Neuroscience
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Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. ⋯ Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process.
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Recent studies have revealed that the ventral premotor cortex (PMv) of nonhuman primates plays a pivotal role in various behaviors that require the transformation of sensory cues to appropriate actions. Examples include decision-making based on various sensory cues, preparation for upcoming motor behavior, adaptive sensorimotor transformation, and the generation of motor commands using rapid sensory feedback. Although the PMv has frequently been regarded as a single entity, it can be divided into at least five functionally distinct regions: F4, a dorsal convexity region immediately rostral to the primary motor cortex (M1); F5p, a cortical region immediately rostral to F4, lying within the arcuate sulcus; F5c, a ventral convexity region rostral to F4; and F5a, located in the caudal bank of the arcuate sulcus inferior limb lateral to F5p. ⋯ F5p contains "mirror neurons" to understand others' actions based on visual and other types of information, and F4d and F5p work together as a functional complex involved in controlling forelimb and eye movements, most efficiently in the execution and completion of coordinated eye-hand movements for reaching and grasping under visual guidance. In contrast, F5c and F5a are hierarchically higher than the F4d, F5p, and F5v complexes, and play a role in decision-making based on various sensory discriminations. Hence, the PMv subregions form a hierarchically organized integral system from decision-making to eye-hand coordination under various behavioral circumstances.
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A major regulatory task of the organism is to keep brain functions relatively constant in spite of metabolic changes (e.g., hunger vs. satiety) or availability of energy (e.g., glucose administration). Resting-state functional magnetic resonance imaging (rs-fMRI) can reveal resulting changes in brain function but previous studies have focused mostly on the hypothalamus. Therefore, we took a whole-brain approach and examined 24 healthy normal-weight men once after 36 h of fasting and once in a satiated state (six meals over the course of 36 h). ⋯ This interaction was driven by a fALFF increase after glucose treatment in the hunger relative to the satiety condition. Our results indicate that fALFF analysis is the most sensitive measure to detect effects of metabolic states on resting-state brain activity. Moreover, we show that multimethod rs-fMRI provides an unbiased approach to identify spontaneous brain activity associated with changes in homeostasis and caloric intake.
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Clinical patients in a vegetative state or unresponsive wakefulness syndrome (VS/UWS) demonstrate distinct arousal-awareness dissociation; the neuropathological mechanisms underlying such dissociation remain poorly understood. Here, we systematically examined how functional connectivity from the brainstem areas regulating arousal to the cortical networks supporting internal and external awareness is disrupted in minimally conscious state (MCS) and VS/UWS patients. Resting-state functional imaging was conducted in 23 MCS patients, 31 VS/UWS patients, and 20 age-matched healthy individuals. ⋯ We show that functional connectivity from the PTA and caudal midbrain area to the cortical-awareness-supporting networks were significantly reduced in MCS and VS/UWS patients; importantly, as the clinical symptoms of consciousness disorders deepen from MCS to VS/UWS, functional connectivity strength became significantly reduced, changing from presenting no significant connections in MCS to widespread negative connections in VS/UWS. Additionally, we observed increased connectivity from the PTA and caudal midbrain area to limbic structures, the brainstem areas, and the cerebellum in MCS and VS/UWS patients, consistent with prior studies. These findings offer important insights into the neural network mechanisms underlying the long-observed arousal-awareness dissociation in VS/UWS patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.
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The biological effects of the transcription factor NF-E2-related factor 2 (Nrf2) in acute peripheral nervous system (PNS) injury have not been adequately elucidated. By analyzing the results of Nrf2 knockout and Nrf2 activation experiments, we found the following: (1) the antioxidant system was rapidly inactivated after acute PNS injury in a partly Nrf2-dependent manner, giving rise to a temporary state of oxidative stress, and then slowly and partially recovered following regeneration. (2) Nrf2 knockout promoted the reprogramming and proliferation of Schwann cells and inhibited myelination, as well as the redifferentiation of repair Schwann cells. (3) Dimethyl fumarate had no influence on the myelination of regenerated nerves. (4) Nrf2 functional regulation was able to regulate the redox status of nerves by changing the levels of target antioxidants and reactive oxygen species (ROS) at the same time, without altering the balance between them. In conclusion, the Nrf2-antioxidant system was temporarily inactivated in injured nerves, promoting Schwann cell reprogramming and proliferation, and its functional recovery was essential for Schwann cell redifferentiation and myelination.