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RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating G_i/o-mediated inhibition of presynaptic Ca²⁺ channels

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NEURON 2006年第5期51卷 575-586页

作者： Han, Jing Mark, Melanie D. Li, Xiang Xie, Mian Waka, Sayumi Rettig, Jens Herlitze, Stefan Case Western Reserve Univ Sch Med Dept Neurosci Cleveland OH 44106 USA Univ Saarland Dept Physiol D-66421 Homburg Germany

RGS2, one of the small members of the regulator of G protein signaling (RGS) family, is highly expressed in brain and regulates G(i/o) as well as G(q)-coupled receptor pathways. RGS2 modulates anxiety, aggression, and blood pressure in mice, suggesting that RGS2 regulates synaptic circuits underlying animal physiology and behavior. How RGS2 in brain influences synaptic activity is unknown. We therefore analyzed the synaptic function of RGS2 in hippocampal neurons by comparing electrophysiological recordings from RGS2 knockout and wild-type mice. Our study provides a general mechanism of the action of the RGS family containing RGS2 by demonstrating that RGS2 increases synaptic vesicle release by downregulating the G(i/o)-mediated presynaptic Ca2+ channel inhibition and therefore provides an explanation of how regulation of RGS2 expression can modulate the function of neuronal circuits underlying behavior.

关键词： Animals Blotting, Western Blotting, Western Calcium Channels/metabolism Cells, Cultured Hippocampus/metabolism Humans image processing, computer-assisted Immunohistochemistry Immunohistochemistry In Situ Hybridization In Situ Hybridization Mice Mice, Knockout Mice, Knockout Neuronal Plasticity/physiology Neurons/metabolism Reverse Transcriptase Polymerase Chain Reaction RGS Proteins/metabolism Synapses/metabolism Synaptic Transmission/physiology Synaptic Vesicles/metabolism

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White matter growth as a mechanism of cognitive development in children

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NEUROimage 2006年第3期33卷 936-946页

作者： Mabbott, Donald J. Noseworthy, Michael Bouffet, Eric Laughlin, Suzanne Rockel, Conrad Hosp Sick Children Res Inst Brain & Behav Program Toronto ON M5G 1X8 Canada Univ Toronto Dept Paediat Toronto ON Canada St Josephs Healthcare Brain Body Inst Hamilton ON Canada McMaster Univ Dept Radiol Hamilton ON Canada McMaster Univ Dept Med Phys Hamilton ON Canada Hosp Sick Children Div Haematol Oncol Toronto ON M5G 1X8 Canada Univ Toronto Dept Med Imaging Toronto ON Canada Hosp Sick Children Toronto ON M5G 1X8 Canada

We examined the functional role of white matter growth in cognitive development. Specifically, we used hierarchical regression analyses to test the unique contributions of age versus white matter integrity in accounting for the development of information processing speed. Diffusion tensor imaging was acquired for 17 children. and adolescents (age range 6-17 years), with apparent diffusion coefficient (ADC) and fractional anisotropy (FA) calculated for 10 anatomically defined fiber pathways and 12 regions of hemispheric white matter. Measures of speeded visual-spatial searching, rapid picture naming, reaction time in a sustained attention task, and intelligence were administered. Age- related increases were evident across tasks, as well as for white matter integrity in hemispheric white matter. ADC was related to few measures. FA within multiple hemispheric compartments predicted rapid picture naming and standard error of reaction time in sustained attention, though it did not contribute significantly to the models after controlling for age. Independent of intelligence, visual-spatial searching was related to FA in a number of hemispheric regions. A novel finding was that only right frontal-parietal regions contributed uniquely beyond the effect of age in accounting for performance: age did not contribute to visual-spatial searching when FA within these regions was first included in the models. Considering we found that both FA in right frontal- parietal regions and speed of visual-spatial searching increased with age, our findings are consistent with the growth of regional white matter organization as playing an important role in increased speed of visual searching with age. (c) 2006 Elsevier Inc. All rights reserved.

