A grid field calculation model based on perceived speed and perceived angle / 生物医学工程学杂志

The method of directly using speed information and angle information to drive attractors model of grid cells to encode environment has poor anti-interference ability and is not bionic. In response to the problem, this paper proposes a grid field calculation model based on perceived speed and perceived angle. The model has the following characteristics. Firstly, visual stream is decoded to obtain visual speed, and speed cell is modeled and decoded to obtain body speed. Visual speed and body speed are integrated to obtain perceived speed information. Secondly, a one-dimensional circularly connected cell model with excitatory connection is used to simulate the firing mechanism of head direction cells, so that the robot obtains current perception angle information in a biomimetic manner. Finally, the two kinds of perceptual information of speed and angle are combined to realize the driving of grid cell attractors model. The proposed model was experimentally verified. The results showed that this model could realize periodic hexagonal firing field mode of grid cells and precise path integration function. The proposed algorithm may provide a foundation for the research on construction method of robot cognitive map based on hippocampal cognition mechanism.

Neuropathological findings in entorhinal cortex of subjects aged 50 years or older and their correlation with dementia in a sample from Southern Brazil / Achados neuropatológicos no córtex entorrinal de encéfalos de indivíduos acima de 50 anos e sua correlação com demência numa amostra do Sul do Brasil

ABSTRACT. Introduction: The aims of this study were to survey neurodegenerative changes detected by abnormal protein deposits in the Entorhinal Cortex (EC) of subjects aged 50 years or older and to correlate these findings with suspected dementia, as detected by the IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly) . Methods: Fourteen brains were submitted to the immunohistochemistry technique for different proteins (beta-amyloid, tau, -synuclein and phospho-TDP-43) and data obtained compared with IQCODE scores. Results: Fifty-seven percent of the individuals exhibited IQCODE results compatible with dementia, being classified into the demented group (DG): 87.5% of patients had neuropathological findings corresponding to Alzheimer's-like brain pathology (ALBP). Of the patients in the non-demented group (NDG), 16.7% met neuropathological criteria for ALBP. All individuals in the DG showed deposits of more than one kind of protein in the EC. The most common association was hyperphosphorylated tau and beta-amyloid protein (87.5%). Discussion: Most individuals with dementia had neuropathological findings of ALBP, as did one individual with no signs of dementia, characterizing a preclinical stage. The results of this study suggest that deposits of a single type of anomalous protein are normal findings in an aging brain, while more than one kind of protein or the combined presence of anomalous protein deposits indicate the presence of dementia.

RESUMO. Introdução: Este trabalho visa avaliar alterações neurodegenerativas detectadas por depósitos proteicos anormais em Córtex Entorrinal (CE) de indivíduos acima de 50 anos e correlacionar os achados com suspeição de demência detectada por meio do IQCODE (Informant Questionnaire on Cognitive Decline in the Elderly). Métodos: Catorze encéfalos foram submetidos à técnica imuno-histoquímica para diferentes proteínas (beta-amiloide, tau, alfa-sinucleína e fosfo-TDP-43) e esses dados foram comparados com os valores obtidos pelo IQCODE. Resultados: 57% dos indivíduos mostraram resultados de IQCODE compatíveis com demência, sendo classificados no grupo com demência (GD): 87,5% desses pacientes tinham achados neuropatológicos correspondentes a patologia cerebral Alzheimer-símile (ALBP). Entre os pacientes do grupo sem demência (GSD), 16,7% apresentaram critérios neuropatológicos para ALBP. Todos os indivíduos do GD tinham depósitos de mais de um tipo de proteína no CE. A associação proteica mais comum foi tau hiperfosforilada e proteína beta-amiloide (87,5%). Discussão: A maioria dos indivíduos com demência apresentaram achados neuropatológicos de ALBP e um indivíduo, que não tinha evidências de demência, apresentou achados compatíveis com ALBP, caracterizando um estágio pré-clínico. Este trabalho sugere que depósitos de um único tipo de proteína anômala são achados normais do cérebro em envelhecimento, enquanto mais de um tipo de proteínas ou a presença combinada de depósitos proteicos anômalos indica manifestações de demência.

