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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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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Postural support alters anticipatory postural adjustments (APAs). Efficient adaptation to changes in postural support in reactive and centrally initiated postural synergies is impaired in Parkinson's disease (PD). This study examined whether APAs are affected differently by familiar and novel supports in people with PD, ON and OFF levodopa. ⋯ Controls and PD patients in the OFF state further refined the postural strategy with practice as evidenced by changes in amplitude of vertical ground reaction forces and forces applied to support apparatus within conditions between the initial and final trials. In the ON state, people with PD failed to refine the use of postural supports in any condition. The results suggest that immediate postural adaptation is intact in people with PD and unaffected by levodopa administration but the ability to refine postural adaptations with task experience is compromised by dopamine therapy.
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In the adult CNS, tissue-specific germinal niches, such as the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus of the hippocampus, contain multipotent neural precursor cells (NPCs) with the capacity to self-renew and differentiate into functional brain cells (i.e. neurons, astrocytes or oligodendrocytes). Due to their intrinsic plasticity, NPCs can be considered an essential part of the cellular mechanism(s) by which the CNS tries to repair itself after an injury. In inflammatory CNS disorders, such as multiple sclerosis (MS), neurogenesis and gliogenesis occur as part of an 'intrinsic' self-repair process. ⋯ We found that PPMS derived CSF markedly reduced the proliferation of ENStem-A and increased their differentiation toward neuronal and oligodendroglial cells, compared to control CSF. Similar but less striking results were seen when ENstem-A were treated with SPMS derived CSF. Our findings suggest that in both SPMS and PPMS the CNS milieu, as determined by extrapolation from CSF findings, may stimulate the endogenous pool of NPCs to differentiate into neurons and oligodendrocytes.