Neuroscience
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The cholinergic neurons which originate in the mesopontine tegmentum and innervate the midbrain ventral tegmental area have been proposed to play a key role in intracranial self-stimulation reward. This mesopontine area also contains GABA neurons. Detailed information is still lacking, however, about the relationship of cholinergic and GABAergic neurons in this region to self-stimulation reward. ⋯ One hour of self-stimulation significantly increased acetylcholine efflux from this terminal area. These results indicate that intracranial self-stimulation of the medial forebrain bundle may increase acetylcholine release without affecting expression of Fos in cholinergic neurons, while the same stimulation may induce Fos expression in GABAergic neurons of the mesopontine tegmentum. GABAergic as well as cholinergic neurons in this area appear to be activated by self-stimulation reward in the medial forebrain bundle.
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We previously reported that Parkinson's disease patients could point with their eyes closed as accurately as normal subjects to targets in three-dimensional space that were initially presented with full vision. We have now further restricted visual information in order to more closely examine the individual and combined influences of visual information, proprioceptive feedback, and spatial working memory on the accuracy of Parkinson's disease patients. All trials were performed in the dark. ⋯ The current study supports an important role for the basal ganglia in the integration of proprioceptive signals with concurrent or remembered visual information that is needed to guide movements. This role can explain much of the patients' dependence on visual information for accuracy in targeted movements. It also underlines what may be an essential contribution of the basal ganglia to movement, the integration of afferent information that is initially processed through multiple, discrete modality-specific pathways, but which must be combined into a unified and continuously updated spatial model for effective, accurate movement.
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Detailed electrophysiological characterisation of spinal opioid receptors in the mouse has been limited due to various technical difficulties. In this study, extracellular single unit recordings were made from dorsal horn neurones in a perfused spinal cord with attached trunk-hindquarter to investigate the role of delta-opioid receptor in mediating nociceptive and non-nociceptive transmission in mouse. Noxious electrical shock, pinch and heat stimuli evoked a mean response of 20.8+/-2.5 (n=10, P<0.005), 30.1+/-5.4 (n=58, P<0.005) and 40.9+/-6.3 (n=29, P<0.005) spikes per stimulus respectively. ⋯ In contrast, the responses of non-nociceptive dorsal horn neurones were not inhibited by SNC 80 at a dose of up to 10 microM (n=5). These data demonstrate that delta-opioid receptor modulate nociceptive, but not non-nociceptive, transmission in spinal dorsal horn neurones of the adult mouse. The potentiation of neuronal activity by HS 378 may reflect an autoregulatory role of the endogenous delta-opioid in nociceptive transmission in mouse.
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Comparative Study
Increased conduction velocity of nociceptive primary afferent neurons during unilateral hindlimb inflammation in the anaesthetised guinea-pig.
Decreases in durations of action potentials (C- and Adelta-fibre units) and afterhyperpolarisations (A-fibre units) occur in somata of nociceptive dorsal root ganglion neurons during hindlimb inflammation induced in young guinea-pigs by intradermal injections of Complete Freund's Adjuvant into the ipsilateral leg and foot. Here we present evidence that the single-point conduction velocity (i.e. estimated over a single conduction distance) of these nociceptive neurons is increased during this type of inflammation. The single-point conduction velocities in anaesthetised untreated guinea-pigs (control) were compared with those two and four days after Complete Freund's Adjuvant treatment in two types of experiment. ⋯ The conduction velocity increases may be due to altered expression or activation/inactivation of certain ion channel types, such as Na(+) channels. The present experiments demonstrate that hindlimb inflammation caused a significant increase in conduction velocity of nociceptive but not of low-threshold mechanoreceptive primary afferent neurons during inflammation, as well as a significant decrease in the mean electrical threshold for eliciting the C and Adelta components of compound action potentials of both dorsal root and sural nerves. These changes, together with the previously described changes in the action potential shape of nociceptive neurons during inflammation, probably reflect alterations in membrane function that contribute to inflammatory hyperalgesia.
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Apoptosis or programmed cell death has been reported after CNS trauma. However, the significance of this mechanism in the pathophysiology of spinal cord injury, in particular at the cervical level, requires further investigation. In the present study, we used the extradural clip compression model in the rat to examine the cellular distribution of apoptosis following cervical spinal cord injury, the relationship between glial apoptosis and post-traumatic axonal degeneration and the possible role of apo[apoptosis]-1, CD95 (FAS) and p75 in initiating post-traumatic glial apoptosis. ⋯ The downstream caspases 3 and 8, which are linked to FAS and p75, demonstrated activation at times of maximal apoptosis, while FLIP-L an inhibitor of caspase 8, decreased at times of maximal apoptosis. We conclude that axonal degeneration after traumatic spinal cord injury is associated with glial, in particular oligodendroglial, apoptosis. Activation of the FAS and p75 death receptor pathways may be involved in initiating this process.