Neuroscience
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Depression is a serious physical and mental disease, with major depressive disorder (MDD) being a hard-to-treat, life-threatening form of the condition. Currently, esketamine (ESK) is used in the clinical treatment of MDD, but the drug mechanisms continue to be unclear. In this study, we explored the therapeutic efficacy of ESK against lipopolysaccharide (LPS)-induced neuroinflammatory, autophagic, and depressive symptoms and the possible mechanisms behind them. ⋯ Furthermore, we were interested to know if ESK in combination with other autophagy inhibitors would have a better antidepressant effect, and we chose the autophagy inhibitor 3-MA for this attempt. Interestingly, the use of 3-MA did not attenuate or even enhance the therapeutic effect of ESK. The results suggest that, in the LPS-induced depression models, ESK conveyed an antidepressant effect via the inhibition of autophagy through the mTOR-BDNF pathway.
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Previous experiences can drive adaptive behavior based on different characteristics, including contextual ones. Indeed, contextual information can be used as a criterion to guide the recall of the most relevant memory trace and the inhibition of others. The medial Prefontal Cortex (mPFC) has been proposed as an area that plays a pivotal role in regulating the retrieval of memory traces in downstream regions. ⋯ We also found an increase in c-Fos expression in the mPFC after mPFC 5-HT2aR blockade that does not correlate with the animals' behavioral response. However, these changes showed a significant correlation with those observed in the PRH. These results suggest that mPFC 5-HT2aR signaling may modulate the behavioral response during memory recall by controlling the neuronal activation in the PRH.
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Transcranial direct current stimulation (tDCS) has been used to explore the causal relationship between specific brain regions and task switching. However, most studies have focused on the frontal cortex, and only few have examined other related cortices, e.g., the parietal cortex. However, no prior study has systematically explored the tDCS-induced effect of the parietal cortex in different task switching types. ⋯ It was noted that compared with sham group, significantly higher switch cost reaction time of right anode tDCS (RA) group was found in predictable task but not unpredictable task. No interaction effect was observed between congruence and tDCS groups in predictable task. These findings suggested that a-tDCS over right parietal cortex could markedly decrease the predictable task-switching performance in both congruent and incongruent trials, and indicated that parietal cortex is more likely to be involved in the proactive cognitive processes, such as endogenous preparation.
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The present study examined whether tactile perception of the fingertip modulates excitability of the motor cortex supplying the intrinsic hand muscle and whether this modulation is specific to the fingertip stimulated and the muscle and hand tested. Tactile stimulation was given to one of the five fingertips in the left or right hand, and transcranial magnetic stimulation eliciting motor evoked potential in the first dorsal interosseous muscle (FDI) or abductor digiti minimi was given 200 ms after the onset of tactile stimulation. The corticospinal excitability of the FDI at rest was suppressed by the tactile stimulation of the right middle fingertip, but such suppression was absent for the other fingers stimulated and for the other muscle or hand tested. ⋯ These findings indicate that tactile perception of the right middle fingertip suppresses excitability of the motor cortex supplying the right FDI at rest. The suppression of corticospinal excitability was absent during tonic contraction of the right FDI, indicating that the motor execution process interrupts the tactile perception-induced suppression of motor cortical excitability supplying the right FDI. These findings are in line with a view that the tactile perception of the right middle finger induces surround inhibition of the motor cortex supplying the prime mover of the finger neighboring the stimulated finger.