampus, or the injection of an inhibitor of CP-AMPARs. These findings implicate the CA1 hippocampus in the developmentally dependent capacity to distinguish closely related contexts through the appearance of a novel LTP-supporting signaling pathway. PMID:23766509

Necroptosis Resumes Apoptosis in Hippocampus but Not in Frontal Cortex.

PubMed

Nikseresht, Sara; Khodagholi, Fariba; Dargahi, Leila; Ahmadiani, Abolhassan

2017-12-01

Cell death subsequent to or concurrent with neuroinflammation results in some damages like neuron loss and spatial memory impairment. In this study, we demonstrated the temporal pattern of neuroinflammation, necroptotic, and apoptotic cell deaths in hippocampus and frontal cortex following intracerebroventricular administration of lipopolysaccharide (LPS). We evaluated receptor interacting protein kinase 1 (RIP1), RIP3, and two related metabolic enzymes including glutamate-ammonia ligase (GLUL) and glutamate dehydrogenase (GLUD) as necroptosis factors. Apoptosis pathway, antioxidant status and inflammatory cytokines were also assessed. Based on the probable role of these brain regions in working memory performance, spontaneous alternation was evaluated through the Y-maze apparatus. RIP1, RIP3, and then GLUL and GLUD, as well as apoptosis markers, inflammatory regulators, and antioxidant defense demonstrated different time-dependent patterns in hippocampus and frontal cortex. Interestingly, in hippocampus but not in frontal cortex, necroptosis resumed apoptosis. Our results in behavioral section revealed that neuroinflammation along with apoptosis and necroptosis pathways could lead to reversible short-term memory impairment after LPS injection. In conclusion, it can be suggested that there is a region-specific response of cell deaths regulators activation in hippocampus and frontal cortex. In addition, elucidating the time profile of events in response to neuroinflammation would be of great help in mechanistic studies and understanding of pathways interaction. J. Cell. Biochem. 118: 4628-4638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Dioscin relieves endotoxemia induced acute neuro-inflammation and protect neurogenesis via improving 5-HT metabolism

PubMed Central

Yang, Rui; Chen, Wei; Lu, Ye; Li, Yingke; Du, Hongli; Gao, Songyan; Dong, Xin; Yuan, Hongbin

2017-01-01

Sepsis, in addition to causing fatality, is an independent risk factor for cognitive impairment among sepsis survivors. The pathologic mechanism of endotoxemia induced acute neuro-inflammation still has not been fully understood. For the first time, we found the disruption of neurotransmitters 5-HT, impaired neurogenesis and activation of astrocytes coupled with concomitant neuro-inflammation were the potential pathogenesis of endotoxemia induced acute neuro-inflammation in sepsis survivors. In addition, dioscin a natural steroidal saponin isolated from Chinese medicinal herbs, enhanced the serotonergic system and produced anti-depressant effect by enhancing 5-HT levels in hippocampus. What is more, this finding was verified by metabolic analyses of hippocampus, indicating 5-HT related metabolic pathway was involved in the pathogenesis of endotoxemia induced acute neuro-inflammation. Moreover, neuro-inflammation and neurogenesis within hippocampus were indexed using quantitative immunofluorescence analysis of GFAP DCX and Ki67, as well as real-time RT-PCR analysis of some gene expression levels in hippocampus. Our in vivo and in vitro studies show dioscin protects hippocampus from endotoxemia induced cascade neuro-inflammation through neurotransmitter 5-HT and HMGB-1/TLR4 signaling pathway, which accounts for the dioscin therapeutic effect in behavioral tests. Therefore, the current findings suggest that dioscin could be a potential approach for the therapy of endotoxemia induced acute neuro-inflammation. PMID:28059131

Peripheral nerve injury alters the expression of NF-κB in the rat's hippocampus.

PubMed

Chou, Chiu-Wen; Wong, Gordon T C; Lim, Grewo; McCabe, Michael F; Wang, Shuxing; Irwin, Michael G; Mao, Jianren

2011-03-10

The hippocampus plays an important role in learning and memory and possibly contributes to the formation of pain-related memory and emotional responses. However, there is currently little data linking the hippocampus to neuropathic pain. It has been reported that NF-κB is an important regulatory factor in memory consolidation within the hippocampus. This study aims to examine a possible relationship between the hippocampal NF-κB expression and nerve injury-induced thermal hyperalgesia using a rat model of constriction sciatic nerve injury (CCI). Immunofluorescence and Western blot analysis were performed to detect and quantify the hippocampal NF-κB expression. Thermal hyperalgesia was examined on day 0 and postoperative days 1, 7 and 14. The nuclear portion of the p65 NF-κB expression was significantly increased on the contralateral side on days 7 and 14 as well as significantly increased on the ipsilateral side on day 14 as compared to the sham control group. Intraperitoneal administration of MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist, reduced hyperalgesia and modulated the NF-κB expression in the contralateral side of hippocampus. These results suggest an association between the hippocampal NF-κB expression and the behavioral manifestation of thermal hyperalgesia, which is likely to be mediated through activation of the NMDA receptor. Copyright © 2011 Elsevier B.V. All rights reserved.

Sleep after Learning Aids Memory Recall

ERIC Educational Resources Information Center

Born, Jan; Gais, Steffen; Lucas, Brian

2006-01-01

In recent years, the effect of sleep on memory consolidation has received considerable attention. In humans, these studies concentrated mainly on procedural types of memory, which are considered to be hippocampus-independent. Here, we show that sleep also has a persisting effect on hippocampus-dependent declarative memory. In two experiments, we…

Temporal Lobe Anatomy and Psychiatric Symptoms in Velocardiofacial Syndrome (22Q11.2 Deletion Syndrome)

ERIC Educational Resources Information Center

Kates, Wendy R.; Miller, Adam M.; Abdulsabur, Nuria; Antshel, Kevin M.; Conchelos, Jena; Fremont, Wanda; Roizen, Nancy

2006-01-01

Objective: To investigate the association between mesial temporal lobe morphology, ratios of prefrontal cortex to amygdala and hippocampus volumes, and psychiatric symptomatology in children and adolescents with velocardiofacial syndrome (VCFS). Method: Scores on behavioral rating scales and volumetric measures of the amygdala, hippocampus, and…

Commentary: Elucidating the Neural Correlates of Early Childhood Memory

ERIC Educational Resources Information Center

Mullally, Sinead L.

2015-01-01

Both episodic memory and the key neural structure believed to support it, namely the hippocampus, are believed to undergo protracted periods of postnatal developmental. Critically however, the hippocampus is comprised of distinct subfields and circuits, and these circuits appear to mature at different rates (Lavenex and Banta Lavenex, 2013).…

Hippocampal Shape Abnormalities of Patients with Childhood-Onset Schizophrenia and Their Unaffected Siblings

ERIC Educational Resources Information Center

Johnson, Sarah L. M.; Wang, Lei; Alpert, Kathryn I.; Greenstein, Deanna; Clasen, Liv; Lalonde, Francois; Miller, Rachel; Rapoport, Judith; Gogtay, Nitin

2013-01-01

Objective: The hippocampus has been implicated in the pathogenesis of schizophrenia, and hippocampal volume deficits have been a consistently reported abnormality, but the subregional specificity of the deficits remains unknown. The authors explored the nature and developmental trajectory of subregional shape abnormalities of the hippocampus in…

The Learning Hippocampus: Education and Experience-Dependent Plasticity

ERIC Educational Resources Information Center

Wenger, Elisabeth; Lövdén, Martin

2016-01-01

The hippocampal formation of the brain plays a crucial role in declarative learning and memory while at the same time being particularly susceptible to environmental influences. Education requires a well-functioning hippocampus, but may also influence the development of this brain structure. Understanding these bidirectional influences may have…

MICROINJECTION OF DYNORPHIN INTO THE HIPPOCAMPUS IMPAIRS SPATIAL LEARNING IN RATS

EPA Science Inventory

The effect of hippocampal dynorphin administration on learning and memory was examined in spatial and nonspatial tasks. ilateral infusion of dynorphin A(1-8)(DYN; 10 or 20 ug in one ul) into the dorsal hippocampus resulted in dose-related impairment of spatial working memory in a...

Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

ERIC Educational Resources Information Center

Drew, Liam J.; Fusi, Stefano; Hen, René

2013-01-01

In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

Images in electroconvulsive therapy: ECS dose-dependently increases cell proliferation in the subgranular region of the rat hippocampus.

PubMed

Smitha, Jangama S M; Roopa, Ravindranath; Sagar, B K Chandrasekhar; Kutty, Bindu M; Andrade, Chittaranjan

2014-09-01

Stress and depression are associated with impaired neuroplasticity in the hippocampus; there is a decrease in neurogenesis, which is hypothesized to decrease the adaptative competence of the organism. Representative light microscopy images are presented which show that 6 once-daily electroconvulsive shocks (ECS), dose-dependently increased new cell formation in the subgranular region of the hippocampus in healthy adult male Wistar rats (10 sections per rat, 3 rats in each of sham ECS, 10 mC, and 40 mC groups). These neuroplasticity changes, demonstrated 1 month after the last ECS, may explain a part of the mechanism of action of electroconvulsive therapy in conditions such as depression.

Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?

PubMed Central

Parent, Marise B.; Baxter, Mark G.

2006-01-01

The neurotransmitter acetylcholine (ACh) has been accorded an important role in supporting learning and memory processes in the hippocampus. Cholinergic activity in the hippocampus is correlated with memory, and restoration of ACh in the hippocampus after disruption of the septohippocampal pathway is sufficient to rescue memory. However, selective ablation of cholinergic septohippocampal projections is largely without effect on hippocampal-dependent learning and memory processes. We consider the evidence underlying each of these statements, and the contradictions they pose for understanding the functional role of hippocampal ACh in memory. We suggest that although hippocampal ACh is involved in memory in the intact brain, it is not necessary for many aspects of hippocampal memory function. PMID:14747512

The complete mitochondrial genome of the big-belly seahorse, Hippocampus abdominalis (Lesson 1827).

PubMed

Wang, Lei; Chen, Zaizhong; Leng, Xiangjun; Gao, Jianzhong; Chen, Xiaowu; Li, Zhongpu; Sun, Peiying; Zhao, Yuming

2016-11-01

In this study, the complete mitogenome sequence of the big-belly seahorse, Hippocampus abdominalis (Lesson, 1827) (Syngnathiformes: Syngnathidae), has been sequenced by the next-generation sequencing method. The assembled mitogenome is 16 521 bp in length which includes 13 protein-coding genes, 22 transfer RNAs, and 2 ribosomal RNAs genes. The overall base composition of the seahorse is 31.1% for A, 23.6% for C, 16.0% for G, 29.3% for T and shows 87% identities similar to tiger tail seahorse, Hippocampus comes. The complete mitogenome of the big-belly seahorse provides essential and important DNA molecular data for further phylogeography and evolutionary analysis for seahorse family.

Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

PubMed

Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

2014-08-01

Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window. Copyright © 2014 Elsevier B.V. All rights reserved.

New records of the Japanese seahorse Hippocampus mohnikei in Southeast Asia lead to updates in range, habitat and threats.

PubMed

Aylesworth, L; Lawson, J M; Laksanawimol, P; Ferber, P; Loh, T-L

2016-04-01

New records of the Japanese seahorse Hippocampus mohnikei from Cambodia, Malaysia, Thailand and Vietnam, along with recently published studies from India and Singapore, have greatly expanded the known range of H. mohnikei within Southeast Asia. These new records reveal novel habitat preferences and threats to H. mohnikei in the region. Although the global conservation status of H. mohnikei is classified as Data Deficient according to the IUCN Red List of Threatened Species, new sightings indicate that this species is found in similar habitats and faces similar threats as other Hippocampus species that are considered Vulnerable. © 2016 The Fisheries Society of the British Isles.

Cholinergic modulation of the hippocampal region and memory function.

PubMed

Haam, Juhee; Yakel, Jerrel L

2017-08-01

Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

3,5,6,7,8,3′,4′-Heptamethoxyflavone, a Citrus Polymethoxylated Flavone, Attenuates Inflammation in the Mouse Hippocampus

PubMed Central

Okuyama, Satoshi; Miyoshi, Kazuhiro; Tsumura, Yuichi; Amakura, Yoshiaki; Yoshimura, Morio; Yoshida, Takashi; Nakajima, Mitsunari; Furukawa, Yoshiko

2015-01-01

Citrus polymethoxylated flavones (PMFs) have recently been shown to suppress inflammation in peripheral tissues. In the present study, we investigated the effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), one of the PMFs, on inflammation in the brain in vivo using mice injected intrahippocampally with lipopolysaccharide (LPS). We demonstrated that subcutaneously injected HMF suppressed: (1) LPS-induced losses in body weight; (2) LPS-induced microglial activation in the hippocampus; and (3) LPS-induced interleukin-1β mRNA expression in the hippocampus. These results suggest that HMF has the ability to reduce neuroinflammation in the brain. PMID:25884208

Intrahippocampal Muscimol Shifts Learning Strategy in Gonadally Intact Young Adult Female Rats

ERIC Educational Resources Information Center

McElroy, Molly W.; Korol, Donna L.

2005-01-01

Learning strategy preferences depend upon circulating estrogen levels, with enhanced hippocampus-sensitive place learning coinciding with elevated estrogen levels. The effects of estrogen on strategy may be mediated by fluctuations in GABAergic function, given that inhibitory tone in the hippocampus is low when estrogen is high. We investigated…

DREAM/Calsenilin/KChIP3 Modulates Strategy Selection and Estradiol-Dependent Learning and Memory

ERIC Educational Resources Information Center

Tunur, Tumay; Stelly, Claire E.; Schrader, Laura Ann

2013-01-01

Downstream regulatory element antagonist modulator (DREAM)/calsenilin(C)/K+ channel interacting protein 3 (KChIP3) is a multifunctional Ca[superscript 2+]-binding protein highly expressed in the hippocampus that inhibits hippocampus-sensitive memory and synaptic plasticity in male mice. Initial studies in our lab suggested opposing effects of…

Rats Depend on Habit Memory for Discrimination Learning and Retention

ERIC Educational Resources Information Center

Broadbent, Nicola J.; Squire, Larry R.; Clark, Robert E.

