Neuroscience
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Varicella zoster virus (VZV) is responsible for chronic pain. VZV injection has similarities to herpes zoster (HZ) "shingles" pain in humans. In this study orofacial pain was induced by injecting male rats with the human VZV. ⋯ Attenuating Nrxn3 expression also increases VZV associated orofacial pain. Activating GABAergic neurons within the central amygdala with opsins increase GABA release in the parabrachial and reduced the pain response after Nrxn3 shRNA treatment. These results are consistent with the idea that Nrxn3 within the central amygdala controls VZV associated pain by regulating GABA release in the lateral parabrachial that then controls the activity of ascending pain neurons.
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Subtypes of microglia/macrophage regulate the inflammation in the opposite direction during ischemic stroke. JAK2/STAT3 signaling pathway participates in the development of stroke-related inflammation via ischemic stimulation. However, the relationship between JAK2/STAT3 pathway and microglia/macrophage phenotype transformation is unclear. ⋯ Collectively, these results reveal that JAK2/STAT3 signaling pathway regulates the microglia/macrophage polarization (skewing toward the M2 polarization) during the CIRI, thus alleviating brain damage. Therefore, approaches targeting JAK2/STAT3 activation are promising therapies for ischemic stroke.
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Disturbance in synaptic excitatory and inhibitory (E/I) transmission in the prefrontal cortex is considered a critical factor for cognitive dysfunction, a core symptom in schizophrenia. However, the cortical network pathophysiology induced by E/I imbalance is not well characterized, and an effective therapeutic strategy is lacking. In this study, we simulated imbalanced cortical network by using mice with parvalbumin neuron (PV) specific knockout of GluA1 (AMPA receptor subunit 1) (Gria1-PV KO) as an experimental model. ⋯ Our results suggest that PV-specific deletion of GluA1 might be an experimental approach for back translating the E/I imbalance observed in schizophrenic patients. Our work offers a systematic workflow to understand the effect of GlyT1 inhibition in restoring cortical network activity from single cells to local brain circuitry. This study highlights that selectively boosting NMDA receptor-mediated excitatory drive to enhance the network inhibitory transmission from interneurons to pyramidal neurons (PYs) is a potential therapeutic strategy for restoring E/I imbalance-associated cognitive-related abnormality.
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Interlimb coordination deteriorates as a result of aging. Due to its ubiquity in daily life, a greater understanding of the underlying neurophysiological changes is required. Here, we combined electroencephalography time-frequency spectral power and functional connectivity analyses to provide a comprehensive overview of the neural dynamics underlying the age-related deterioration of interlimb coordination involving all four limbs. ⋯ Overall, spectral results suggest that enhanced beta desynchronization in older adults reflects a successful compensatory mechanism to cope with increased difficulty during complex interlimb coordination. Functional connectivity results suggest that theta and alpha band connectivity are prone to respectively task- and age-related modulations. Future work could target these spectral and functional connectivity dynamics through noninvasive brain stimulation to potentially improve interlimb coordination in older adults.