Quantitative evaluation of inhibitory effects of epileptic spikes on theta rhythms in the network of hippocampal CA3 and entorhinal cortex in patients with temporal lobe epilepsy / 生理学报

Epileptic spike is an indicator of hyper-excitability and hyper-synchrony in the neural networks. The inhibitory effects of spikes on theta rhythms (4-8 Hz) might be helpful to understand the mechanism of epileptic damage on the cognitive functions. To quantitatively evaluate the inhibitory effects of spikes on theta rhythms, intracerebral electroencephalogram (EEG) recordings with both sporadic spikes (SSs) and spike-free transient period between adjacent spikes were selected in 4 patients in the status of rapid eyes movement (REM) sleep with temporal lobe epilepsy (TLE) under the pre-surgical monitoring. The electrodes of hippocampal CA3 and entorhinal cortex (EC) were employed, since CA3 and EC built up one of key loops to investigate cognition and epilepsy. These SSs occurred only in CA3, only in EC, or in both CA3 and EC synchronously. Theta power was respectively estimated around SSs and during the spike-free transient period by Gabor wavelet transform and Hilbert transform. The intermittent extent was then estimated to represent for the loss of theta rhythms during the spike-free transient period. The following findings were obtained: (1) The prominent rhythms were in theta frequency band; (2) The spikes could transiently reduce theta power, and the inhibitory effect was severer around SSs in both CA3 and EC synchronously than that around either SSs only in EC or SSs only in CA3; (3) During the spike-free transient period, theta rhythms were interrupted with the intermittent theta rhythms left and theta power level continued dropping, implying the inhibitory effect was sustained. Additionally, the intermittent extent of theta rhythms was converged to the inhibitory extent around SSs; (4) The average theta power level during the spike-free transient period might not be in line with the inhibitory extent of theta rhythms around SSs. It was concluded that the SSs had negative effects on theta rhythms transiently and directly, the inhibitory effects aroused by SSs sustained during the spike-free transient period and were directly related to the intermittent extent. It was indicated that the loss of theta rhythms might qualify exactly the sustained inhibitory effects on theta rhythms aroused by spikes in EEG. The work provided an argumentation about the relationship between the transient negative impact of interictal spike and the loss of theta rhythms during spike-free activity for the first time, offered an intuitive methodology to estimate the inhibitory effect of spikes by EEG, and might be helpful to the analysis of EEG rhythms based on local field potentials (LFPs) in deep brain.

Structural MRI and Amyloid PET Imaging for Prediction of Conversion to Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Meta-Analysis

OBJECTIVE: The aim of this study was to explore the prognostic values of biomarkers of neurodegeneration as measured by magnetic resonance imaging (MRI) and amyloid burden as measured by amyloid positron emission tomography (PET) in predicting conversion to Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS: PubMed and EMBASE databases were searched for structural MRI or amyloid PET imaging studies published between January 2000 and July 2014 that reported conversion to AD in patients with MCI. Means and standard deviations or individual numbers of biomarkers with positive or negative status at baseline and corresponding numbers of patients who had progressed to AD at follow-up were retrieved from each study. The effect size of each biomarker was expressed as Hedges's g. RESULTS: Twenty-four MRI studies and 8 amyloid PET imaging studies were retrieved. 674 of the 1741 participants (39%) developed AD. The effect size for predicting conversion to AD was 0.770 [95% confidence interval (CI) 0.607–0.934] for across MRI and 1.316 (95% CI 0.920–1.412) for amyloid PET imaging (p<0.001). The effect size was 1.256 (95% CI 0.902–1.609) for entorhinal cortex volume from MRI. CONCLUSION: Our study suggests that volumetric MRI measurement may be useful for the early detection of AD.