2007-01-01

We explored the circumstances in which rats engage either declarative memory (and the hippocampus) or habit memory (and the dorsal striatum). Rats with damage to the hippocampus or dorsal striatum were given three different two-choice discrimination tasks (odor, object, and pattern). These tasks differed in the number of trials required for…

Engagement of the PFC in Consolidation and Recall of Recent Spatial Memory

ERIC Educational Resources Information Center

Leon, Wanda C.; Bruno, Martin A.; Allard, Simon; Nader, Karim; Cuello, A. Claudio

2010-01-01

The standard model of system consolidation proposes that memories are initially hippocampus dependent and become hippocampus independent over time. Previous studies have demonstrated the involvement of the medial prefrontal cortex (mPFC) in the retrieval of remote memories. The transformations required to make a memory undergo system's…

a-Band Oscillations in Intracellular Membrane Potentials of Dentate Gyrus Neurons in Awake Rodents

ERIC Educational Resources Information Center

Anderson, Ross W.; Strowbridge, Ben W.

2014-01-01

The hippocampus and dentate gyrus play critical roles in processing declarative memories and spatial information. Dentate granule cells, the first relay in the trisynaptic circuit through the hippocampus, exhibit low spontaneous firing rates even during locomotion. Using intracellular recordings from dentate neurons in awake mice operating a…

Perirhinal and Postrhinal, but Not Lateral Entorhinal, Cortices Are Essential for Acquisition of Trace Eyeblink Conditioning

ERIC Educational Resources Information Center

Suter, Eugenie E.; Weiss, Craig; Disterhoft, John F.

2013-01-01

The acquisition of temporal associative tasks such as trace eyeblink conditioning is hippocampus-dependent, while consolidated performance is not. The parahippocampal region mediates much of the input and output of the hippocampus, and perirhinal (PER) and entorhinal (EC) cortices support persistent spiking, a possible mediator of temporal…

Kindling-Induced Changes in Plasticity of the Rat Amygdala and Hippocampus

ERIC Educational Resources Information Center

Schubert, Manja; Siegmund, Herbert; Pape, Hans-Christian; Albrecht, Doris

2005-01-01

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar…

Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus

EPA Science Inventory

Title (20 words): Effects of developmental exposure to a Commercial PBDE mixture (DE-71) on protein networks in the rat Cerebellum and Hippocampus. Introduction (120 words): Polybrominated diphenyl ethers (PBDE5) possess neurotoxic effects similar to those of PCBs. The cellular a...

Cooperation between the Hippocampus and the Striatum during Episodic Encoding

ERIC Educational Resources Information Center

Sadeh, Talya; Shohamy, Daphna; Levy, Dana Rubi; Reggev, Niv; Maril, Anat

2011-01-01

The hippocampus and the striatum are thought to play distinct roles in learning and memory, each supporting an independent memory system. A fundamental question is whether, and how, these systems interact to jointly contribute to learning and memory. In particular, it remains unknown whether the striatum contributes selectively to implicit,…

Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

ERIC Educational Resources Information Center

Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

2015-01-01

Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

Using Immediate-Early Genes to Map Hippocampal Subregional Functions

ERIC Educational Resources Information Center

Kubik, Stepan; Miyashita, Teiko; Guzowski, John F.

2007-01-01

Different functions have been suggested for the hippocampus and its subdivisions along both transversal and longitudinal axes. Expression of immediate-early genes (IEGs) has been used to map specific functions onto neuronal activity in different areas of the brain including the hippocampus (IEG imaging). Here we review IEG studies on hippocampal…

Dermatitis and systemic mycosis in lined seahorses Hippocampus erectus associated with a marine-adapted Fusarium solani species complex pathogen

USDA-ARS?s Scientific Manuscript database

During a 4 month epizootic, 100% of 152 lined seahorses Hippocampus erectus in three separate groups died while in quarantine following shipment to a public aquarium. Twelve animals with skin depigmentation and ulceration were received by the Aquatic Pathology Service, University of Georgia, College...

Amygdala and Hippocampus Enlargement during Adolescence in Autism

ERIC Educational Resources Information Center

Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

2010-01-01

Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

Theta Coordinated Error Driven Learning in the Hippocampus (Open Access, Publisher’s Version)

DTIC Science & Technology

2013-06-06

assumed to be Hebbian in nature, where individual neurons in an engram join together with synaptic weight increases to support facilitated recall of...together as part of a memory or engram representation, e.g., in the central area CA3 of the hippocampus. With these connections strengthened, the ability

THE ROLE OF THE HIPPOCAMPUS IN OBJECT DISCRIMINATION BASED ON VISUAL FEATURES.

PubMed

Levcik, David; Nekovarova, Tereza; Antosova, Eliska; Stuchlik, Ales; Klement, Daniel

2018-06-07

The role of rodent hippocampus has been intensively studied in different cognitive tasks. However, its role in discrimination of objects remains controversial due to conflicting findings. We tested whether the number and type of features available for the identification of objects might affect the strategy (hippocampal-independent vs. hippocampal-dependent) that rats adopt to solve object discrimination tasks. We trained rats to discriminate 2D visual objects presented on a computer screen. The objects were defined either by their shape only or by multiple-features (a combination of filling pattern and brightness in addition to the shape). Our data showed that objects displayed as simple geometric shapes are not discriminated by trained rats after their hippocampi had been bilaterally inactivated by the GABA A -agonist muscimol. On the other hand, objects containing a specific combination of non-geometric features in addition to the shape are discriminated even without the hippocampus. Our results suggest that the involvement of the hippocampus in visual object discrimination depends on the abundance of object's features. Copyright © 2018. Published by Elsevier Inc.

A place for the hippocampus in the cocaine addiction circuit: Potential roles for adult hippocampal neurogenesis.

PubMed

Castilla-Ortega, Estela; Serrano, Antonia; Blanco, Eduardo; Araos, Pedro; Suárez, Juan; Pavón, Francisco J; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-07-01

Cocaine addiction is a chronic brain disease in which the drug seeking habits and profound cognitive, emotional and motivational alterations emerge from drug-induced neuroadaptations on a vulnerable brain. Therefore, a 'cocaine addiction brain circuit' has been described to explain this disorder. Studies in both cocaine patients and rodents reveal the hippocampus as a main node in the cocaine addiction circuit. The contribution of the hippocampus to cocaine craving and the associated memories is essential to understand the chronic relapsing nature of addiction, which is the main obstacle for the recovery. Interestingly, the hippocampus holds a particular form of plasticity that is rare in the adult brain: the ability to generate new functional neurons. There is an active scientific debate on the contributions of these new neurons to the addicted brain. This review focuses on the potential role(s) of adult hippocampal neurogenesis (AHN) in cocaine addiction. Although the current evidence primarily originates from animal research, these preclinical studies support AHN as a relevant component for the hippocampal effects of cocaine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Levels of retinal IAPP are altered in Alzheimer's disease patients and correlate with vascular changes and hippocampal IAPP levels.

PubMed

Schultz, Nina; Byman, Elin; Wennström, Malin

2018-06-01

Islet amyloid polypeptide (IAPP) forms toxic aggregates in the brain of patients with Alzheimer's disease (AD). Whether IAPP also affects the retina in these patients is still unknown. Levels of IAPP in soluble and insoluble homogenate fractions of retina and hippocampus from AD patients and nondemented controls were analyzed using ELISA. Number of pericytes and vessel length were determined by analysis of immunostained retina and hippocampus. Insoluble retinal fractions of AD patients contained lower levels of unmodified IAPP, whereas soluble retinal fractions contained increased levels of the same. Total IAPP levels and pericyte numbers in retina mirrored corresponding variables in the hippocampus. Moreover, levels of total unmodified IAPP correlated negatively with the vessel length both in retina and hippocampus across the group and positively with pericyte numbers in retina in AD patients. Our studies indicate that changes in brain IAPP are reflected by corresponding levels in the retina. Our results also suggest modification of IAPP as an important event implicated in vascular changes associated with AD. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Effect of hindlimb unloading on stereological parameters of the motor cortex and hippocampus in male rats.