关键词： Adolescent Aging/physiology Anisotropy Attention/physiology Brain/anatomy & histology Brain/growth & development Child Child Development/physiology Cognition/physiology Diffusion Magnetic Resonance Imaging Female Humans image processing, computer-assisted Male Neural Pathways/anatomy & histology Neural Pathways/physiology Psychomotor Performance/physiology Reaction Time/physiology Regression Analysis Space Perception/physiology Visual Perception/physiology

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Between session reproducibility and between subject variability of diffusion MR and tractography measures

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NEUROimage 2006年第3期33卷 867-877页

作者： Heiervang, E. Behrens, T. E. J. Mackay, C. E. Robson, M. D. Johansen-Berg, H. Univ Oxford John Radcliffe Hosp Ctr Funct Magnet Resonance Imaging Brain Oxford OX3 9DU England Haukeland Hosp Dept Child & Adolescent Mental Hlth N-5021 Bergen Norway Univ Oxford John Radcliffe Hosp Clin Magnet Resonance Res Oxford OX3 9DU England

As diffusion tractography is increasingly used to generate quantitative measures to address clinical questions, it is important to characterise the inter-session reproducibility and inter-subject variability of these measures. Here, we assess the reproducibility and variability of diffusion tractography measures using diffusion data from 8 subjects scanned 3 times. We used probabilistic tractography to define the cingulum bundle, pyramidal tracts, optic radiations and germ of the corpus callosum in each individual data set using three different methods of seed definition. Measures of mean fractional anisotropy (FA) and mean diffusivity (MD) along the tracts were more reproducible than measures of tract volume. Further, tracts defined using a two region of interest (ROI) approach were more reproducible than those defined using manually placed seed masks alone. For mean FA taken from tracts defined using the two ROI approach, inter-session coefficients of variation (CV) were all below 5% and inter-subject CVs were below 10%;for mean MD inter-session, CVs were all below 3% and inter-subject CVs were below 8%. We use the variability measures found here to calculate the sample sizes required to detect changes in FA, MD or tract volume of a given size, either between groups of subjects or within subjects over time. Finally, we compare tractography results using 60 diffusion encoding directions to those found using a subset of 12 directions;the number of diffusion directions did not have a significant effect on reproducibility, but tracts derived using fewer directions were consistently smaller than those derived using 60 direction data. We suggest that 12 direction data are sufficient for reproducibly defining the core of large bundles but may be less sensitive to smaller pathways. (c) 2006 Elsevier Inc. All rights reserved.

关键词： Adult Brain/anatomy & histology Brain/pathology Diffusion Magnetic Resonance Imaging/statistics & numerical data Female Humans image processing, computer-assisted Male Mesencephalon/anatomy & histology Pyramidal Tracts/anatomy & histology Reproducibility of Results Sample Size

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Fully-automated detection of cerebral water content changes:: Study of age- and gender-related H₂O patterns with quantitative MRI

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NEUROimage 2006年第3期29卷 910-922页

作者： Neeb, H Zilles, K Shah, NJ Forschungszentrum Julich Inst Med D-52425 Julich Germany Brain Imaging Ctr W D-52425 Julich Germany Univ Dortmund Inst Phys D-44221 Dortmund Germany

We present a simple and robust method for the automated image analysis of quantitative cerebral water content maps acquired with MRI. The method is based on a new approach for the absolute and quantitative mapping of water content in vivo. Water content maps were automatically segmented into grey and white matter by employing the quantitative T, information acquired as part of the water content mapping procedure. Based on the segmented maps, twenty-two parameters sensitive to both absolute water content and its spatial organisation are automatically extracted without user interaction. The parameters include, amongst others, absolute water content in grey and white matter and spatial asymmetries of the cerebral water content distribution. Significant age- and gender-related changes in the parameters determined were observed in a study of forty-four healthy subjects. Most notably, the grey matter water content decreases at a rate of 0.034%/vear for females between the 3rd and 8th decade of life, whilst a much stronger decrease is observed in males which sets in after the 5th decade of life. In addition, female grey matter water content is, on average, 1.2% higher than the respective male grey matter water content. In contrast to the heterogeneity observed in grey matter, no significant physiological variation was observed for white matter water content. In addition to absolute grey matter water content, characteristic age- and gender-specific variations were also observed in most of the other variables. To check the potential loss of information associated with the large reduction of the dimensionality of the dataset to 22 parameters only, the age and gender of each individual subject were predicted by employing robust linear discriminant analysis based on only the determined twenty-two variables. The median deviation between predicted and real age was 6.3 years resulting in a high correlation coefficient between both values (r = 0.69). Gender is correctly predicted i

关键词： Adult Aged Aging/physiology Automation Body Water/physiology Brain Chemistry/physiology Brain Mapping/methods Brain Mapping/methods Female Humans image processing, computer-assisted Magnetic Resonance Imaging Male Middle Aged Multivariate Analysis Reference Values Regression Analysis Sex Characteristics

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Longitudinal stability of MRI for mapping brain change using tensor-based morphometry

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NEUROimage 2006年第2期31卷 627-640页