Modulation of axonal sprouting along rostro-caudal axis of dorsal hippocampus and no neuronal survival in parahippocampal cortices by long-term post-lesion melatonin administration in lithium-pilocarpine model of temporal lobe epilepsy / 대한해부학회지

Feature outcome of hippocampus and extra-hippocampal cortices was evaluated in melatonin treated lithium-pilocarpine epileptic rats during early and chronic phases of temporal lobe epilepsy (TLE). After status epilepticus (SE) induction, 5 and 20 mg/kg melatonin were administered for 14 days or 60 days. All animals were killed 60 days post SE induction and the histological features of the rosrto-caudal axis of the dorsal hippocampus, piriform and entorhinal cortices were evaluated utilizing Nissl, Timm, and synapsin I immunoflorescent staining. Melatonin (20 mg/kg) effect on CA1 and CA3 neurons showed a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus. The number of counted granular cells by melatonin (20 mg/kg) treatment increased along the rostro-caudal axis of the dorsal hippocampus in comparison to the untreated epileptic group. The density of Timm granules in the inner molecular layer of the dentate gyrus decreased significantly in all melatonin treated groups in comparison to the untreated epileptic animals. The increased density of synapsin I immunoreactivity in the outer molecular layer of the dentate gyrus of untreated epileptic rats showed a profound decrease following melatonin treatment. There was no neuronal protection in the piriform and entorhinal cortices whatever the melatonin treatment. Long-term melatonin administration as a co-adjuvant probably could reduce the post-lesion histological consequences of TLE in a region-specific pattern along the rostro-caudal axis of the dorsal hippocampus.

Behavioral effects of deep brain stimulation of the anterior nucleus of thalamus, entorhinal cortex and fornix in a rat model of Alzheimer's disease / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model.</p><p><b>METHODS</b>Forty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed.</p><p><b>RESULTS</b>In the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58).</p><p><b>CONCLUSIONS</b>Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.</p>

The Correlation of Levels of Serum Lipid, Homocysteine, and Folate with Volumes of Hippocampus, Amygdala, Corpus Callosum, and Thickness of Entorhinal Cortex in Patients with Amnestic Mild Cognitive Impairment or Dementia of Alzheimer's Type

OBJECTIVES: In this study, the authors evaluated the correlation between levels of serum lipid, homocysteine, and folate with volumes of hippocampus, amygdala, corpus callosum, and in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) type. METHODS: The study recruited patients who visited the dementia clinic of Haeundae Paik Hospital in Korea between March 2010 and June 2014. Among those, patients who had taken the neurocognitive test, brain magnetic resonance imaing, tests for serum lipid, homocysteine, folate, and apolipoprotein E (APOE) genotyping and diagnosed with aMCI or AD were included for analysis. Bilateral hippocampus, entorhinal cortex, amygdala and corpus callosum were selected for region of interest (ROI). The cross-sectional relationships between serum lipid, homocysteine, folate and ROI were assessed by partial correlation analysis and multiple linear regression analysis. RESULTS: In patients with aMCI, old age (> 80) and APOE epsilon4 carrier were associated with AD [odds ration (OR) : 12.80 ; 95% confidence interval (CI) : 2.25-72.98 and OR : 4.48 ; 95% CI : 1.58-12.67, respectively]. In patients with aMCI or AD, volumes and thickness of ROI were inversely correlated with levels of serum lipid and homocysteine. In multiple linear regression analyses, higher total cholesterol level was related to lower left, right hippocampus volume and left amygdala volume ; higher low-density lipoprotein cholesterol was related to lower right entorhinal cortex thickness ; higher homocysteine level was related to lower corpus callosum volume. CONCLUSIONS: Higher serum lipid and homocysteine levels are associated with decreased volume of hippocampus, amygdala, corpus callosum and entorhinal cortex thickness in patients with aMCI or AD. These findings suggest that serum lipid and homocysteine levels are associated with AD as a modifiable risk factor.