PubMed

Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad

2016-11-09

Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.

Age-Dependent Effects of Acute Alcohol Administration in the Hippocampal Phosphoproteome.

PubMed

Contreras, Ana; Morales, Lidia; Tebourbi, Ali; Miguéns, Miguel; Olmo, Nuria Del; Pérez-García, Carmen

2017-12-18

Alcohol consumption during adolescence is deleterious to the developing brain and leads to persistent deficits in adulthood. Several results provide strong evidence for ethanol-associated alterations in glutamatergic signaling and impaired synaptic plasticity in the hippocampus. Protein phosphorylation is a well-known and well-documented mechanism in memory processes, but information on phosphoprotein alterations in hippocampus after ethanol exposure is limited. This study focuses on age-related changes in the hippocampal phosphoproteome after acute alcohol administration. We have compared the phosphoprotein expression in the hippocampus of adult and adolescent Wistar rats treated with a single dose of ethanol (5 g/kg i.p.), using a proteomic approach including phosphoprotein enrichment by immobilized metal affinity chromatography (IMAC). Our proteomic analysis revealed that 13 proteins were differentially affected by age, ethanol administration, or both. Most of these proteins are involved in neuroprotection and are expressed less in young rats treated with ethanol. We conclude that acute alcohol induces important changes in the expression of phosphoproteins in the hippocampus that could increase the risk of neurodegenerative disorders, especially when the alcohol exposure begins in adolescence.

Temporal Dissociation of Neocortical and Hippocampal Contributions to Mental Time Travel Using Intracranial Recordings in Humans.

PubMed

Schurr, Roey; Nitzan, Mor; Eliahou, Ruth; Spinelli, Laurent; Seeck, Margitta; Blanke, Olaf; Arzy, Shahar

2018-01-01

In mental time travel (MTT) one is "traveling" back-and-forth in time, remembering, and imagining events. Despite intensive research regarding memory processes in the hippocampus, it was only recently shown that the hippocampus plays an essential role in encoding the temporal order of events remembered, and therefore plays an important role in MTT. Does it also encode the temporal relations of these events to the remembering self? We asked patients undergoing pre-surgical evaluation with depth electrodes penetrating the temporal lobes bilaterally toward the hippocampus to project themselves in time to a past, future, or present time-point, and then make judgments regarding various events. Classification analysis of intracranial evoked potentials revealed clear temporal dissociation in the left hemisphere between lateral-temporal electrodes, activated at ~100-300 ms, and hippocampal electrodes, activated at ~400-600 ms. This dissociation may suggest a division of labor in the temporal lobe during self-projection in time, hinting toward the different roles of the lateral-temporal cortex and the hippocampus in MTT and the temporal organization of the related events with respect to the experiencing self.

Hyperthyroidism modifies ecto-nucleotidase activities in synaptosomes from hippocampus and cerebral cortex of rats in different phases of development.

PubMed

Bruno, Alessandra Nejar; Da Silva, Rosane Souza; Bonan, Carla Denise; Battastini, Ana Maria Oliveira; Barreto-chaves, Maria Luiza M; Sarkis, João José Freitas

2003-11-01

Here we investigate the possible effects of the hyperthyroidism on the hydrolysis of the ATP to adenosine in the synaptosomes of hippocampus, cerebral cortex and blood serum of rats in different developmental phases. Manifestations of hyperthyroidism include anxiety, nervousness, tachycardia, physical hyperactivity and weight loss amongst others. The thyroid hormones modulate a number of physiological functions in central nervous system, including development, function, expression of adenosine A(1) receptors and transport of neuromodulator adenosine. Thus, hyperthyroidism was induced in male Wistar rats (5-, 60-, 150- and 330-day old) by daily injections of L-thyroxine (T4) for 14 days. Nucleotide hydrolysis was decreased by about 14-52% in both hippocampus and cerebral cortex in 5 to 60-day-old rats. These changes were also observed in rat blood serum. In addition, in 11-month-old rats, inhibition of ADP and AMP hydrolysis persisted in the hippocampus, whereas, in cerebral cortex, an increase in AMP hydrolysis was detected. Thus, hyperthyroidism affects the extracellular nucleotides balance and adenosine production, interfering in neurotransmitter release, development and others physiological processes in different systems.

Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis.

PubMed

Tumati, Shankar; Martens, Sander; Aleman, André

2013-12-01

Research using proton magnetic resonance spectroscopy (MRS) can potentially elucidate metabolite changes representing early degeneration in Mild Cognitive Impairment (MCI), an early stage of dementia. We integrated the published literature using meta-analysis to identify patterns of metabolite changes in MCI. 29 MRS studies (with a total of 607 MCI patients and 862 healthy controls) were classified according to brain regions. Hedges' g was used as effect size in a random effects model. N-Acetyl Aspartate (NAA) measures were consistently reduced in posterior cingulate (PC), hippocampus, and the paratrigonal white matter (PWM). Creatine (Cr) concentration was reduced in the hippocampus and PWM. Choline (Cho) concentration was reduced in the hippocampus while Cho/Cr ratio was raised in the PC. Myo-inositol (mI) concentration was raised in the PC and mI/Cr ratio was raised in the hippocampus. NAA/mI ratio was reduced in the PC. NAA may be the most reliable marker of brain dysfunction in MCI though mI, Cho, and Cr may also contribute towards this. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.

PubMed

Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin

2016-10-01

Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Interactions between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine.

PubMed

Spignoli, G; Pepeu, G

1987-07-01

The effect of cognition-enhancing agents oxiracetam and aniracetam on scopolamine-induced amnesia and brain acetylcholine decrease was investigated in the rat. Acetylcholine levels were measured by means of a gas-chromatographic method. Scopolamine (0.63 mg/kg IP 60 min before training) prevented the acquisition of a passive avoidance conditioned response ("step through": retest 30 min after training) and brought about a 64, 56 and 42% decrease in acetylcholine level in the cortex, hippocampus and striatum respectively. Oxiracetam (50 and 100 mg/kg IP) administered 30 min before scopolamine reduced the scopolamine-induced amnesic effect and decrease in acetylcholine level in the cortex and hippocampus, but not in the striatum. Lower and higher doses of oxiracetam were ineffective. Aniracetam (100 mg/kg PO) also prevented scopolamine-induced amnesia but attenuated acetylcholine decrease in the hippocampus only. Aniracetam (300 mg PO) reduced acetylcholine decrease in the hippocampus but did not prevent scopolamine-amnesia. In conclusion, oxiracetam and aniracetam exert a stimulatory effect on specific central cholinergic pathways. However, a direct relationship between cognition-enhancing properties and cholinergic activation needs further confirmation.

Effects of fluoride on synapse morphology and myelin damage in mouse hippocampus.

