Biomedical subjects

Sooyoung Chung

Publications and source records attributed to Sooyoung Chung.

11 recordsLinked to original sources

PubMed2006

Hyperactivity and alteration of the midbrain dopaminergic system in maternally stressed male mice offspring.

We recently demonstrated that prolonged maternal stress produces profound and long-lasting deficits in brain functions by programming a subset of target genes. We have now examined the possible effects of prenatal stress on the motility of adult offspring and dopamine (DA)-related gene expression in their midbrains, one of the target brain regions of stress hormones. Maternally stressed adult male mice showed impaired response habituation to novelty, and increased wheel-running activity associated with altered responses to DA receptor and DA transporter (DAT) blockers. Along with the behavioral changes, the expression profiles of several genes of the midbrain DAergic system appeared to be altered. Expression of DAT was reduced and expression of DA receptors and striatal DA-regulated neuropeptide genes was also affected. Taken together, the present findings indicate that maternal stress can cause hyperactivity in adult offspring associated with alterations in the midbrain DAergic system suggestive of a functional hyperdopaminergic state.

Adaptation, Physiological↗

PubMed2006

Highly ordered arrangement of single neurons in orientation pinwheels.

In the visual cortex of higher mammals, neurons are arranged across the cortical surface in an orderly map of preferred stimulus orientations. This map contains 'orientation pinwheels', structures that are arranged like the spokes of a wheel such that orientation changes continuously around a centre. Conventional optical imaging first demonstrated these pinwheels, but the technique lacked the spatial resolution to determine the response properties and arrangement of cells near pinwheel centres. Electrophysiological recordings later demonstrated sharply selective neurons near pinwheel centres, but it remained unclear whether they were arranged randomly or in an orderly fashion. Here we use two-photon calcium imaging in vivo to determine the microstructure of pinwheel centres in cat visual cortex with single-cell resolution. We find that pinwheel centres are highly ordered: neurons selective to different orientations are clearly segregated even in the very centre. Thus, pinwheel centres truly represent singularities in the cortical map. This highly ordered arrangement at the level of single cells suggests great precision in the development of cortical circuits underlying orientation selectivity.

Animals↗

PubMed2006

Lack of patchy horizontal connectivity in primary visual cortex of a mammal without orientation maps.

In the cerebral cortex of mammals, horizontal connections link cells up to several millimeters apart. In primary visual cortex (V1) of mammals with orientation maps, horizontal connections ramify in periodic patches across the cortical surface, connecting cells with similar orientation preferences. Rodents have orientation-selective cells but lack orientation maps, raising questions about relationships of horizontal connections to functional maps and receptive field properties. To address these questions, we studied anatomy of horizontal connections and characterized horizontal functional interactions in V1 of the gray squirrel, a highly visual rodent. Long-range intrinsic connections in squirrel V1 extended 1-2 mm but were not patchy or periodic. This result suggests that periodic and patchy connectivity is not a universal organizing principle of cortex, and the existence of patchy and periodic connectivity and functional maps may be linked. In multielectrode and intracellular recordings, we found evidence of unselective local interactions among cells, similar to pinwheel centers of carnivores. These data suggest that, in mammals with and without orientation maps, local connections link near neighbors without regard to orientation selectivity. In single-unit recordings, we found length-summing and end-stopped cells that were similar to those in other mammals. Length-summing cell surrounds were orientation selective, whereas surrounds of end-stopped cells were not. Receptive field response classes are quite similar across mammals, and therefore patchy and columnar connectivity may not be essential for these properties.

Animals↗

PubMed2006

Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity.

Stress in adulthood can have a profound effect on physiology and behavior, but the extent to which prolonged maternal stress affects the brain function of offspring when they are adult remains primarily unknown. In the present work, chronic immobilization stress to pregnant mice affected fetal growth and development. When pups born from stressed mice were reared to adulthood in an environment identical to that of nonstressed controls, several physiological parameters were essentially unaltered. However, spatial learning and memory was significantly impaired in the maternally stressed offspring in adulthood. Furthermore, electrophysiological examination revealed a significant reduction in NMDA receptor-mediated long-term potentiation in the CA1 area of hippocampal slices. Subsequent biochemical analysis demonstrated a substantial decrease in NR1 and NR2B subunits of the NMDA receptor in synapses of the hippocampus, and the interaction between these two subunits appeared to be reduced. These results suggest that prolonged maternal stress leads to long-lasting malfunction of the hippocampus, which extends to and is manifested in adulthood.