Volume changes of cortical and subcortical reward circuitry in the brain of patients with type 2 diabetes mellitus / 南方医科大学学报

<p><b>OBJECTIVE</b>To elucidate the volume changes of cortical and subcortical reward circuitry in patients with type 2 diabetes mellitus.</p><p><b>METHODS</b>High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images were obtained from 16 patients with type 2 diabetes mellitus and 16 normal controls, and 11 type 2 diabetic patients also received the same MRI scans after insulin therapy for 1 year. Volumetric analysis was performed and analysis of covariance and paired t test were applied.</p><p><b>RESULTS</b>A decreased volume was found in the left insular lobe, left nucleus accumbens area, right hippocampus, putamen and amygdala in type 2 diabetic patients compared with normal controls (P<0.05). After insulin therapy for 1 year, an increased volume of bilateral cortical reward structures was observed (left, 33.65∓3.66 ml; right, 33.35∓4.25 ml) compared the baseline level (left, 31.45∓2.90 ml; right, 31.12∓2.97 ml) in diabetic patients (P<0.05). No significant volume change in the bilateral basal ganglia structures was found after insulin therapy for 1 year (P>0.05), and bilateral ventral diencephalon area showed an increased volume after the treatment (left, 3.26∓0.68 ml; right, 3.20∓0.78 ml) compared with the baseline (left, 2.96∓0.76 ml; right, 2.82∓0.90 ml)(P<0.05).</p><p><b>CONCLUSION</b>Type 2 diabetic patients have a decreased volume of the cortical and subcortical reward circuitry, and insulin therapy can reverse such changes and improve the damage of reward circuitry.</p>

Facilitation of synaptic transmission and connections of entorhinal-hippocampal pathway by 5-HT2C receptor subtype: multi-electrode array recordings / 生理学报

Using 64-channels (8 × 8) multi-electrode array technique (MED-64 system), the modulatory actions of 5-hydroxytryptamine (5-HT) 2C receptor subtype on the entorhinal (EC)-hippocampal synaptic transmission and connections were studied. One of freshly dissociated acute hippocampal slices of rats which was placed on the MED-64 probe, was subject to constant perfusion with oxygenated artificial cerebrospinal fluid (ACSF, 95% O2 and 5% CO2). Two hours after ACSF incubation, simultaneous multi-site electrophysiological recordings were performed. One electrode was selected to be used for perforant path (PP) stimulation, and the remaining 63 electrodes were used for recordings of network field excitatory postsynaptic potentials (fEPSPs) within both CA1 and dentate gyrus (DG) that have been previously proved to be mediated by glutamate non-NMDA receptors. After stability of network fEPSPs was achieved, (±)-1(2, 5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI, an agonist of 5-HT2C receptor subtype), or SB242084 (6-Chloro-2,3-dihydro-5-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]-1H-indole-1-carboxyamide dihydrochloride hydrate) (a selective antagonist of 5-HT2C receptor subtype) was applied for 10 min perfusion, respectively. Two-dimensional current source density (2D-CSD) analysis was also transformed by bilinear interpolation at each point of the 64 electrodes for spatial imaging of the fEPSP network responses. Based upon the polarities of fEPSP and 2D-CSD imaging, it was clearly shown that synaptic activations were evoked to occur within the molecular layer of DG and pyramidal cell layer of CA1 by the PP stimulation in which negative-going field potentials and current sink (blue) could be recorded. While, positive-going field potentials and current source (yellow) were mainly localized within the granule cell layer and hilus of DG and alveus of CA1, reflecting spread of electrical signals derived from depolarized region toward CA3 area or subiculum and fimbria along the axons. Perfusion of the hippocampal slices with DOI resulted in a significant enlargement of synaptic connection size at network level and enhancement of synaptic efficacy. However, on the contrary, perfusion with SB242084 produced reversal effect with either reduction in synaptic network size or decreased magnitude of fEPSPs (amplitude and slope) in the CA1 and DG. These results suggest that endogenous 5-HT causes facilitation of EC-CA1 and EC-DG synaptic transmission and connections via acting on 5-HT2C receptor subtype, leading to gain in synaptic transmission and enlargement of synaptic connections.

Effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and spatial learning in rats

The dorsal striatum plays an important role in the control of motor activity and learning processes within the basal ganglia circuitry. Furthermore, recent works have suggested functional differentiation between subregions of the dorsal striatum. The present study examined the effects of bilateral electrolytic lesions of the dorsomedial striatum on motor behavior and learning ability in rats using a series of behavioral tests. 20 male wistar rats were used in the experiment and behavioral assessment were conducted using open field test, rotarod test and 8-arm radial maze. In the open field test, rats with bilateral electrolytic lesions of the dorsomedial striatum showed a normal motor function in the horizontal locomotor activity, while in rearing activity they displayed a statistically significant motor impairment when compared to sham operated group. In the rotarod test, a deficit in motor coordination and acquisition of skilled behavior was observed in rats with bilateral electrolytic lesions of the dorsomedial striatum compared to sham. However, radial maze performance revealed similar capacity in the acquisition of learning task between experimental groups. Our results support the premise of the existence of functional dissociation between the dorsomedial and the dorsolateral regions of the dorsal striatum. In addition, our data suggest that the associative dorsomedial striatum may be as critical in striatum-based motor control

Determination of the rCBF in the Amygdala and Rhinal Cortex Using a FAIR-TrueFISP Sequence

OBJECTIVE: Brain perfusion can be assessed non-invasively by modern arterial spin labeling MRI. The FAIR (flow-sensitive alternating inversion recovery)-TrueFISP (true fast imaging in steady precession) technique was applied for regional assessment of cerebral blood flow in brain areas close to the skull base, since this approach provides low sensitivity to magnetic susceptibility effects. The investigation of the rhinal cortex and the amygdala is a potentially important feature for the diagnosis and research on dementia in its early stages. MATERIALS AND METHODS: Twenty-three subjects with no structural or psychological impairment were investigated. FAIR-True-FISP quantitative perfusion data were evaluated in the amygdala on both sides and in the pons. A preparation of the radiofrequency FOCI (frequency offset corrected inversion) pulse was used for slice selective inversion. After a time delay of 1.2 sec, data acquisition began. Imaging slice thickness was 5 mm and inversion slab thickness for slice selective inversion was 12.5 mm. Image matrix size for perfusion images was 64 x 64 with a field of view of 256 x 256 mm, resulting in a spatial resolution of 4 x 4 x 5 mm. Repetition time was 4.8 ms; echo time was 2.4 ms. Acquisition time for the 50 sets of FAIR images was 6:56 min. Data were compared with perfusion data from the literature. RESULTS: Perfusion values in the right amygdala, left amygdala and pons were 65.2 (+/- 18.2) mL/100 g/minute, 64.6 (+/- 21.0) mL/100 g/minute, and 74.4 (+/- 19.3) mL/100 g/minute, respectively. These values were higher than formerly published data using continuous arterial spin labeling but similar to 15O-PET (oxygen-15 positron emission tomography) data. CONCLUSION: The FAIR-TrueFISP approach is feasible for the quantitative assessment of perfusion in the amygdala. Data are comparable with formerly published data from the literature. The applied technique provided excellent image quality, even for brain regions located at the skull base in the vicinity of marked susceptibility steps.

Effect of yizhi jiannao granule concentration fluid on the differential expression protein in entorhinal area tissue of senescence accelerated mouse P8 / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the mechanism of Yizhi Jiannao Granule (YZJN) in treating Alzheimer's disease (AD) on proteomic level by analyzing the differential expression proteins in entorhinal cortex tissue of senescence accelerated mouse P8 (SAMP8) treated with YZJN.</p><p><b>METHODS</b>Six-month old SAMP8 were randomly divided into 3 groups, the model group, the YZJN group and the control group, 10 mice in each group. The model group was untreated with free water access, the YZJN group was treated with concentrated water extract of YZJN 0.3 g per day via gastric perfusion, and the control group was perfused with equal volume of double distilled water. The total protein in entorhinal cortex tissue of mice was extracted after an 8-week treatment with two-dimensional gel electrophoresis, and the differential expression protein spots were separated for identification through peptide mass fingerprint analysis and database searching.</p><p><b>RESULTS</b>Thirty-two protein spots expressed differentially between the YZJN group and the model group were found, and 14 differential expression proteins were identified, including NADH dehydrogenase iron-sulfur protein 6, Rho-GDP dissociation inhibitor alpha, beta2-globin, phosphoglyceric kinase, etc, their functions involved mitochondria energy metabolism, oxidative stress and neuron function.</p><p><b>CONCLUSION</b>YZJN could regulate multiple protein expressions in entorhinal cortex tissues of SAMP8, suggesting that it has multi-target therapeutic action and its mechanism in treating AD is possibly realized by way of improving mitochondria function, antagonizing oxidation stress, preventing nerve cell apoptosis and protecting neurons.</p>