PubMed

Niu, Ruiyan; Chen, Huijuan; Manthari, Ram Kumar; Sun, Zilong; Wang, Jinming; Zhang, Jianhai; Wang, Jundong

2018-03-01

To investigate the fluoride-induced neurotoxicity on mice hippocampus, healthy adult mice were exposed to 25, 50, and 100 mg NaF/L for 60 days. The results showed that medium and high fluoride administration induced ultrastructural alterations in the structure of neuron synapse, including indistinct and short synaptic cleft, and thickened postsynaptic density (PSD). The significant reduced mRNA expressions of proteolipid protein (PLP) in medium and high fluoride groups suggested that myelin damage occurred in hippocampus. The myelin damage in turn was determined by the increased myelin-associated glycoprotein (MAG) level, which is naturally released by injured myelin, in high fluoride group, compared to the medium fluoride group. In addition, high fluoride exposure also reduced the mRNA and protein levels of cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and neural cell adhesion molecule (NCAM). These findings suggested that the alteration in synaptic structure and myelin damage may partly be due to adverse effects of fluoride on the neurotrophy and neuron adhesion in mice hippocampus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neoplasia of captive yellow sea horses (Hippocampus kuda) and weedy sea dragons (Phyllopteryx taeniolatus).

PubMed

LePage, Véronique; Dutton, Christopher J; Kummrow, Maya; McLelland, David J; Young, Karrie; Lumsden, John S

2012-03-01

Syngnathidae is the family of fish that includes sea horses, pipefish, and sea dragons. To date, only a single publication has described neoplasia in syngnathids, a fibrosarcoma of the brood pouch in an aquarium-reared lined sea horse (Hippocampus erectus). From 1998 until 2010, the Toronto Zoo submitted 172 syngnathids for postmortem; species included the spotted or yellow sea horse (Hippocampus kuda), the pot-bellied sea horse (Hippocampus abdominalis) and the weedy sea dragon (Phyllopteryx taeniolatus). Seven neoplasms and two neoplastic-like lesions were identified from these cases. Under light microscopy, the neoplasms had morphological characteristics of a cardiac rhabdomyosarcoma, renal adenocarcinoma, renal adenoma, renal round cell tumors, which were likely lymphomas, exocrine pancreatic carcinoma, and intestinal carcinoma. Of these neoplasms, four had clear evidence of metastasis: the pancreatic and intestinal carcinomas and both round cell tumors. As syngnathids are highly fastidious animals, they can be difficult to maintain in captivity. In order to improve their husbandry, preventative and palliative care, as well as treatment, it is important to investigate and document the types of diseases affecting syngnathids.

White matter structural connectivity and episodic memory in early childhood.

PubMed

Ngo, Chi T; Alm, Kylie H; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S; Olson, Ingrid R

2017-12-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children's performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Theta Oscillations During Active Sleep Synchronize The Developing Rubro-Hippocampal Sensorimotor Network

PubMed Central

Rio-Bermudez, Carlos Del; Kim, Jangjin; Sokoloff, Greta; Blumberg, Mark S.

2017-01-01

Summary Neuronal oscillations comprise a fundamental mechanism by which distant neural structures establish and express functional connectivity. Long-range functional connectivity between the hippocampus and other forebrain structures is enabled by theta oscillations. Here we show for the first time that the infant rat red nucleus (RN)—a brainstem sensorimotor structure— exhibits theta (4-7 Hz) oscillations restricted primarily to periods of active (REM) sleep. At postnatal day (P) 8, theta is expressed as brief bursts immediately following myoclonic twitches; by P12, theta oscillations are expressed continuously across bouts of active sleep. Simultaneous recordings from the hippocampus and RN at P12 show that theta oscillations in both structures are coherent, co-modulated, and mutually interactive during active sleep. Critically, at P12, inactivation of the medial septum eliminates theta in both structures. The developmental emergence of theta-dependent functional coupling between the hippocampus and RN parallels that between the hippocampus and prefrontal cortex. Accordingly, disruptions in the early expression of theta could underlie the cognitive and sensorimotor deficits associated with neurodevelopmental disorders such as autism and schizophrenia. PMID:28479324

Working memory for conjunctions relies on the medial temporal lobe.

PubMed

Olson, Ingrid R; Page, Katie; Moore, Katherine Sledge; Chatterjee, Anjan; Verfaellie, Mieke

2006-04-26

A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays.

Working Memory for Conjunctions Relies on the Medial Temporal Lobe

PubMed Central

Olson, Ingrid R.; Page, Katie; Moore, Katherine Sledge; Chatterjee, Anjan; Verfaellie, Mieke

2006-01-01

A prominent theory of hippocampal function proposes that the hippocampus is importantly involved in relating or binding together separate pieces of information to form an episodic representation. This hypothesis has only been applied to studies of long-term memory because the paradigmatic view of the hippocampus is that it is not critical for short-term forms of memory. However, relational processing is important in many working memory tasks, especially tasks using visual stimuli. Here, we test the hypothesis that the medial temporal lobes are important for relational memory even over short delays. The task required patients with medial temporal lobe amnesia and controls to remember three objects, locations, or object-location conjunctions over 1 or 8 s delays. The results show that working memory for objects and locations was at normal levels, but that memory for conjunctions was severely impaired at 8 s delays. Additional analyses suggest that the hippocampus per se is critical for accurate conjunction working memory. We propose that the hippocampus is critically involved in memory for conjunctions at both short and long delays. PMID:16641239

Estradiol acutely suppresses inhibition in the hippocampus through a sex-specific endocannabinoid and mGluR dependent mechanism

PubMed Central

Huang, Guang Zhe; Woolley, Catherine S.

2012-01-01

SUMMARY The steroid, 17β-estradiol (E2), is well known to influence hippocampal functions such as memory, affective behaviors, and epilepsy. There is growing awareness that in addition to responding to ovarian E2, the hippocampus of both males and females synthesizes E2 as a neurosteroid that could acutely modulate synaptic function. Previous work on acute E2 actions in hippocampus has focused on excitatory synapses. Here, we show that E2 rapidly suppresses inhibitory synaptic transmission in hippocampal CA1. E2 acts through the α form of the estrogen receptor to stimulate postsynaptic mGluR1-dependent mobilization of the endocannabinoid, anandamide, which then retrogradely suppresses GABA release from CB1 receptor-containing inhibitory presynaptic boutons. Remarkably, this effect of E2 is sex-specific, occurring in females but not males. Acute E2 modulation of endocannabinoid tone and consequent suppression of inhibition provides a new mechanism by which neurosteroid E2 could modulate hippocampus-dependent behaviors in a sex-specific manner. PMID:22681685

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

PubMed

Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

2012-10-01

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

A Stereological Study of Synapse Number in the Epileptic Human Hippocampus

PubMed Central

Alonso-Nanclares, Lidia; Kastanauskaite, Asta; Rodriguez, Jose-Rodrigo; Gonzalez-Soriano, Juncal; DeFelipe, Javier

2011-01-01

Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity. PMID:21390290

On the Value of Reptilian Brains to Map the Evolution of the Hippocampal Formation.

