Neuroscience
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Stressful and emotionally arousing experiences are remembered, and previous reports show that repeated exposure to stressful condition enhances emotional learning. However, the usefulness of the repeated exposure depends on the intensity and duration. Although repeated training as a strategy to improve memory performance is receiving increased attention from researchers, repeated training may induce stressful effects that have not yet been considered. ⋯ Following extensive exposure, a negative impact on emotional memory was observed compared with the limited exposure group. A lack of any further improvement in memory function following extensive training exposure was supported by increased corticosterone levels, decreased 5-hydroxytryptamine (5-HT) levels and abnormal oxidative stress levels, which may induce negative effects on memory consolidation. It is suggested that limited exposure to repetitive learning trials is more useful for studying improvement in emotional memory, whereas extensive exposure may produce chronic stress-like condition that can be detrimental and responsible for compromised memory performance.
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Magnetic stimulation is widely used in neuroscience research and clinical treatment. Despite recent progress in understanding the neural modulation mechanism of conventional magnetic stimulation methods, the physiological mechanism at the cortical microcircuit level is not well understood due to the poor stimulation focality and large electric artifact in the recording. To overcome these issues, we used a sub-millimeter-sized coil (micro-coil) to stimulate the mouse auditory cortex in vivo. ⋯ The activated cortical area was dependent on the coil orientation, providing useful information on the effective position of the coil relative to the brain surface for modulating cortical circuitry activity. In addition, numerical calculation of the induced electric field in the brain revealed that the inhomogeneity of the horizontal electric field to the surface is critical for micro-coil-induced cortical activation. The results suggest that our micro-coil technique has the potential to be used as a chronic, less-invasive and highly focal neuro-stimulator, and is useful for investigating microcircuit responses to magnetic stimulation for clinical treatment.
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Subtle semantic deficits can be observed in Alzheimer's disease (AD) patients even in the early stages of the illness. In this work, we tested the hypothesis that the semantic control network is deregulated in mild AD patients. We assessed the integrity of the semantic control system using resting-state functional magnetic resonance imaging in a cohort of patients with mild AD (n = 38; mean mini-mental state examination = 20.5) and in a group of age-matched healthy controls (n = 19). ⋯ Using whole-brain seed-based analysis, we demonstrated that these two regions have altered FC even beyond the semantic control network. In particular, the pMTG displayed a wide-distributed pattern of lower connectivity to several brain regions involved in language-semantic processing, along with a possibly compensatory higher connectivity to the Wernicke's area. We conclude that in mild AD brain regions belonging to the semantic control network are abnormally connected not only within the network, but also to other areas known to be critical for language processing.
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DYT1 dystonia is a neurological disease caused by dominant mutations in the TOR1A gene, encoding for the endoplasmic reticulum (ER)-resident protein torsinA. Recent reports linked expression of the DYT1-causing protein with dysregulation of eIF2α, a key component of the cellular response to ER stress known as the unfolded protein response (UPR). However, the response of the DYT1 mammalian brain to acute ER stress inducers has not been evaluated in vivo. ⋯ Finally, an unbiased RNA-Seq-based transcriptomic analysis of embryonic brain tissue in heterozygous and homozygous DYT1 knockin mice confirmed the presence of eIF2α dysregulation in the DYT1 brain. In sum, these findings support previous reports linking torsinA function, eIF2α signaling and the neuronal response to ER stress in vivo. Furthermore, we describe novel protocols to investigate neuronal ER stress in cultured neurons and in vivo.
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DEK, a chromatin-remodeling gene expressed in most human tissues, is known for its role in cancer biology and autoimmune diseases. DEK depletion in vitro reduces cellular proliferation, induces DNA damage subsequently leading to apoptosis, and down-regulates canonical Wnt/β-catenin signaling, a molecular pathway essential for learning and memory. Despite a recognized role in cancer (non-neuronal) cells, DEK expression and function is not well characterized in the central nervous system. ⋯ Of note, compared to males, females had significantly higher DEK immunoreactivity in the CA1, indicating a sex difference in this region. DEK was co-expressed with neuronal and microglial markers in the CA1 and DG, whereas only a small percentage of DEK cells were in apposition to astrocytes in these areas. Given the reported inverse cellular and molecular profiles (e.g., cell survival, Wnt pathway) between cancer and Alzheimer's disease, these findings suggest a potentially important role of DEK in cognition.