Neuroscience
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Recent genome-wide association studies (GWAS) have found cerebellum as a top hit for sleep regulation. Restless legs syndrome (RLS) is a sleep-related sensorimotor disorder characterized by uncomfortable sensations in the extremities, generally at night, which are often relieved by movements. Clinical studies have found that RLS patients have structural and functional abnormalities in the cerebellum. ⋯ Btbd9 pKO mice also had an increased probability of waking at rest. Unlike the Btbd9 knockout mice, there was no increased thermal sensation in the Btbd9 pKO. Our results indicate that the Btbd9 knockout influences the PC activity; dysfunction in the cerebellum may contribute to the motor restlessness found in the Btbd9 knockout mice.
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Parkinson's disease is a disorder of adult onset involving the progressive degeneration of selective portions of the central nervous system. It is known that mitochondrial dysfunction is involved in the pathogenesis of PD. Given that PGC-1α induces proliferation of mitochondria via transcription regulation, it is possible that PGC-1α pathway dysregulation is involved in PD pathogenesis. ⋯ Expression of CoxIV, SDHA and Tomm20 also significantly decreased in the ventral midbrains of 10-month-old PGC-1α null mice. Thus, PGC-1α KO in mice induced dopaminergic neuron degeneration in the SNpc and DA deficits in the striatum in an age-dependent manner. Progressive impairment of motor coordination in an age-dependent manner was correlated to the extent of nigrostriatal dopaminergic pathway degeneration and mitochondrial dysfunction.
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Deep brain stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. It acts by altering brain networks and facilitating synaptic plasticity. For enhancing cognitive functions, the central thalamus (CT) has been shown to be a potential DBS target. ⋯ Concurrent with enhanced learning performance, bilateral CT-DBS resulted in alteration in the functional connectivity of brain networks determined by resting-state fMRI. Western blot analyses showed that the protein level of both dopamine D1 and α4-nicotinic acetylcholine receptors was increased, and dopamine D2 receptor was decreased. These data suggest that CT-DBS can enhance cognitive performance as well as brain connectivity through the modulation of synaptic plasticity, such that CT is a target providing high potential for the remediation of acquired cognitive learning and memory disabilities.
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Previous studies have shown that aging is associated with changes in decision behavior. However, the neural mechanisms that underpin such age differences are inadequately understood. In this study, we aim to characterize the optimal neural model underlying a dynamic decision making task in both young and older adults, and further examine the age differences from the perspective of effective connectivity. ⋯ The dynamic causal modeling analysis, with the coupling between the ventromedial prefrontal cortex (VMPFC), dorsolateral prefrontal cortex (DLPFC) and anterior insula (AI) that were identified in our task-related activation and psychophysiological interaction analysis, was performed to address the best fitting neural model and characterize age differences. Although both age groups adopted the same optimal model with bidirectional connection between the VMPFC and DLPFC, older adults exhibited up-regulation in several connections and among which the increased modulatory effect of AI-to-VMPFC subserving their decision quality. Our finding suggests that older adults might utilize different neural strategy via compensation to counteract the impact of advanced age in risk taking process.