Gene Knockdown in the Olfactory Bulb, Amygdala, and Hypothalamus by Intranasal siRNA Administration / 대한해부학회지

Intranasal administration provides a method of bypassing the blood brain barrier, which separates the systemic circulating system and central interstitial fluid, and directly delivering drugs to the central nervous system. This method also circumvents first-pass elimination by the liver and gastrointestinal tract. In the present study, the authors investigated intranasal siRNA delivery efficiency by using FITC-labeled transfection control siRNA and a genespecific siRNA. The localization of fluorescence-tagged siRNA revealed that siRNA was delivered to cells in the olfactory bulb and that the level of the siRNA target gene (alpha B-crystallin) was significantly reduced in the same area. siRNA was delivered to processes as well as nuclei and cytoplasm. At 12 hrs after intranasal delivery, siRNA-mediated target gene reduction was observed in other more distally located brain regions, for example, in the amygdala, entorhinal cortex, and hypothalamus. Target gene knockdown was demonstrated by double immunohistochemistry, which demonstrated alpha B crystallin expression depletion in more than 70% of cells at 12 hrs after the intranasal delivery. siRNA-mediated target gene suppression was detected not only in neurons but in glia, for example, astrocytes. These results indicate that intranasal siRNA delivery offers an efficient means of reducing specific target genes in certain regions of the brain and of performing gene knockdown-mediated therapy.

Empathy and Mood Awareness Reflected in the Resting-State Brain Metabolic Activity in the Patients with Schizophrenia and Normal Subjects

OBJECTIVES: Empathy has been conceptualized as the ability of emotional resonance and perspective-taking. Emotional awareness has been proposed as the basis of empathy. In this study we examined the relationship between empathy and mood awareness and their neural correlates in resting-state activity in normal controls and patients with schizophrenia. METHODS: Empathy and mood awareness scale scores were compared between 29 patients with schizophrenia and 21 normal controls by voxel-based t-tests and voxel-based correlation analyses of resting-state 18F-FDG PET images. RESULTS: Empathy and mood labeling scale scores were significantly decreased in schizophrenic patients. Mood monitoring was positively correlated with empathy score in normal controls, but not in schizophrenic patients. In normal controls, empathy was positively correlated with resting-state activities in the intraparietal sulcus and mood monitoring was positively correlated with the temporal pole, frontopolar cortex, inferior temporal gyrus, entorhinal cortex and the subgenual prefrontal cortex resting activities. The orbitofrontal cortex resting activity was positively correlated with mood monitoring-related subgenual prefrontal cortex activity in the normal controls. Patients with schizophrenia showed decreased orbitofrontal resting activity and loss of its correlations with mood monitoring-related regional activities. CONCLUSION: This study showed that alteration in the resting-state activity in schizophrenia may reflect dysfunctional empathy and distorted characteristic of emotional awareness. However, the resting-state activity may not reflect the relationship between emotional awareness and empathy.