作者： Leow, Alex D. Klunder, Andrea D. Jack, Clifford R., Jr. Toga, Arthur W. Dale, Anders M. Bernstein, Matt A. Britson, Paula J. Gunter, Jefftey L. Ward, Chadwick P. Whitwell, Jennifer L. Borowski, Bret J. Fleisher, Adam S. Fox, Nick C. Harvey, Danielle Kornak, John Schuff, Norbert Studholme, Colin Alexander, Gene E. Weiner, Michael W. Thompson, Paul M. Univ Calif Los Angeles Sch Med Lab Neuro Imaging Brain Mapping DivDept Neurol Los Angeles CA 90095 USA Univ Calif Los Angeles Sch Med Semel Inst Neurosci Los Angeles CA 90095 USA Mayo Clin & Mayo Fdn Coll Med Rochester MN 55905 USA Univ Calif San Diego Dept Neurosci La Jolla CA 92093 USA Univ Calif San Diego Dept Psychiat & Radiol La Jolla CA 92093 USA UCL Inst Neurol London England Univ Calif Davis Sch Med Dept Publ Hlth Sci Davis CA 95616 USA Univ Calif San Francisco Dept Radiol San Francisco CA 94143 USA Univ Calif San Francisco Dept Epidemiol & Biostat San Francisco CA 94143 USA Univ Calif San Francisco Dept Med & Psychiat San Francisco CA 94143 USA Arizona State Univ Dept Psychol Tempe AZ 85287 USA

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance;these maps were then compared using permutation testing. image stability depended on: (1) the pulse sequence;(2) the transmit/receive coil type (birdcage versus phased array);(3) spatial distortion corrections (using MEDIC sequence information);(4) B1-ield intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADN1 project was based on multiple additional image analyses, to be reported elsewhere. (c) 2006 Elsevier Inc. All rights reserved.

关键词： Aged Analysis of Variance Brain/anatomy & histology Brain Mapping/methods Brain Mapping/methods Female Humans image processing, computer-assisted Magnetic Resonance Imaging/methods Male Middle Aged Reference Values Reproducibility of Results

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Anomalous sylvian fissure morphology in Williams syndrome

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NEUROimage 2006年第1期33卷 39-45页

作者： Eckert, Mark A. Galaburda, Albert M. Karchemskiy, Asya Liang, Alyssa Thompson, Paul Dutton, Rebecca A. Lee, Agatha D. Bellugi, Ursula Korenberg, Julie R. Mills, Debra Rose, Fredric E. Reiss, Allan L. Med Univ S Carolina Dept Otolaryngol Head & Neck Surg Charleston SC 29425 USA Harvard Univ Sch Med Dept Neurol Boston MA 02114 USA Stanford Univ Sch Med Dept Psychiat & Behav Sci Stanford CA 94305 USA Univ Calif Los Angeles Sch Med Dept Neurol Los Angeles CA 90095 USA Univ Calif Los Angeles Dept Pediat Los Angeles CA 90095 USA Emory Univ Dept Psychol Atlanta GA 30322 USA

The unusual sensitivity and attraction to auditory stimuli in people with Williams syndrome (WS) has been hypothesized to be the consequence of atypical development of brain regions surrounding the Sylvian fissure. Planum temporale surface area, which is determined in part by Sylvian fissure patterning, was examined in 42 WS and 40 control participants to determine if anomalous Sylvian fissure morphology is present in WS. WS participants had significantly reduced leftward asymmetry of the planum temporale compared to control participants, due to a significant expansion in the size of the right planum temporale. The increased right planum temporale size was largely due to WS participants (24%) who had a right hemisphere Sylvian fissure that coursed horizontally and failed to ascend into the parietal lobe. This sulcal pattern is unusual in the right hemisphere and is more commonly found in the left hemisphere of typically developing individuals. There were no control participants with this type of right hemisphere Sylvian fissure pattern. The right hemisphere Sylvian fissure sulcal patterns were also related to a measure of cortical complexity and the amount of right hemisphere occipital lobe volume, suggesting that intrinsic genetic influences leading to anomalous visual system development in WS have widespread influences on cortical morphology that are similar in manner to extrinsic embryonic visual system lesions. (c) 2006 Elsevier Inc. All rights reserved.

