Neuroscience
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Sepsis-associated encephalopathy (SAE) is characterized by diffuse cerebral and central nervous system (CNS) dysfunction. Microglia play a vital role in protecting the brain from neuronal damage, which is closely related to inflammatory responses. The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway has an impact on microglial and neuronal injury. ⋯ SAE activated Nrf2 expression, and H2 further improved Nrf2 expression in SAE mice. H2 alleviated microglial polarization from the M1 to the M2 phenotype and cytokine release in the cerebral cortex and improved neuronal injury or cognitive dysfunction in SAE mice and wild-type mice but not in Nrf2-/- mice. H2 exerts antineuroinflammatory effects associated with TLR4/NF-κB signaling activation and neuroprotective effects by inhibiting the excessive release of proinflammatory cytokines, neuronal loss and apoptosis in vitro and in vivo through the Nrf2 pathway.
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Across mammalian species, patterned activity in neural populations is a prominent feature of developing sensory cortices. Numerous studies have long appreciated the diversity of these patterns, characterizing their differences in spatial and temporal dynamics. In the murine somatosensory cortex, neuronal co-activation is thought to guide the formation of sensory maps and prepare the cortex for sensory processing after birth. ⋯ Here, we discuss how emergent synchronous activity across the first postnatal weeks is shaped by underlying gamma aminobutyric acid (GABA)ergic contributors in the somatosensory cortex. Further, the importance of participation in specific activity patterns per se for neuronal maturation and perdurance will be of particular highlight in this survey of recent literature. Finally, we underscore how aberrant neuronal synchrony and disrupted inhibitory interneuron activity underlie sensory perturbations in neurodevelopmental disorders, particularly Autism Spectrum Disorders (ASDs), emphasizing the importance of future investigative approaches that incorporate the spatiotemporal features of patterned activity alongside the cellular components to probe disordered circuit assembly.
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Review
Bioactive Lipid Mediators in the Initiation and Resolution of Inflammation after Spinal Cord Injury.
Neuroinflammation is a prominent feature of the response to CNS trauma. It is also an important hallmark of various neurodegenerative diseases in which inflammation contributes to the progression of pathology. Inflammation in the CNS can contribute to secondary damage and is therefore an excellent therapeutic target for a range of neurological conditions. ⋯ Bioactive lipids constitute a large group of molecules that modulate the initiation and the resolution of inflammation. Dysregulation of these bioactive lipid pathways can lead to excessive acute inflammation, and failure to resolve this by specialized pro-resolution lipid mediators can lead to the development of chronic inflammation. The focus of this review is to discuss the effects of bioactive lipids in spinal cord trauma and their potential for therapies.
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Few studies have identified the intrahemispheric functional connectivity between the ipsilateral dorsal premotor cortex (PMd) and the primary motor hand area (M1hand) due to technical limitations. In this proof-of-concept study, a novel neuronavigated dsTMS set-up was employed, combining stimulation over left PMd and left M1hand using the edge of a butterfly coil and a small cooled-coil. This arrangement was warranted because coil (over)heating and inter coil distance are limiting factors when investigating connectivity between stimulation targets in close proximity and over a longer duration. ⋯ In males, significant inhibition of motor-evoked potentials was identified, whereas females demonstrated a facilitatory effect that did not survive correction for multiple comparisons. E-field simulations revealed that the E-field induced by the coil targeting PMd was maximal in PMd, with weaker E-field strengths extending to regions beyond PMd. Summarizing, the current dsTMS set-up enabled stimulating at an inter-target distance of 35 mm without any indications of coil-overheating.
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To make optimal decisions in uncertain circumstances flexible adaption of behaviour is required; exploring alternatives when the best choice is unknown, exploiting what is known when that is best. Using a computational model of the basal ganglia, we propose that switches between exploratory and exploitative decisions are mediated by the interaction between tonic dopamine and cortical input to the basal ganglia. We show that a biologically detailed action selection circuit model, endowed with dopamine dependant striatal plasticity, can optimally solve the explore-exploit problem, estimating the true underlying state of a noisy Gaussian diffusion process. ⋯ Model performance was at the level of a Kalman filter which provides an optimal solution for the task. These simulations support the idea that this subcortical neural circuit may have evolved to facilitate decision making in non-stationary reward environments. The model generates several experimental predictions with relevance to abnormal decision making in neuropsychiatric and neurological disease.