Neuroscience
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Speech recognition in a multi-talker situation poses high demands on attentional and other central resources. This study examines the relationship between age, cognition and speech recognition in tasks that require selective or divided attention in a multi-talker setting. Two groups of normal-hearing adults (one younger and one older group) were asked to repeat utterances from either one or two concurrent speakers. ⋯ In comparison, speech recognition for tests requiring divided attention could be more strongly determined by neuropsychological probes of fluid intelligence. The findings of this study indicate that - apart from hearing impairment - cognitive aspects account for the typical difficulties of older listeners in a multi-speaker setting. Our results are discussed in the context of evidence showing that frontal lobe functions in terms of working memory and fluid intelligence generally decline with age.
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Dorsal horn neurons send ascending projections to both thalamic nuclei and parabrachial nuclei; these pathways are thought to be critical pathways for central processing of nociceptive information. Afferents from the corneal surface of the eye mediate nociception from this tissue which is susceptible to clinically important pain syndromes. This study examined corneal afferents to the trigeminal dorsal horn and compared inputs to thalamic- and parabrachial-projecting neurons. ⋯ Corneal afferent inputs to both groups of projection neurons were also more abundant in the rostral pole of Vc. Finally, by comparing the frequency of corneal afferent appositions to thalamic- versus parabrachial-projecting neurons, we found that corneal afferents preferentially target parabrachial-projecting neurons in trigeminal dorsal horn. These results suggest that nociceptive pain from the cornea may be primarily mediated by a non-thalamic ascending pathway.
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Parkinson's disease (PD) is a motor disorder that involves death of dopaminergic neurons in the substantia nigra pars compacta. Parkin is an autosomal recessive gene that is mutated in early onset PD. We investigated the role of parkin and autophagic clearance in postmortem nigrostriatal tissues from 22 non-familial sporadic PD patients and 15 control samples. ⋯ Subcellular fractionation showed accumulation of α-Synuclein and tau hyper-phosphorylation (p-Tau) in autophagosomes in gene transfer models, similar to the effects observed in PD brains, but parkin expression led to protein deposition into lysosomes. However, parkin loss of function mutation did not affect autophagic clearance. Taken together, these data suggest that functional parkin regulates autophagosome clearance, while decreased parkin solubility may alter normal autophagy in sporadic PD.
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Recently, we hypothesized that supraspinal structures may have important functions in discriminating between noxious mechanically and heat mediated nociception through distinct functions: facilitation and inhibition. In this study, conducted in conscious rats, we explored the role of different thalamic nuclei: the mediodorsal (MD) nucleus, the central medial (CM) nucleus, the submedius (SM) nucleus, the ventralmedial (VM) nucleus and the ventral posterolateral (VPL) nucleus, in the descending control of secondary and contralateral mechanical hyperalgesia and heat hypoalgesia occurring in intramuscularly hypertonic (HT, 5.8%) saline-induced muscle nociception. ⋯ This descending facilitatory and inhibitory modulation of nociception was strengthened by glutamate, and weakened by GABA, microinjected into the thalamic MD and VM nuclei. It is suggested that (1) thalamic MD nucleus and VM nucleus form two distinct endogenous systems in the control of noxious mechanically and heat evoked responses, and (2) the strengthening of descending inhibition and the weakening of descending facilitation by means of up regulation and down regulation of appropriate receptor expression in the VM and MD nuclei may provide a new strategic policy in treating pathological pain.
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Musculoskeletal pain conditions, particularly those associated with temporomandibular disorders (TMD) affect a large percentage of the population. Identifying mechanisms underlying hyperalgesia could contribute to the development of new treatment strategies for the management of TMD and other muscle pain conditions. In this study, we provide evidence of functional interactions between two ligand-gated channels, P2X₃ and transient receptor potential V1 (TRPV1), in trigeminal sensory neurons, and propose that the interactions serve as an underlying mechanism for the development of mechanical hyperalgesia. ⋯ Significant phosphorylation was observed at 15 min, the time point at which behavioral hyperalgesia was prominent. Previously, activation of either P2X₃ or TRPV1 had been independently implicated in the development of mechanical hyperalgesia. Our data propose P2X₃ and TRPV1 interact in a facilitatory manner, which could contribute to the peripheral sensitization known to underlie masseter hyperalgesia.