Neuroscience
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The Src family kinase (SFK) is a subfamily of non-receptor tyrosine kinases. The SFK member Fyn is enriched at synaptic sites in the limbic reward circuit and plays a pivotal role in the regulation of glutamate receptors. In this study, we investigated changes in phosphorylation and function of the two key SFK members (Fyn and Src) and SFK interactions with a metabotropic glutamate (mGlu) receptor in the limbic striatum of adult rats in response to chronic passive stress, i.e., prolonged social isolation which is a pre-validated animal paradigm modeling depression in adulthood. ⋯ Moreover, social isolation induced an increase in surface expression of striatal mGlu5 receptors, which was reduced by an SFK inhibitor. These results indicate that Fyn interacts with mGlu5 receptors in striatal neurons. Adulthood social isolation in rats enhances the Fyn-mGlu5 interaction, which appears to be critical for the upregulation of surface mGlu5 receptor expression in striatal neurons.
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Alzheimer's disease (AD) is the most prevalent type of dementia affecting older people. The identification of biomarkers is increasingly important and would be crucial for future therapy. ⋯ Finally, we showed that in normal erythrocytes, treated in vitro with Aβ1-42 peptide, both band3 phosphorylation and lyn activation occurs. These results suggest that modulation of tyrosine phosphorylation signaling may be evaluated as a potential peripheral marker in AD.
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The spontaneous action potential of isolated sinoatrial node (SAN) cells is regulated by a coupled-clock system of two clocks: the calcium clock and membrane clock. However, it remains unclear whether calcium clock inhibitors have a direct effect on the membrane clock. The purpose of this study was to investigate the direct effect of cyclopiazonic acid (CPA), a selective calcium clock inhibitor, on the function of the membrane clock of SAN cells. ⋯ These results indicate that the direct inhibition effect of CPA on the If current in SAN cells is both concentration- and time-dependent. The underlying mechanisms may involve slowing down steady-state activation and the downregulation of pacemaker channel protein expression.
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Our choices are often informed by temporally integrating streams of sensory information. This has been well demonstrated in the visual and auditory domains, but the integration of tactile information over time has been less studied. We designed an active touch task in which participants explored a spheroid-shaped object to determine its inclination with respect to the horizontal plane (inclined to the left or the right). ⋯ The behavioral results were fit with a bounded accumulation model and an independent sampling model that assumes no sensory accumulation. The results of model fits favor an accumulation-to-bound mechanism and suggest that participants integrate the first 600 ms of 1800 ms-long stimuli. This means that the somatosensory system benefits from longer streams of information, although it does not make use of all available evidence.
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The human right inferior frontal cortex (IFC) plays a critical role in response inhibition. It has also been demonstrated that the IFC is heterogeneous and that the ventral part of the IFC (vIFC) is more critical to inhibition of prepotent response tendency. Recent areal parcellation analyses based on resting-state functional connectivity have revealed that the right vIFC consists of multiple functional areas. ⋯ Correlations were significantly stronger in the ventral parcel. Moreover, the ventral parcel exhibited a negative correlation between brain activity during response inhibition and stop-signal reaction time (SSRT), a behavioral measure used to evaluate stopping performance. These dissociation results suggest that the ventral region in the vIFC plays a more central role in the brain network by increasing brain activity, which may further predict better performance of response inhibition.