Animals↗

PubMed2005

A protective role of 27-kDa heat shock protein in glucocorticoid-evoked apoptotic cell death of hippocampal progenitor cells.

Hippocampus is one of the most vulnerable tissues to glucocorticoid (GC). In the present study, we demonstrate that dexamethasone (DEX), a synthetic GC, induces apoptotic cell death in hippocampal progenitor HiB5 cells without any additional insult. Interestingly, expression of 27-kDa heat shock protein (HSP27) was markedly induced by DEX in time- and dose-dependent manners. This induction was dependent on the production of reactive oxygen species (ROS), suggesting that DEX-evoked oxidative damage to HiB5 cells is responsible for the HSP27 induction. To evaluate a possible role of HSP27, we generated two mutant HiB5 cell lines, in which expression of HSP27 was inhibited or enhanced by the over-expression of HSP27 cDNA with antisense or sense orientation (AS-HSP27 and S-HSP27, respectively). DEX-induced apoptotic cell population was significantly increased in AS-HSP27 HiB5 cells and evidently decreased in S-HSP27 cells. These results indicate that HSP27 protects hippocampal progenitor cells from GC-induced apoptotic cell death.

Animals↗

PubMed2005

Cooperative actions of Tra2alpha with 9G8 and SRp30c in the RNA splicing of the gonadotropin-releasing hormone gene transcript.

In earlier studies, we demonstrated that excision of the first intron (intron A) from the gonadotropin-releasing hormone (GnRH) transcript is highly cell type- and developmental stage-specific. The removal of GnRH intron A requires exonic splicing enhancers on exons 3 and 4 (ESE3 and ESE4, respectively). Tra2alpha,a serine/arginine-rich (SR)-like protein, specifically binds to ESE4, although it requires additional nuclear co-factors for efficient removal of this intron. In the present study, we demonstrate the cooperative action of multiple SR proteins in the regulation of GnRH pre-mRNA splicing. SRp30c specifically binds to both ESE3 and ESE4, whereas 9G8 binds to an element in exon 3 and strongly enhances the excision of GnRH intron A in the presence of minimal amount of other nuclear components. Interestingly, Tra2alpha can interact with either 9G8 or SRp30c, whereas no interaction between 9G8 and SRp30c is observed. Tra2alpha has an additive effect on the RNA binding of these proteins. Overexpression or knock-down of these three proteins in cultured cells further suggests their essential role in intron A excision activities, and their presence in GnRH neurons of the mouse preoptic area further strengthens this possibility. Together, these results indicate that interaction of Tra2alpha with 9G8 and SRp30c appears to be crucial for ESE-dependent GnRH pre-mRNA splicing, allowing efficient generation of mature mRNA in GnRH-producing cells.

Animals↗

PubMed2005

Differential adaptive responses to chronic stress of maternally stressed male mice offspring.

It is well established that stress in early life can alter the activity of the hypothalamus-pituitary-adrenal (HPA) axis, but most studies to date have focused on HPA reactivity in response to a single acute stress. The present study addressed whether stress in pregnant mice could influence the adaptive responses of their offspring to chronic stress. Male offspring were exclusively used in this study. Elevated plus maze tests revealed that 14 d of repeated restraint stress (6 h per day; from postnatal d 50-63) significantly increased anxiety-like behavior in maternally stressed mice. NBI 27914, a CRH receptor antagonist, completely eliminated anxiety-related behaviors in a dose-dependent manner, indicating an involvement of a hyperactive CRH system. In accordance with increased anxiety, CRH contents in the hypothalamus and amygdala were significantly higher in these mice. Despite an increased basal activity of the CRH-ACTH system, the combination of chronic prenatal and postnatal stress resulted in a significant reduction of basal plasma corticosterone level, presumably because of a defect in adrenal function. Along with alterations in hypothalamic and hippocampal corticosteroid receptors, it was also demonstrated that a dysfunction in negative feedback inhibition of the HPA axis could be deteriorated by chronic stress in maternally stressed male mice. Taken together, these results indicate that exposure to maternal stress in the womb can affect an animal's coping capacity to chronic postnatal stress.

