Neuroscience
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The floor plate of the developing midbrain gives rise to dopaminergic (DA) neurons, an important class of cells involved in Parkinson's disease (PD). Neural progenitors of the midbrain floor plate utilize key genes in transcriptional networks to drive dopamine neurogenesis. Identifying factors that promote dopaminergic neuron transcriptional networks can provide insight into strategies for therapies in PD. ⋯ We then showed that overexpression of Nato3 in the developing chick mesencephalon produces a regionally dependent increase in genes associated with the DA neurogenesis, (such as Foxa2, Lmx1b and Shh) as well as DA neuron genes Nurr1 (an immature DA neuron marker) and mRNA expression of tyrosine hydroxylase (TH, a mature DA neuron marker). Interestingly, our data also showed that Nato3 is a potent regulator of Lmx1b by its broad induction of Lmx1b expression in neural progenitors of multiple regions of the CNS, including the midbrain and spinal cord. These data introduce a new, in vivo approach to identifying a gene that can drive DA transcriptional networks and provide the new insight that Nato3 can drive expression of key DA neuron genes, including Lmx1b, in neural progenitors.
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Mid-adulthood represents the critical window period usually associated with the development of age-related diseases. Despite several attempts to delineate the pathological mechanisms underlying postnatal immune challenge and altered brain functions, the role of sex-dependent changes in affective behaviors of middle-aged animals requires more attention. In this study, we sought to investigate behavioral and molecular response patterns at mid-adulthood linked to early-life immune activation. ⋯ Our data further demonstrated a significant increase in microglial complexity and increased levels of tumor necrosis factor (TNFα), nitric oxide (NOx), and lipid peroxidation in the prefrontal cortex of female rats compared to their male counterparts and phosphate-buffered saline (PBS) littermate controls. With these results, we established significant interaction between sex differences and LPS-induced alterations in behavior and associated oxidative and immunohistochemical changes. These findings may provide an insight to better understand the neuroimmunological mechanisms of sex-dependent brain pathological manifestations occurring at mid-adulthood.
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Training inhibitory control, the ability to suppress motor or cognitive processes, not only enhances inhibition processes, but also reduces the perceived value and behaviors toward the stimuli associated with the inhibition goals during the practice. While these findings suggest that inhibitory control training interacts with the aversive and reward systems, the underlying spatio-temporal brain mechanisms remain unclear. We used electrical neuroimaging analyses of event-related potentials to examine the plastic brain modulations induced by training healthy participants to inhibit their responses to rewarding (pleasant chocolate) versus aversive food pictures (unpleasant vegetables) with Go/NoGo tasks. ⋯ The electrophysiological results also revealed an interaction between reward responses and inhibitory control plasticity: we observed different effects of practice on the rewarding vs. aversive NoGo stimuli at 200 ms post-stimulus onset, when the conflicts between automatic response tendency and task demands for response inhibition are processed. Electrical source analyses revealed that this effect was driven by an increase in right orbito-cingulate and a decrease in temporo-parietal activity to the rewarding NoGo stimuli and the reverse pattern to the aversive stimuli. Our collective results provide direct neurophysiological evidence for interactions between stimulus reward value and executive control training, and suggest that changes in the assessment of stimuli with repeated motoric inhibition likely follow from associative learning and behavior-stimulus conflicts reduction mechanisms.
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Loneliness has a strong neurobiological basis reflected by its specific relationships with structural brain connectivity. Critically, affect traits are highly related to loneliness, which shows close association with the onset and severity of major depressive disorder. ⋯ The findings of this study confirmed that both global and average local efficiency negatively mediated the association between low positive affect and high negative affect and loneliness, and the mediation was more sensitive to sibling-shared affect traits. The findings have important implications for interventions targeted at reducing the detrimental impact of familiar negative emotional experiences and loneliness.
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Paired-pulse transcranial magnetic stimulation (ppTMS) has been used extensively to probe local facilitatory and inhibitory function in motor cortex. We previously developed a reliable ppTMS method to investigate these functions in visual cortex and found reduced thresholds for net intracortical inhibition compared to motor cortex. The current study used this method to investigate the temporal dynamics of local facilitatory and inhibitory networks in visual cortex in 28 healthy subjects. ⋯ Intervals of 50-200 ms exhibited statistically significant suppression of phosphenes, however, suppression was not uniform with some subjects demonstrating no change or facilitation. This study demonstrates that the temporal dynamics of local inhibitory and facilitatory networks are different across motor and visual cortex and that optimal parameters to index local inhibitory and facilitatory influences in motor cortex are not necessarily optimal for visual cortex. We refer to the observed inhibition as visual cortex inhibition (VCI) to distinguish it from the phenomenon reported in motor cortex.