PubMed

Reiter, Sam; Liaw, Hua-Peng; Yamawaki, Tracy M; Naumann, Robert K; Laurent, Gilles

2017-01-01

Our ability to navigate through the world depends on the function of the hippocampus. This old cortical structure plays a critical role in spatial navigation in mammals and in a variety of processes, including declarative and episodic memory and social behavior. Intense research has revealed much about hippocampal anatomy, physiology, and computation; yet, even intensely studied phenomena such as the shaping of place cell activity or the function of hippocampal firing patterns during sleep remain incompletely understood. Interestingly, while the hippocampus may be a 'higher order' area linked to a complex cortical hierarchy in mammals, it is an old cortical structure in evolutionary terms. The reptilian cortex, structurally much simpler than the mammalian cortex and hippocampus, therefore presents a good alternative model for exploring hippocampal function. Here, we trace common patterns in the evolution of the hippocampus of reptiles and mammals and ask which parts can be profitably compared to understand functional principles. In addition, we describe a selection of the highly diverse repertoire of reptilian behaviors to illustrate the value of a comparative approach towards understanding hippocampal function. © 2017 S. Karger AG, Basel.

Serotonin receptor 5-HT5A in rat hippocampus decrease by leptin treatment.

PubMed

García-Alcocer, Guadalupe; Rodríguez, Angelina; Moreno-Layseca, Paulina; Berumen, Laura C; Escobar, Jesica; Miledi, Ricardo

2010-12-17

5-Hydroxytryptamine (5-HT) is involved in a variety of different physiological processes and behaviors through the activation of equally diverse receptors subtypes. In this work we studied the changes on the expression of 5-HT(5A) receptors in rat hippocampus induced by leptin, an adipocyte-derived hormone that has been reported to participate in the modulation of food intake and in adult hippocampal neurogenesis. To study the effect of leptin on the 5-HT(5A) receptor gene expression a qRT-PCR was used and the distribution of those receptors in the hippocampus was visualized by immunohistochemistry. Rats were separated in four groups: control (untreated rats), leptin-treated, serotonin-treated and leptin+serotonin treated. The results showed that even though the 5-HT(5A) gene expression did not change in the hippocampus of any of the treated groups, in the rats treated with leptin and serotonin, the specific immunostaining for the 5-HT(5A) serotonin receptor decreased significantly in the dentate gyrus. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Education is associated with sub-regions of the hippocampus and the amygdala vulnerable to neuropathologies of Alzheimer's disease.

PubMed

Tang, Xiaoying; Varma, Vijay R; Miller, Michael I; Carlson, Michelle C

2017-04-01

We evaluated the correlation of educational attainment with structural volume and shape morphometry of the bilateral hippocampi and amygdalae in a sample of 110 non-demented, older adults at elevated sociodemographic risk for cognitive and functional declines. In both men and women, no significant education-volume correlation was detected for either structure. However, when performing shape analysis, we observed regionally specific associations with education after adjusting for age, intracranial volume, and race. By sub-dividing the hippocampus and the amygdala into compatible subregions, we found that education was positively associated with size variations in the CA1 and subiculum subregions of the hippocampus and the basolateral subregion of the amygdala (p < 0.05). In addition, we detected a greater left versus right asymmetric pattern in the shape-education correlation for the hippocampus but not the amygdala. This asymmetric association was largely observed in men versus women. These findings suggest that education in youth may exert direct and indirect influences on brain reserve in regions that are most vulnerable to the neuropathologies of aging, dementia, and specifically, Alzheimer disease.

Education is associated with sub-regions of the hippocampus and the amygdala vulnerable to neuropathologies of Alzheimer’s disease

PubMed Central

Tang, Xiaoying; Varma, Vijay R.; Miller, Michael I.; Carlson, Michelle C.

2018-01-01

We evaluated the correlation of educational attainment with structural volume and shape morphometry of the bilateral hippocampi and amygdalae in a sample of 110 non-demented, older adults at elevated sociodemographic risk for cognitive and functional declines. In both men and women, no significant education-volume correlation was detected for either structure. However, when performing shape analysis, we observed regionally specific associations with education after adjusting for age, intracranial volume, and race. By sub-dividing the hippocampus and the amygdala into compatible subregions, we found that education was positively associated with size variations in the CA1 and subiculum subregions of the hippocampus and the basolateral subregion of the amygdala (p<0.05). In addition, we detected a greater left versus right asymmetric pattern in the shape-education correlation for the hippocampus but not the amygdala. This asymmetric association was largely observed in men versus women. These findings suggest that education in youth may exert direct and indirect influences on brain reserve in regions that are most vulnerable to the neuropathologies of aging, dementia, and specifically, Alzheimer disease. PMID:27535407

White Matter Structural Connectivity and Episodic Memory in Early Childhood

PubMed Central

Ngo, Chi T.; Alm, Kylie H.; Metoki, Athanasia; Hampton, William; Riggins, Tracy; Newcombe, Nora S.; Olson, Ingrid R.

2018-01-01

Episodic memory undergoes dramatic improvement in early childhood; the reason for this is poorly understood. In adults, episodic memory relies on a distributed neural network. Key brain regions that supporting these processes include the hippocampus, portions of the parietal cortex, and portions of prefrontal cortex, each of which shows different developmental profiles. Here we asked whether developmental differences in the axonal pathways connecting these regions may account for the robust gains in episodic memory in young children. Using diffusion weighted imaging, we examined whether white matter connectivity between brain regions implicated in episodic memory differed with age, and were associated with memory performance differences in 4- and 6-year-old children. Results revealed that white matter connecting the hippocampus to the inferior parietal lobule significantly predicted children’s performance on episodic memory tasks. In contrast, variation in the white matter connecting the hippocampus to the medial prefrontal cortex did not relate to memory performance. These findings suggest that structural connectivity between the hippocampus and lateral parietal regions is relevant to the development of episodic memory PMID:29175538

Elevated expression of pleiotrophin in pilocarpine-induced seizures of immature rats and in pentylenetetrazole-induced hippocampal astrocytes in vitro.

PubMed

Zhang, Shuqin; Liang, Feng; Wang, Bing; Le, Yuan; Wang, Hua

2014-03-01

Pleiotrophin (PTN) is a secreted extracellular matrix (ECM)-associated cytokine that has emerged as an important neuromodulator with multiple neuronal functions. In the present study, we detected and compared the dynamic expression of PTN in the hippocampus and adjacent cortex of immature rats with pilocarpine-induced epilepsy. Moreover, we also confirmed the results by examining PTN expression in hippocampal astrocytes cultured in the presence of pentylenetetrazole (PTZ). Immunohistochemistry showed faint immunostaining of PTN in the control hippocampus and adjacent cortex. Notably, PTN immunoreactivity began to increase in relatively small cells in the hippocampus and adjacent cortex at 2h and 3 weeks after seizures, and the labeling intensity reached the maximum level in the hippocampus and adjacent cortex at 8 weeks after seizures. Furthermore, we also found that PTZ treatment significantly reduced astrocytic viability in a dose-dependent manner and time-dependently increased expression levels of PTN in hippocampal astrocytes. In conclusion, our data suggest that increased expression of PTN in the brain tissues may be involved in epileptogenesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Simulating memory outcome before right selective amygdalohippocampectomy.

