Neuroscience
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Contrary to the classical view of a pre-determined wiring pattern, there is considerable evidence that cortical representation of body parts is continuously modulated in response to activity, behavior and skill acquisition. Both animal and human studies showed that following injury of the peripheral nervous system such as nerve injury or amputation, the somatosensory cortex that responded to the deafferented body parts become responsive to neighboring body parts. Similarly, there is expansion of the motor representation of the stump area following amputation. ⋯ Changes over a longer time likely involve other additional mechanisms such as long-term potentiation, axonal regeneration and sprouting. While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain. An understanding of the mechanism of plasticity will help to develop treatment programs to improve functional outcome.
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One of us showed previously [Cuajungco and Lees (1998) Brain Res. 799, 188-129] that nitric oxide injected into the cerebrum in vivo causes zinc staining to appear in the somata of neurons and suggested that this staining of somata might be accompanied by a depletion (release) of zinc from axon terminals. In the present study, we confirm earlier results and report that there is a dramatic loss (apparent release) of histologically reactive zinc from the boutons of zinc-containing axons induced by infusion of nitric oxide into the brain in vivo. Rats were anesthetized with halothane and a cannula was inserted into the hippocampus. ⋯ Two hours after infusion, N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining for zinc in the brains revealed that sperminenitric oxide, but not control (spermine only) produced up to 95% depletion of zinc staining from the zinc-containing boutons. TSQ-positive neurons were also conspicuous throughout injection sites, in both the cerebral cortex and in the cerebellar cortex, where the Purkinje neurons were especially vivid, despite the scarcity of zinc-containing axonal boutons. It is suggested that the TSQ-stainable zinc in somata might represent intracellular stores mobilized from within or permeating extracellular stores.
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Adult rat sensory neurones were maintained in short-term tissue culture and their response to histamine was studied by monitoring changes in intracellular [Ca(2+)] with Fura-2. The proportion of histamine-sensitive neurones increased as the concentration increased from 10 microM to 10 mM. The fraction of responding cells did not change significantly over the first week in culture. ⋯ A combination of U73122 and calcium-free medium abolished all responses to histamine. These data suggest that in addition to activating phospholipase C, high concentrations of histamine gate an influx of calcium that is independent of store depletion. The implications of these results for the transduction of pruritic stimuli is discussed.
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Opioid antinociception appears to be mediated at least in part by a pathway that projects from the periaqueductal gray (PAG) to the rostral ventromedial medulla (RVM), but the relationship between opioid receptors and PAG-RVM projection neurons is unclear. Previous electrophysiological studies have suggested that opioids act directly on some PAG neurons projecting to the RVM. However, immunoreactivity for neither the cloned mu-opioid receptor (MOR1) nor the cloned delta-opioid receptor (DOR1) has been observed in PAG cells retrogradely labeled from the RVM. ⋯ However, no significant difference was observed in the proportions of retrogradely labeled neurons labeled for DOR1 mRNA in the ventrolateral subregion compared to the dorsomedial subregion. We conclude that opioids are likely to exert direct effects on PAG-RVM projection neurons through both delta- and mu-opioid receptors. In addition, direct effects on PAG-RVM projection neurons from activation of MOR1 appear more likely to be exerted in the ventrolateral PAG than in the dorsomedial PAG.
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In the present study we have investigated the possible role of gap junctions in the induction and manifestation of 4-aminopyridine-induced acute seizure activity both at the primary focus and at the mirror focus in anaesthetized rats by combining electrophysiological, pharmacological and molecular biological techniques. In the course of the intracellular recordings, unusual firing patterns that are assumed to be mediated by electrical coupling and appearing either randomly or in close time-locked manner with the ictal discharges were observed. In another series of experiments, a significant decrease in the intensity of seizure activity of the already active epileptic foci was detected when electrical synaptic transmission was blocked by carbenoxolone either at the primary focus or at the mirror focus. ⋯ Both, connexin-32 and connexin-43 mRNA levels were significantly elevated at the primary focus as well as at the mirror focus, after 60 min of repeated ictal discharges. We conclude that gap junction communication probably became a part of the neuronal synchronization both in the primary and in the secondarily-induced acute epileptiform activity in the neocortex in vivo. These results, together with earlier observations, indicate a direction for the development of new drugs targeting gap junctions for therapeutic intervention.