Neuroscience
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In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. ⋯ Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain.
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Delta opioid (DOP) receptors participate to the control of chronic pain and emotional responses. Recent data also identified their implication in spatial memory and drug-context associations pointing to a critical role of hippocampal delta receptors. To better appreciate the impact of repeated drug exposure on their modulatory activity, we used fluorescent knock-in mice that express a functional delta receptor fused at its carboxy-terminus with the green fluorescent protein in place of the native receptor. ⋯ In addition, we observed increased DOP receptor expression at the cell surface compared to saline-treated animals. In the hippocampus, chronic morphine administration thus induces DOP receptor cellular redistribution and durably decreases delta receptor-expressing cell density. Such modifications are likely to alter hippocampal physiology, and to contribute to long-term cognitive deficits.
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Task switching is our ability to abandon an old, irrelevant task in order to perform a new, more relevant one. Data from neuropsychology and neuroimaging studies indicate hemispheric asymmetries in task switching, however the neural mechanisms subtending switching, and in particular protocols to improve switching abilities are yet to be established. The present study aimed to assess hemispheric asymmetry and practice effects in task switching by using transcranial direct current stimulation (tDCS). ⋯ The task was repeated three times in three separate sessions in order to test practice effects with and without stimulation. Results show that increased hemispheric asymmetry in dorsolateral prefrontal areas improved switching performance as measured by a better practice effect, compared to sham condition. Our results support the hypothesis of dynamic hemispheric asymmetry in task switching and reinforce the notion of utilizing brain stimulation with traditional training methods in order to enhance cognitive abilities.
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Beta-arrestins (β-arrs) are initially known as negative regulators of G protein-coupled receptors (GPCRs). Recently, there is increasing evidence suggesting that β-arrs also serve as scaffolds and adapters that mediate distinct intracellular signal transduction initiated by GPCR activation. In the previous study, we have shown that metabotropic glutamate receptor 7 (mGluR7) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling may be involved in the developmental sevoflurane neurotoxicity. ⋯ For the behavior study, treatment with LAP4 or AMN082 significantly improved the emotional and spatial learning and memory disorders induced by postnatal sevoflurane exposure. These results suggested that β-arr1 and 2 may differently modulate mGluR7 signaling in developmental sevoflurane neurotoxicity. This study also reveals a β-arr-biased agonism at GPCRs (e.g. mGluR7).
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The locus coeruleus (LC) has been suggested as a CO2 chemoreceptor site in mammals. Most of the studies involving the role of the LC in hypercapnic ventilatory responses have been performed in males. Since ovarian steroids modulate the activity of LC neurons and females have a different respiratory response to CO2 than males, we evaluated the activity of LC noradrenergic neurons during normocapnia and hypercapnia in female and male rats with distinct sex hormone levels. ⋯ In the OVX+E2 group, there was attenuation in the c-Fos expression during normocapnia compared with OVX rats, but CO2 responsiveness was not altered. Moreover, in ORX rats, neither T nor E2 treatments changed c-Fos expression in LC noradrenergic neurons. Thus, in female rats, E2 reduces activation of LC noradrenergic neurons, whereas in males, sex hormones do not influence the LC activity.