Differential role of entorhinal and hippocampal nerve growth factor in short- and long-term memory modulation

We studied the effects of infusion of nerve growth factor (NGF) into the hippocampus and entorhinal cortex of male Wistar rats (250-300 g, N = 11-13 per group) on inhibitory avoidance retention. In order to evaluate the modulation of entorhinal and hippocampal NGF in short- and long-term memory, animals were implanted with cannulae in the CA1 area of the dorsal hippocampus or entorhinal cortex and trained in one-trial step-down inhibitory avoidance (foot shock, 0.4 mA). Retention tests were carried out 1.5 h or 24 h after training to measure short- and long-term memory, respectively. Immediately after training, rats received 5 æl NGF (0.05, 0.5 or 5.0 ng) or saline per side into the CA1 area and entorhinal cortex. The correct position of the cannulae was confirmed by histological analysis. The highest dose of NGF (5.0 ng) into the hippocampus blocked short-term memory (P < 0.05), whereas the doses of 0.5 (P < 0.05) and 5.0 ng (P < 0.01) NGF enhanced long-term memory. NGF administration into the entorhinal cortex improved long-term memory at the dose of 5.0 ng (P < 0.05) and did not alter short-term memory. Taken as a whole, our results suggest a differential modulation by entorhinal and hippocampal NGF of short- and long-term memory.

Immunochemical and morphometric features of astrocyte reactivity vs. plaque location in Alzheimer's disease

The quantitative relationship between glial fibrillary acidic protein (GFAP) hyper-reactivity and -amyloid protein (AP) deposition was investigated by double immunoperoxidase labeling of hippocampal and entorhinal cortex sections from five Alzheimer´s disease (AD) cases and five age-matched controls. AP plaques, which were absent in controls, were found in all AD samples, without significant differences in number or perimeter according to their location among the regions studied. In contrast, the mean number of GFAP (+) cells was significantly greater in the hippocampus than in the entorhinal cortex from AD cases (49 vs.39). Although at lower values (30 vs. 20), predominance of astrocyte hyperplasia in hippocampus as compared with entorhinal cortex was also found in control samples. Concomitant astrocyte hypertrophy, as defined by surface density (Sv) values of GFAP-immunoreactive material exceeding those of control means, affected a similar proportion of cells in the hippocampus (73%) and the entorhinal cortex (74%) from AD cases. Since an increased number of GFAP (+) cells in the hippocampus was not accompanied by an increased number and/or perimeter of neighbouring plaques, such differential hyper-reactivity in samples from AD patients, as well as in those with normal aging, seems to depend partially on the regional location of the involved astrocyte.

Changes of the Cholinergic Innervation to the Hippocampus after Entorhinal Cortex Lesion in Rat / 대한해부학회지

The hippocampus is known as involved in learning and memory functions and the entorhinal cortex plays a crucial role as a gateway connecting the several areas and hippocampal formation. Entorhinal cortex lesions have been employed in numerous studies as the Alzheimer's disease model. The purpose of this study were to identify the CNS hip-pocampal and cholinergic pathway and to investigate the morphological changes of the hippocampal cholinergic inner-vations by using the Pseudorabies virus injection into the hippocampus after entorhinal cortex lesions. The pseudorabies virus and double labelled neurons (ChAT and PRV) were distributed at several different nuclei including agranular insular cortex, bed nucleus of stria terminalis, central amygdala, globus pallidus, lateral segment, lateral hypothalamic area, laterodorsal tegmental nucleus, medial septal nucleus, mesencephalic reticular nucleus, periaqueductal gray matter and substantia innominata The morphological changes were observed in the hippocampal cholinergic innervation after entorhinal cortex lesions. These data suggested that the hippocampal cholinergic innervation showed morphological changes throughout the whole brain areas after entorhinal cortex lesion.

Nip2 Expression of Postnatal, Aged and Transient Focal Cerebral Ischemic Rat / 대한해부학회지