关键词： Adult Cerebral Cortex/pathology Female Fractals Functional Laterality/physiology Humans image processing, computer-assisted In Situ Hybridization, Fluorescence In Situ Hybridization, Fluorescence Magnetic Resonance Imaging Male Occipital Lobe/pathology Temporal Lobe/pathology Williams Syndrome/pathology

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Neural correlates of social and nonsocial emotions: An fMRI study

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NEUROimage 2006年第1期31卷 397-409页

作者： Britton, Jennifer C. Phan, K. Luan Taylor, Stephan F. Welsh, Robert C. Berridge, Kent C. Liberzon, I. Univ Michigan Program Neurosci Ann Arbor MI 48109 USA Univ Chicago Dept Psychiat Chicago IL 60637 USA Univ Michigan Dept Psychiat Ann Arbor MI 48109 USA Univ Michigan Dept Radiol Ann Arbor MI 48109 USA Univ Michigan Dept Psychol Ann Arbor MI 48109 USA

Common theories of emotion emphasize valence and arousal dimensions or alternatively, specific emotions, and the search for the underlying neurocircuitry is underway. However, it is likely that other important dimensions for emotional neurocircuitry exist, and one of them is sociality. A social dimension may code whether emotions are addressing an individual's biological/visceral need versus more remote social goals involving semantic meaning or intentionality. Thus, for practical purposes, social emotions may be distinguished from nonsocial emotions based in part on the presence of human forms. In the current fMRI study, we aimed to compare regional coding of the sociality dimension of emotion (nonsocial versus social) versus the valence dimension of emotion (positive versus negative). Using a novel fMRI paradigm, film and picture stimuli were combined to induce and maintain four emotions varying along social and valence dimensions. Nonsocial emotions of positively valenced appetite and negatively valenced disgust and social emotions of positively valenced joy/ amusement and negatively valenced sadness were studied. All conditions activated the thalamus. Appetite and disgust activated posterior insula and visual cortex, whereas joy/amusement and sadness activated extended amygdala, superior temporal gyrus, hippocampus, and posterior cingulate. Activations within the anterior cingulate, nucleus accumbens, orbitofrontal cortex, and amygdala were modulated by both social and valence dimensions. Overall, these findings highlight that sociality has a key role in processing emotional valence, which may have implications for patient populations with social and emotional deficits. (c) 2005 Elsevier Inc. All rights reserved.

关键词： Adult Attention/physiology Brain/physiology Brain Mapping Brain Mapping Emotions/physiology Female Humans image processing, computer-assisted Magnetic Resonance Imaging Male Nerve Net/physiology Pattern Recognition, Visual/physiology Reaction Time/physiology Social Behavior Social Environment Statistics as Topic

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Molecular architecture and conformational flexibility of human RNA polymerase II

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STRUCTURE 2006年第11期14卷 1691-1700页

作者： Kostek, Seth A. Grob, Patricia De Carlo, Sacha Lipscomb, J. Slaton Garczarek, Florian Nogales, Eva Univ Calif Berkeley Mol & Cell Biol Dept Berkeley CA 94720 USA Howard Hughes Med Inst Berkeley CA 94720 USA Lawrence Berkeley Natl Lab Berkeley CA 94720 USA

Transcription by RNA polymerase II (RNAPII) is a central process in eukaryotic gene regulation. While atomic details exist for the yeast RNAPII, characterization of the human complex lags behind, mostly due to the inability to obtain large quantities of purified material. Although the complexes have the same protein composition and high sequence similarity, understanding of transcription and of transcription-coupled DNA repair (TCR) in humans will require the use of human proteins in structural studies. We have used cryo-electron microscopy, image reconstruction, and variance analysis to characterize the structure and dynamics of human RNAPII (hRNAPII). Our studies show that hRNAPII in solution parallels the conformational flexibility of the yeast structures crystallized in different states but also illustrate a more extensive conformational range with potential biological significance. This hRNAPII study will serve as a structural platform to build up higher-order transcription and TCR complexes and to gain information that may be unique to the human RNAPII system.

关键词： Cryoelectron Microscopy Fungal Proteins/chemistry Hela Cells Humans image processing, computer-assisted Imaging, Three-Dimensional Microscopy, Electron Models, Molecular Molecular Conformation Protein Conformation RNA Polymerase II/chemistry Transcription, Genetic

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Abnormalities of hippocampal surface structure in very mild dementia of the Alzheimer type

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NEUROimage 2006年第1期30卷 52-60页

作者： Wang, L Miller, JP Gado, MH McKeel, DW Rothermich, M Miller, MI Morris, JC Csernansky, JG Washington Univ Sch Med Alzheimers Dis Res Ctr St Louis MO 63110 USA Washington Univ Sch Med Dept Psychiat St Louis MO 63110 USA Washington Univ Sch Med Dept Neurol St Louis MO 63110 USA Washington Univ Sch Med Dept Anat & Neurobiol St Louis MO 63110 USA Washington Univ Sch Med Dept Radiol St Louis MO 63110 USA Washington Univ Sch Med Dept Pathol & Immunol St Louis MO 63110 USA Washington Univ Sch Med Dept Biostat St Louis MO 63110 USA Johns Hopkins Univ Whiting Sch Engn Ctr Imaging Sci Baltimore MD 21218 USA

