Neuroscience
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Neurons and neighboring astrocytic glia are mostly studied in nervous tissues from rodents whereas less is known on their properties and interactions in the human brain. Here, confocal/multiphoton fluorescence imaging for several hours revealed that co-cultured fetal human cortical neurons and astrocytes show pronounced spontaneous rises of cytosolic Ca(2+) which last for up to several minutes without concomitant changes in either movements or membrane potential of mitochondria. Similar Ca(2+) rises were evoked mainly in neurons by bath-applied glutamate or γ-aminobutyric acid (GABA) acting via N-methyl-d-aspartate (NMDA)+AMPA/Kainate and GABAA receptors, respectively. ⋯ During such metabolic perturbation, mitochondrial depolarization also occurred in astrocytes, whereas Ca(2+) was largely unaffected. In summary, fetal human cortical neurons and astrocytes show distinct patterns of neuro/glio-transmitter- and metabolically-evoked Ca(2+) rises and possess active mitochondria. One aspect of our discussion deals with the question of whether the functional mitochondria contribute to cellular Ca(2+) homeostasis that seems to be already well-developed in fetal human cortical brain cells.
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Decades of clinical and basic research indicate significant links between altered hypothalamic-pituitary-adrenal (HPA)-axis hormone dynamics and major depressive disorder (MDD). Recent neuroimaging studies of MDD highlight abnormalities in stress response circuitry regions which play a role in the regulation of the HPA-axes. However, there is a dearth of research examining these systems in parallel, especially as related to potential trait characteristics. ⋯ Compared to controls, rMDD women demonstrated higher anxiety ratings, increased cortisol levels, and hyperactivation in the amygdala and hippocampus, p<0.05, family-wise error (FWE)-corrected in response to the stress challenge. Among rMDD women, amygdala activation was negatively related to cortisol changes and positively associated with the duration of remission. Findings presented here provide evidence for differential effects of altered HPA-axis hormone dynamics on hyperactivity in stress response circuitry regions elicited by a well-validated stress paradigm in women with recurrent MDD in remission.
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Learning from feedback involves a network of various cortical and subcortical regions. Although activation in this network has been shown to be especially strong in successful learners, it is currently unclear which of these regions are related to within-subject variation in learning performance. To this aim, 21 subjects performed a probabilistic feedback-learning task consisting of multiple independent Learning blocks and non-learning Control blocks, while functional magnetic resonance imaging data were acquired. ⋯ Finally, activation only in the ventral striatum was associated with within-subject learning performance across the Learning blocks. Taken together, these latter two results are argued to provide the answer to the main research question: ventral striatum activation is associated with within-subject variations in learning performance. The ventral striatum appears to play a vital role in learning by adjusting behavior based on feedback.
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Persistent exposure to environmental stressors causes dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR) levels throughout the brain. Social subordination in socially housed female rhesus results in distinctive stress-related physiological and behavioral phenotypes that are dependent on the ovarian hormone estradiol (E2). In the present study, we utilized ovariectomized adult female rhesus monkeys undergoing hormone replacement with E2 to test the hypothesis that the chronic psychosocial stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic regions implicated in emotional processing including the prefrontal cortex, temporal lobe (amygdala and hippocampus), and hypothalamus. ⋯ T1-weighted structural magnetic resonance imaging scans were also acquired for PET scan co-registration, in order to perform a region of interest analysis using the pons as a reference region. Compared to socially dominant females, subordinate females exhibited increased GABAAR BPND in the prefrontal cortex but not in the temporal lobe or the hypothalamus. Administration of astressin B eliminated the status difference in GABAAR BPND in the prefrontal cortex, suggesting that the chronic stressor of social subordination modulates GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal regions.
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The neural correlates of perceptual load induced attentional selection were investigated in an functional magnetic resonance imaging (fMRI) experiment in which attentional selection was manipulated through the variation of perceptual load in target search. Participants searched for a vertically or horizontally oriented bar among heterogeneously (the high load condition) or homogeneously (the low load condition) oriented distractor bars in the central display, which was flanked by a vertical or horizontal bar presented at the left or the right periphery. The search reaction times were longer when the central display was of high load than of low load, and were longer when the flanker was incongruent than congruent with the target. ⋯ Anterior cingulate cortex (ACC) was more activated for the incongruent than for the congruent trials. Moreover, ACC and bilateral anterior insula were sensitive to the interaction between perceptual load and flanker congruency such that the activation differences between the incongruent and congruent conditions were significant in the low, but not in the high load condition. These results are consistent with the claim that ACC and bilateral anterior insula may exert executive control by selectively biasing processing in favor of task-relevant information and this biasing depends on the resources currently available to the control system.