Nip2 mRNA expression of hippocampus was clarified in the postnatal, adult and aging rat. We observed the change of Nip2 mRNA expression in the ischemic rat hippocampus at 3, 6, 24 and 72 hours after reperfusion. And we investigated the relation between Nip2 and apoptosis after ischemic insults. The Rats were killed 2, 4, 7 days after birth and normal adult rats and aged rat were killed. Male F344 rats were subjected to transient middle cerebral artery occlusion. Reperfusion was achieved by withdrawing the filament after 90 min minutes, and rats were sacrificed 3, 6, 24, 72 hours after reperfusion. Hippocampal sections were stained for TUNEL using ApopTag kit following the protocol provided by the manufacturer, and stained with 2, 3, 5 -triphenyl tetrazolium chloride and cresyl violet We used quantitative reverse transcription and polymerase chain reaction to characterise changes in the mRNA expression of Nip2 in the rat models of transient focal ischemia and postnatal, adult and aged rat. Nip2 mRNA expression were increased in the rat of postnatal development and aging more than these of adult. After reperfusion, marked increase of Nip2 mRNA was observed after 3 and 6 hours. After that time mRNA expression of Nip2 was decreased gradually. The TUNEL staining detected DNA fragmentation in neurons of the entorhinal cortex, forcep major corpus callosum and secondary visual cortex at 24 hours. And TTC staining results showed the whitish infact changes of hippocampal CA1 region and lateral habenular nucleus. We hypothesize that the overexpression of Nip2 is concerned with sensitivity to the ischemic insult at postnatal period and aging period. And, early apoptotic events after cerebral ischemic insults relate to Nip2 mRNA overexpression.

Retrograde Amnesia Following Anterior Thalamic Infarction

BACKGROUND: Retrograde amnesia (RA) refers to the failure to recall events that occurred before a brain injury. RA is known to be associated with brain lesions involving the hippocampus, entorhinal cortex and the frontal lobe. Anterior thalamic lesion often causes anterograde amnesia but rarely causes RA. The aim of the present study is in two parts . First, we discuss the neuroanatomical perspectives of RA based on our case with severe RA after a right anterior thalamic infarction. Second, we introduce a test for RA termed the "Korean Public Events Recall Test (K-PERT)", which was developed based on famous Korean public events from 1966 to 1997. METHODS: A 62-year-old woman with transient RA after a left anterior thalamic infarction 4 years ago presented severe and persistent RA following a right anterior thalamic infarction. We followed up the patient with neuropsychological tests. We also performed the K-PERT on the patient as well as on 14 women of the same age and education. RESULTS: Neuropsychological tests showed severe impairment in autobiographical memory with frontal lobe dysfunction. On K-PERT, the normal controls scored 13.7 +/- 3.7 in recall and 21.2 +/- 3.1 in recognition out of a maximum score of 30, whereas the patient obtained only 3/30 and 4/30, respectively. CONCLUSIONS: In our case, RA might have resulted from damage to the pathway that retrieves old memories, which are stored in the frontal lobe. Thus, anterior thalamus might be viewed as the gate of memory engram. Further studies are needed to elaborate the usefulness of K-PERT as an objective tool for investigating remote memory.

Calcium Influx is Responsible for Afterdepolarizations in Rat Hippocampal Dentate Granule Cells

Granule cells in dentate gyrus of hippocampus relay information from entorhinal cortex via perforant fiber to pyramidal cells in CA3 region. Their electrical activities are known to be closely associated with seizure activity as well as memory acquisition. Since action potential is a stereotypic phenomena which is based on all-or-none principle of Na+ current, the neuronal firing pattern is mostly dependent on afterpotentials which follows the stereotypic Na+ spike. Granule cells in dentate gyrus show afterdepolarization (ADP), while interneurons in dentate gyrus have afterhyperpolarizaton. In the present study, we investigated the ionic mechanism of afterdepolarization in hippocampal dentate granule cell. Action potential of dentate granule cells showed afterdepolarization, which was characterized by a sharp notch followed by a depolarizing hump starting at about -49.04 +/- 1.69 mV (n=43, mean +/- SD) and lasting 3~7 ms. Increase of extracellular Ca2+ from 2 mM to 10 mM significantly enhanced the ADP both in amplitude and in duration. A K+ channel blocker, 4-aminopyridine (4-AP, 2 mM), enhanced the ADP and often induced burst firings. These effects of 10 mM Ca2+ and 4-AP were additive. On the contrary, the ADP was significantly suppressed by removal of external Ca2+, even in the presence of 4-AP (2 mM). A Na+ channel blocker, TTX (100 nM), did not affect the ADP. From these results, it is concluded that the extracellular Ca2+ influx contributes to the generation of ADP in granule cells.