To better define the pattern of hippocampal deformity early in the course of Alzheimer's disease, we compared the pattern of hippocampal surface variation in subjects with very mild dementia of the Alzheimer type (DAT) and nondemented subjects. The surface of the hippocampus was divided a priori on a neuroanatomical template into three zones approximating the locations of underlying subfields [Csernansky, J.G., Wang, L., Swank, J., Miller, J.P., Gado, M., McKeel, D., Miller, M.I., Morris, J.C., 2005. Preclinical detection of Alzheimer's disease: hippocampal shape and volume predict dementia onset in the elderly. Neuroimage 25, 783-7921];i.e., a lateral zone (LZ) approximating the CA1 subfield, a superior zone (SZ) approximating the combined CA2, CA3, CA4 subfields and the gyrus dentatus (GD), and an interior-medial zone (IMZ) approximating the subiculum. Large-deformation high-dimensional brain mapping (HDBM-LD) was used to generate the hippocampal surfaces of all subjects and to register the surface zones across subjects. Average variations within each zone were calculated for the subjects with very mild DAT as compared to the average of the nondemented subjects. After correcting for multiple comparisons, the very mild DAT subjects showed significant inward variation in the left and right LZ, the left and right IMZ, but not in the left and right SZ as compared to nondemented subjects. In logistic regression analyses, inward variation of the left and right LZ or IMZ by 0.1 mm relative to the average of the nondemented subjects increased the odds of the subject being a very mild DAT subject (range-1.18 to 1.57) rather than being a nondemented subject. The odds ratios for the left and right SZ were not significant. These results represent a replication of our previous findings [Csernansky, J.G., Wang, L., Joshi, S., Miller, J.P., Gado, M., Kido, D., McKeel, D., Morris, J.C., Miller, M.I., 2000. Early DAT is distinguished from aging by high-dimensional mapping of the h

关键词： Activities of Daily Living/classification Age Factors Aged Aged, 80 and over Alzheimer Disease/classification Alzheimer Disease/diagnosis Alzheimer Disease/pathology Brain Mapping Brain Mapping Dominance, Cerebral/physiology Female Hippocampus/pathology Humans image Enhancement image processing, computer-assisted Longitudinal Studies Magnetic Resonance Imaging Male Middle Aged Neuropsychological Tests/statistics & numerical data Prognosis Psychometrics/statistics & numerical data Reference Values Statistics as Topic

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Enhancing BOLD response in the auditory system by neurophysiologically tuned fMRI sequence

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NEUROimage 2006年第3期29卷 1013-1022页

作者： Seifritz, E Di Salle, F Esposito, F Herdener, M Neuhoff, JG Scheffler, K Univ Bern Univ Hosp Clin Psychiat CH-3000 Bern Switzerland Univ Basel Dept Psychiat CH-4025 Basel Switzerland Univ Pisa Dept Neurosci I-56126 Pisa Italy Univ Naples Federico II Dept Neurol Sci I-80127 Naples Italy Coll Wooster Dept Psychol Wooster OH 44691 USA Univ Basel Dept Med Radiol MR Phys CH-4031 Basel Switzerland

Auditory neuroscience has not tapped fMRI's full potential because of acoustic scanner noise emitted by the gradient switches of conventional echoplanar fMRI sequences. The scanner noise is pulsed, and auditory cortex is particularly sensitive to pulsed sounds. Current fMRI approaches to avoid stimulus-noise interactions are temporally inefficient. Since the sustained BOLD response to pulsed sounds decreases with repetition rate and becomes minimal with impulsed sounds, we developed an fMRI sequence emitting continuous rather than pulsed gradient sound by implementing a novel quasi-continuous gradient switch pattern. Compared to conventional fMRI, continuous-sound fMRI reduced auditory cortex BOLD baseline and increased BOLD amplitude with graded sound stimuli, short sound events, and sounds as complex as orchestra music with preserved temporal resolution. Response in subcortical auditory nuclei was enhanced, but not the response to light in visual cortex. Finally, tonotopic mapping using continuous-sound fMRI demonstrates that enhanced functional signal-to-noise in BOLD response translates into improved spatial separability of specific sound representations. (c) 2005 Elsevier Inc. All rights reserved.

关键词： Acoustic Stimulation Auditory Cortex/physiology Auditory Pathways/physiology Brain Mapping Brain Mapping Cerebrovascular Circulation Echo-Planar Imaging Evoked Potentials, Auditory/physiology Humans image processing, computer-assisted Magnetic Resonance Imaging Music Noise Noise Oxygen/blood Photic Stimulation

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