PubMed

Patrikelis, Panayiotis; Lucci, Giuliana; Siatouni, Anna; Zalonis, Ioannis; Sakas, Damianos E; Gatzonis, Stylianos

2013-01-01

In this paper we present the case of a left-sided speech dominant patient with right medial temporal sclerosis (RMTS) and pharmacoresistant epilepsy who showed improved verbal memory during intracarotid amobarbital test (IAT) at his right hemisphere as compared with his own performance before the drug injection (baseline), as well as after right selective amygdalohippocampectomy. We suggest that the defective verbal memory shown by this patient is due to abnormal activity of his right hippocampus that interfered with the function of his left hippocampus. This hypothesis was demonstrated by the fact that disconnection of the two hippocampi, either by anesthetisation or by resection of the right hippocampus, disengaged the left hippocampus and, consequently improved its function. This paper main objective is twofold: first to contribute to the field of neuropsychology of epilepsy surgery by emphasising on postoperative memory outcomes in right medial temporal lobe epilepsy (RMTLE) patients, particularly those undergoing amygdalohippocampectomy, as the pattern of memory changes after resection of the right temporal lobe is less clear; second, by focusing on memory performance asymmetries during IAT, and comparatively considering them with neuropsychological memory performance, because of their possible prognostic-simulating value.

The Effects of Non-selective Dopamine Receptor Activation by Apomorphine in the Mouse Hippocampus.

PubMed

Arroyo-García, Luis Enrique; Vázquez-Roque, Rubén Antonio; Díaz, Alfonso; Treviño, Samuel; De La Cruz, Fidel; Flores, Gonzalo; Rodríguez-Moreno, Antonio

2018-03-26

Apomorphine is a dopamine receptor agonist that activates D 1 -D 5 dopamine receptors and that is used to treat Parkinson's disease (PD). However, the effect of apomorphine on non-motor activity has been poorly studied, and likewise, the effects of dopaminergic activation in brain areas that do not fulfill motor functions are unclear. The aim of this study was to determine how dopamine receptor activation affects behavior, as well as plasticity, morphology, and oxidative stress in the hippocampus. Adult mice were chronically administered apomorphine (1 mg/kg for 15 days), and the effects on memory and learning, synaptic plasticity, dendritic length, inflammatory responses, and oxidative stress were evaluated. Apomorphine impaired learning and long-term memory in mice, as evaluated in the Morris water maze test. In addition, electrophysiological recording of field excitatory postsynaptic potentials (fEPSP) indicated that the long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus was fully impaired by apomorphine. In addition, a Sholl analysis of Golgi-Cox stained neurons showed that apomorphine reduced the total length of dendrites in the CA1 region of the hippocampus. Finally, there were more reactive astrocytes and oxidative stress biomarkers in mice administered apomorphine, as measured by GFAP immunohistochemistry and markers of redox balance, respectively. Hence, the non-selective activation of dopaminergic receptors in the hippocampus by apomorphine triggers deficiencies in learning and memory, it prevents LTP, reduces dendritic length, and provokes neuronal damage.

Hippocampal volume is decreased in adults with hypothyroidism.

PubMed

Cooke, Gillian E; Mullally, Sinead; Correia, Neuman; O'Mara, Shane M; Gibney, James

2014-03-01

Thyroid hormones are important for the adult brain, particularly regions of the hippocampus including the dentate gyrus and CA1 and CA3 regions. The hippocampus is a thyroid hormone receptor-rich region of the brain involved in learning and memory. Consequently, alterations in thyroid hormone levels have been reported to impair hippocampal-associated learning and memory, synaptic plasticity, and neurogenesis. While these effects have been shown primarily in developing rats, as well as in adult rats, little is known about the effects in adult humans. There are currently no data regarding structural changes in the hippocampus as a result of adult-onset hypothyroidism. We aimed to establish whether hippocampal volume was reduced in patients with untreated adult-onset hypothyroidism compared to age-matched healthy controls. High-resolution magnetization-prepared rapid acquisition with gradient echo (MPRAGE) scans were performed on 11 untreated hypothyroid adults and 9 age-matched control subjects. Hypothyroidism was diagnosed based on increased levels of thyrotropin (TSH) and reduced levels of free thyroxine (fT4). Volumetric analysis of the right and left hippocampal regions, using functional magnetic resonance imaging of the brain (FMRIB) integrated registration and segmentation tool (FIRST), demonstrated significant volume reduction in the right hippocampus in the hypothyroid patients relative to the control group. These findings provide preliminary evidence that hypothyroidism results in structural deficits in the adult human brain. Decreases in volume in the right hippocampus were evident in patients with adult-onset overt hypothyroidism, supporting some of the findings in animal models.

Early effects of 16O radiation on neuronal morphology and cognition in a murine model

NASA Astrophysics Data System (ADS)

Carr, Hannah; Alexander, Tyler C.; Groves, Thomas; Kiffer, Frederico; Wang, Jing; Price, Elvin; Boerma, Marjan; Allen, Antiño R.

2018-05-01

Astronauts exposed to high linear energy transfer radiation may experience cognitive injury. The pathogenesis of this injury is unknown but may involve glutamate receptors or modifications to dendritic structure and/or dendritic spine density and morphology. Glutamate is the major excitatory neurotransmitter in the central nervous system, where it acts on ionotropic and metabotropic glutamate receptors located at the presynaptic terminal and in the postsynaptic membrane at synapses in the hippocampus. Dendritic spines are sites of excitatory synaptic transmission, and changes in spine structure and dendrite morphology are thought to be morphological correlates of altered brain function associated with hippocampal-dependent learning and memory. The aim of the current study is to assess whether behavior, glutamate receptor gene expression, and dendritic structure in the hippocampus are altered in mice after early exposure to 16O radiation in mice. Two weeks post-irradiation, animals were tested for hippocampus-dependent cognitive performance in the Y-maze. During Y-maze testing, mice exposed to 0.1 Gy and 0.25 Gy radiation failed to distinguish the novel arm, spending approximately the same amount of time in all 3 arms during the retention trial. Exposure to 16O significantly reduced the expression of Nr1 and GluR1 in the hippocampus and modulated spine morphology in the dentate gyrus and cornu Ammon 1 within the hippocampus. The present data provide evidence that 16O radiation has early deleterious effects on mature neurons that are associated with hippocampal learning and memory.

Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats.

PubMed

Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole; Sotty, Florence

2017-08-01

Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed a suppression of evoked theta power in ventral hippocampus, while evoked gamma power in mPFC was enhanced in rats administered with PCP neonatally. In addition, increased gamma synchrony elicited by acute administration of the NMDAR antagonist MK-801 was exaggerated in neonatal PCP animals. These data suggest that NMDAR antagonist exposure during brain development alters functional networks within hippocampus and mPFC possibly contributing to the reported behavioral symptoms of this animal model of schizophrenia. NEW & NOTEWORTHY We show that insults with a NMDA receptor antagonist during neurodevelopment lead to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances in the evolvement of schizophrenia-like symptoms and contribute to the understanding of the functional deficits underlying aberrant behavior in this disease. Copyright © 2017 the American Physiological Society.

Temporary conductive hearing loss in early life impairs spatial memory of rats in adulthood.

