Neuroscience
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Cortical involvement in postural control is well recognized, however the role of non-visual afferents remains unclear. Parietal cortical areas are strongly implicated in vestibulo-spatial functions, but topographical localization during balance tasks remains limited. Here, we use electroencephalography (EEG) during continuous balance tasks of increasing difficulty at single electrode positions. ⋯ Our results demonstrate the functional importance of bilateral central and parietal cortices in continuous balance control. The hemispheric asymmetry observed implies that the non-dominant hemisphere is involved with online monitoring of postural control. Although the posterior parietal asymmetry found may relate to vestibular, somatosensory or multisensory feedback processing, we argue that the finding relates to active balance control rather than simple sensory-intake or reflex circuit activation.
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The Weak Central Coherence account of autism spectrum disorders posits that individuals with ASD utilize a detail-oriented information processing bias. While this local bias is helpful in visual search tasks, ASD individuals falter in social cognition tasks where coherence is advantageous. The present study examined the neural correlates of Weak Central Coherence in ASD during visual and social processing. ⋯ The TD group showed significantly increased areas of activity over the ASD group in the Shape task in regions associated with executive control, such as the medial prefrontal cortex and middle frontal gyrus, suggesting increased interference from the global/social information. During the Emotion condition, the ASD group showed decreased connectivity between frontal and posterior regions and between body perception and motor networks, suggesting a possible difference in mirroring. The findings suggest that social cognitive factors, not visual processing biases, underlie the observed behavioral differences.
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Cognitive impairment (CI), a debilitating and pervasive feature of multiple sclerosis (MS), is correlated with hippocampal atrophy. Findings from postmortem MS hippocampi indicate that expression of genes involved in both excitatory and inhibitory neurotransmission are altered in MS, and although deficits in excitatory neurotransmission have been reported in the MS model experimental autoimmune encephalomyelitis (EAE), the functional consequence of altered inhibitory neurotransmission remains poorly understood. In this study, we used electrophysiological and biochemical techniques to examine inhibitory neurotransmission in the CA1 region of the hippocampus in EAE. ⋯ Although plasma membrane expression of the GABA transporter GAT-3 was decreased in the EAE hippocampus, an increased surface expression of α5 subunit-containing GABAA receptors appears to be primarily responsible for the increase in tonic inhibition during EAE. Enhanced tonic inhibition during EAE was associated with decreased CA1 pyramidal cell excitability and inhibition of α5 subunit-containing GABAA receptors with the negative allosteric modulator L-655,708 enhanced pyramidal cell excitability in EAE mice. Together, our results suggest that altered GABAergic neurotransmission may underlie deficits in hippocampus-dependent cognitive function in EAE and MS.
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Stimulation of the mu-opioid receptor (MOR) on nociceptors with fentanyl can produce hyperalgesia (opioid-induced hyperalgesia, OIH) and hyperalgesic priming, a model of transition to chronic pain. We investigated if local and systemic administration of biased MOR agonists (PZM21 and TRV130 [oliceridine]), which preferentially activate G-protein over β-arrestin translocation, and have been reported to minimize some opioid side effects, also produces OIH and priming. Injected intradermally (100 ng), both biased agonists induced mechanical hyperalgesia and, when injected at the same site, 5 days later, prostaglandin E2 (PGE2) produced prolonged hyperalgesia (priming). ⋯ Hyperalgesia, analgesia and priming induced by systemic administration of PZM21 were also prevented by MOR AS-ODN. And, priming induced by systemic PZM21 was also not reversed by intradermal cordycepin or the combination of Src and MAPK inhibitors. Thus, maintenance of priming induced by biased MOR agonists, in the peripheral terminal of nociceptors, has a novel mechanism.