Neuroscience
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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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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.
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A major pathological hallmark in several neurodegenerative disorders, like polyglutamine disorders (polyQ), including Machado-Joseph disease (MJD), is the formation of protein aggregates. MJD is caused by a CAG repeat expansion in the ATXN3 gene, resulting in an abnormal protein, which is prone to misfolding and forms cytoplasmic and nuclear aggregates within neurons, ultimately inducing neurodegeneration. Treatment of proteinopathies with drugs that up-regulate autophagy has shown promising results in models of polyQ diseases. ⋯ To further explore this avenue toward therapy, we treated CMVMJD135 transgenic mice with a conjugation of CCI-779 and LiCl, both at concentrations known to induce autophagy and not to be toxic. Surprisingly, this combined treatment proved to be deleterious to both wild-type (wt) and transgenic animals, failing to rescue their neurological symptoms and actually exerting neurotoxic effects. These results highlight the possible dangers of manipulating autophagy in the nervous system and suggest that a better understanding of the potential disruption in the autophagy pathway in MJD is required before successful long-term autophagy modulating therapies can be developed.
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Previous studies often report that early auditory deprivation or congenital deafness contributes to cross-modal reorganization in the auditory-deprived cortex, and this cross-modal reorganization limits clinical benefit from cochlear prosthetics. However, there are inconsistencies among study results on cortical reorganization in those subjects with long-term unilateral sensorineural hearing loss (USNHL). It is also unclear whether there exists a similar cross-modal plasticity of the auditory cortex for acquired monaural deafness and early or congenital deafness. ⋯ Our results indicate that the left primary auditory cortex (non-auditory-deprived cortex) in patients with left USNHL has been reorganized by visual and sensorimotor modalities through cross-modal plasticity. Furthermore, the cross-modal reorganization also alters the directional brain functional networks. The auditory deprivation from the left or right side generates different influences on the human brain.
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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.