PubMed

Zhao, Han; Wang, Li; Chen, Liang; Zhang, Jinsheng; Sun, Wei; Salvi, Richard J; Huang, Yi-Na; Wang, Ming; Chen, Lin

2018-05-31

It is known that an interruption of acoustic input in early life will result in abnormal development of the auditory system. Here, we further show that this negative impact actually spans beyond the auditory system to the hippocampus, a system critical for spatial memory. We induced a temporary conductive hearing loss (TCHL) in P14 rats by perforating the eardrum and allowing it to heal. The Morris water maze and Y-maze tests were deployed to evaluate spatial memory of the rats. Electrophysiological recordings and anatomical analysis were made to evaluate functional and structural changes in the hippocampus following TCHL. The rats with the TCHL had nearly normal hearing at P42, but had a decreased performance with the Morris water maze and Y-maze tests compared with the control group. A functional deficit in the hippocampus of the rats with the TCHL was found as revealed by the depressed long-term potentiation and the reduced NMDA receptor-mediated postsynaptic current. A structural deficit in the hippocampus of those animals was also found as revealed the abnormal expression of the NMDA receptors, the decreased number of dendritic spines, the reduced postsynaptic density and the reduced level of neurogenesis. Our study demonstrates that even temporary auditory sensory deprivation in early life of rats results in abnormal development of the hippocampus and consequently impairs spatial memory in adulthood. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Respiratory Viral Infection in Neonatal Piglets Causes Marked Microglia Activation in the Hippocampus and Deficits in Spatial Learning

PubMed Central

Elmore, Monica R. P.; Burton, Michael D.; Conrad, Matthew S.; Rytych, Jennifer L.; Van Alstine, William G.

2014-01-01

Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II+ 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II+. PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important. PMID:24501353

The antidepressant effect of running is associated with increased hippocampal cell proliferation.

PubMed

Bjørnebekk, Astrid; Mathé, Aleksander A; Brené, Stefan

2005-09-01

A common trait of antidepressant drugs, electroconvulsive treatment and physical exercise is that they relieve depression and up-regulate neurotrophic factors as well as cell proliferation and neurogenesis in the hippocampus. In order to identify possible biological underpinnings of depression and the antidepressant effect of running, we analysed cell proliferation, the level of the neurotrophic factor BDNF in hippocampus and dynorphin in striatum/accumbens in 'depressed' Flinders Sensitive Line rats (FSL) and Flinders Resistant Line (FRL) rats with and without access to running-wheels. The FRL strain exhibited a higher daily running activity than the FSL strain. Wheel-running had an antidepressant effect in the 'depressed' FSL rats, as indicated by the forced swim test. In the hippocampus, cell proliferation was lower in the 'depressed' rats compared to the control FRL rats but there was no difference in BDNF or dynorphin levels in striatum/accumbens. After 5 wk of running, cell proliferation increased in FSL but not in FRL rats. BDNF and dynorphin mRNA levels were increased in FRL but not to the same extent in the in FSL rats; thus, increased BDNF and dynorphin levels were correlated to the running activity but not to the antidepressant effect of running. The only parameter that was associated to basal level of 'depression' and to the antidepressant effect was cell proliferation in the hippocampus. Thus, suppression of cell proliferation in the hippocampus could constitute one of the mechanisms that underlie depression, and physical activity might be an efficient antidepressant.

Treadmill running prevents age-related memory deficit and alters neurotrophic factors and oxidative damage in the hippocampus of Wistar rats.

PubMed

Vanzella, Cláudia; Neves, Juliana Dalibor; Vizuete, Adriana Fernanda; Aristimunha, Dirceu; Kolling, Janaína; Longoni, Aline; Gonçalves, Carlos Alberto Saraiva; Wyse, Angela T S; Netto, Carlos Alexandre

2017-09-15

Clinical and pre-clinical studies indicate that exercise is beneficial to many aspects of brain function especially during aging. The present study investigated the effects of a treadmill running protocol in young (3month-old) and aged (22month-old) male Wistar rats, on: I) cognitive function, as assessed by spatial reference memory in the Morris water maze; II) oxidative stress parameters and the expression of neurotrophic factors BDNF, NT-3, IGF-1 and VEGF in the hippocampus. Animals of both ages were assigned to sedentary (non-exercised) and exercised (20min of daily running sessions, 3 times per week for 4weeks) groups. Cognition was assessed by a reference memory task run in the Morris water maze; twenty four hours after last session of behavioral testing hippocampi were collected for biochemical analysis. Results demonstrate that the moderate treadmill running exercise: I) prevented age-related deficits in reference memory in the Morris water maze; II) prevented the age-related increase of reactive oxygen species levels and lipid peroxidation in the hippocampus; III) caused an increase of BDNF, NT-3 and IGF-1 expression in the hippocampus of aged rats. Taken together, results suggest that both exercise molecular effects, namely the reduction of oxidative stress and the increase of neurotrophic factors expression in the hippocampus, might be related to its positive effect on memory performance in aged rats. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of Anterior Nuclei of the Thalamus: A Subcortical Gate in Memory Processing: An Intracerebral Recording Study

PubMed Central

Štillová, Klára; Jurák, Pavel; Chládek, Jan; Chrastina, Jan; Halámek, Josef; Bočková, Martina; Goldemundová, Sabina; Říha, Ivo; Rektor, Ivan

2015-01-01

Objective To study the involvement of the anterior nuclei of the thalamus (ANT) as compared to the involvement of the hippocampus in the processes of encoding and recognition during visual and verbal memory tasks. Methods We studied intracerebral recordings in patients with pharmacoresistent epilepsy who underwent deep brain stimulation (DBS) of the ANT with depth electrodes implanted bilaterally in the ANT and compared the results with epilepsy surgery candidates with depth electrodes implanted bilaterally in the hippocampus. We recorded the event-related potentials (ERPs) elicited by the visual and verbal memory encoding and recognition tasks. Results P300-like potentials were recorded in the hippocampus by visual and verbal memory encoding and recognition tasks and in the ANT by the visual encoding and visual and verbal recognition tasks. No significant ERPs were recorded during the verbal encoding task in the ANT. In the visual and verbal recognition tasks, the P300-like potentials in the ANT preceded the P300-like potentials in the hippocampus. Conclusions The ANT is a structure in the memory pathway that processes memory information before the hippocampus. We suggest that the ANT has a specific role in memory processes, especially memory recognition, and that memory disturbance should be considered in patients with ANT-DBS and in patients with ANT lesions. ANT is well positioned to serve as a subcortical gate for memory processing in cortical structures. PMID:26529407

The role of the hippocampus in recognition memory.

PubMed

Bird, Chris M

2017-08-01

Many theories of declarative memory propose that it is supported by partially separable processes underpinned by different brain structures. The hippocampus plays a critical role in binding together item and contextual information together and processing the relationships between individual items. By contrast, the processing of individual items and their later recognition can be supported by extrahippocampal regions of the medial temporal lobes (MTL), particularly when recognition is based on feelings of familiarity without the retrieval of any associated information. These theories are domain-general in that "items" might be words, faces, objects, scenes, etc. However, there is mixed evidence that item recognition does not require the hippocampus, or that familiarity-based recognition can be supported by extrahippocampal regions. By contrast, there is compelling evidence that in humans, hippocampal damage does not affect recognition memory for unfamiliar faces, whilst recognition memory for several other stimulus classes is impaired. I propose that regions outside of the hippocampus can support recognition of unfamiliar faces because they are perceived as discrete items and have no prior conceptual associations. Conversely, extrahippocampal processes are inadequate for recognition of items which (a) have been previously experienced, (b) are conceptually meaningful, or (c) are perceived as being comprised of individual elements. This account reconciles findings from primate and human studies of recognition memory. Furthermore, it suggests that while the hippocampus is critical for binding and relational processing, these processes are required for item recognition memory in most situations. Copyright © 2017 Elsevier Ltd. All rights reserved.