Adaptation, Psychological↗

PubMed2005

Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex.

Neurons in the cerebral cortex are organized into anatomical columns, with ensembles of cells arranged from the surface to the white matter. Within a column, neurons often share functional properties, such as selectivity for stimulus orientation; columns with distinct properties, such as different preferred orientations, tile the cortical surface in orderly patterns. This functional architecture was discovered with the relatively sparse sampling of microelectrode recordings. Optical imaging of membrane voltage or metabolic activity elucidated the overall geometry of functional maps, but is averaged over many cells (resolution >100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.

Analysis of Variance↗

PubMed2005

Orientation selectivity without orientation maps in visual cortex of a highly visual mammal.

In mammalian neocortex, the orderly arrangement of columns of neurons is thought to be a fundamental organizing principle. In primary visual cortex (V1), neurons respond preferentially to bars of a particular orientation, and, in many mammals, these orientation-selective cells are arranged in a semiregular, smoothly varying map across the cortical surface. Curiously, orientation maps have not been found in rodents or lagomorphs. To explore whether this lack of organization in previously studied rodents could be attributable to low visual acuity, poorly differentiated visual brain areas, or small absolute V1 size, we examined V1 organization of a larger, highly visual rodent, the gray squirrel. Using intrinsic signal optical imaging and single-cell recordings, we found no evidence of an orientation map, suggesting that formation of orientation maps depends on mechanisms not found in rodents. We did find robust orientation tuning of single cells, and this tuning was invariant to stimulus contrast. Therefore, it seems unlikely that orientation maps are important for orientation tuning or its contrast invariance in V1. In vertical electrode penetrations, we found little evidence for columnar organization of orientation-selective neurons and little evidence for local anisotropy of orientation preferences. We conclude that an orderly and columnar arrangement of functional response properties is not a universal characteristic of cortical architecture.

Action Potentials↗

PubMed2004

Comparison of a new lateral-flow chromatographic membrane immunoassay to viral culture for rapid detection and differentiation of influenza A and B viruses in respiratory specimens.

The performance of a new rapid lateral-flow chromatographic membrane immunoassay test kit for detection of influenza virus was evaluated and compared to that of viral culture in respiratory secretions collected from 400 adults and children seen at three large university hospitals during the recent 2003 influenza season. The rapid test provided results in 15 min, with excellent overall performance statistics (sensitivity, 94.4%; specificity, 100%; positive predictive value, 100%; negative predictive value, 97.5%). Both influenza A and B type viruses were reliably detected, with no significant difference in performance statistics noted by influenza virus type or by the center performing the test.

Chromatography↗

PubMed2002

Short-term depression at thalamocortical synapses contributes to rapid adaptation of cortical sensory responses in vivo.

In vivo whole-cell recordings revealed that during repeated stimulation, synaptic responses to deflection of facial whiskers rapidly adapt. Extracellular recordings in the somatosensory thalamus revealed that part of the adaptation occurs subcortically, but because cortical adaptation is stronger and recovers more slowly, cortical mechanisms must also contribute. Trains of sensory stimuli that produce profound sensory adaptation did not alter intrinsic membrane properties, including resting membrane potential, input resistance, and current-evoked firing. Synaptic input evoked via intracortical stimulation was also unchanged; however, synaptic input from the somatosensory thalamus was depressed by sensory stimulation, and this depression recovered with a time course matching that of the recovery of sensory responsiveness. These data strongly suggest that synaptic depression of thalamic input to the cortex contributes to the dynamic regulation of neuronal sensitivity during rapid changes in sensory input.

Adaptation, Physiological↗