Neuroscience
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Intrathecal strychnine (glycine antagonist) or bicuculline (GABA(A) antagonist) yields a touch-evoked agitation that is blocked by N-methyl-D-aspartate receptor antagonism. We examined the effects of intrathecal strychnine and bicuculline on touch-evoked agitation and the spinal release of amino acids. Fifty-two Sprague-Dawley rats were prepared under halothane anesthesia with a lumbar intrathecal catheter and a loop dialysis catheter. ⋯ Intrathecal N-methyl-D-aspartate, strychnine and bicuculline produced similar touch-evoked allodynia. Intrathecal bicuculline and N-methyl-D-aspartate alone evoked a transient spinal release of glutamate and taurine, but not serine, in the 0- 10 min sample, while strychnine did not affect spinal transmitter release at any time. As GABA(A) but not glycine receptor inhibition at equi-allodynic doses increases glutamate release, while the allodynia of both is blocked by N-methyl-D-aspartate receptor antagonism, we hypothesize that GABA(A) sites regulate presynaptic glutamate release, while glycine regulates the excitability of neurons postsynaptic to glutamatergic terminals.
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Neurodegenerative diseases, traumatic brain injury and stroke are likely to result in cognitive dysfunctioning. Animal models are needed in which these deficits and recovery of the affected functions can be investigated. In the present study, the entorhinal area was chosen as the target for lesioning and for assessing the lesion-induced deficits in the Morris water maze. ⋯ The degree of the induced spatial learning impairments and the effects on the rate of acquisition during training, however, differed between experiments. This result suggests that the fundamental biological diversity between shipments of rats can account for variation in the effects of parahippocampal damage on spatial learning even in highly standardized experimental set-ups. Rats lesioned by bilateral injections of ibotenic acid into the entorhinal cortex provide an interesting and reliable model for investigating cognitive dysfunctions in neurodegenerative diseases, stroke or traumatic brain injury.
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This Commentary compares the connections of the dopaminergic system with the striatum in rats and primates with respect to two levels of striatal organization: a tripartite functional (motor, associative and limbic) subdivision and a compartmental (patch/striosome-matrix) subdivision. The topography of other basal ganglia projections to the dopaminergic system with respect to their tripartite functional subdivision is also reviewed. This examination indicates that, in rats and primates, the following observations can be made. (1) The limbic striatum reciprocates its dopaminergic input and in addition innervates most of the dopaminergic neurons projecting to the associative and motor striatum, whereas the motor and associative striatum reciprocate only part of their dopaminergic input. ⋯ Major differences include the following. (1) In rats, neurons projecting to the motor and associative striatum reside in distinct regions, while in primates they are arranged in interdigitating clusters. (2) In rats, the terminal fields of projections arising from the motor and associative striatum are largely segregated, while in primates they are not. (3) In rats, patch- and matrix-projecting dopamine cells are organized in spatially, morphologically, histochemically and hodologically distinct ventral and dorsal tiers, while in primates there is no (bi)division of the dopaminergic system that results in two areas which have all the characteristics of the two tiers in rats. Based on the anatomical data and known dopamine cell physiology, we forward an hypothesis regarding the influence of the basal ganglia on dopamine cell activity which captures at least part of the complex interplay taking place within the substantia nigra between projections arising from the different basal ganglia nuclei. Finally, we incorporate the striatal connections with the dopaminergic system into an open-interconnected scheme of basal ganglia-thalamocortical circuitry.
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Mitogen-activated protein kinases are signal transduction mediators that have been implicated in cell survival and cell death. This study characterized the activation of pathways in the hippocampus during reperfusion after global cerebral ischemia, as well as the influence of a regimen of hypothermia that reduces ischemic cell death in the hippocampus. Circulatory arrest was induced in rats by 8 min of asphyxia. ⋯ In contrast, active stress-activated protein kinase/c-Jun N-terminal kinase immunoreactivity was most intense in the CA3 and dentate gyrus regions. These data demonstrate that both extracellular signal-regulated kinase and stress-activated protein kinase/c-Jun N-terminal kinase pathways are activated during the first 24h of reperfusion after global cerebral ischemia, and that hypothermia increases the activation of extracellular signal-regulated kinase relative to stress-activated protein kinase/c-Jun N-terminal kinase. Thus, an increase in extracellular signal-regulated kinase activation may be associated with improved neuronal survival after ischemic injury.
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Activation of primary afferent C fibers gives rise to spinal release of substance P and glutamate, and these mediators facilitate the cascade of nociceptive processing. We recently showed that intrathecal administration of nociceptin or orphanin FQ (hereafter called nociceptin) induced hyperalgesia to noxious thermal stimuli and allodynia to innocuous tactile stimuli applied to conscious mice. In the present study, we designed experiments to elucidate the pathways and mediators of nociceptin-evoked pain responses. ⋯ In contrast, the nociceptin-evoked allodynia, but not hyperalgesia, disappeared in N-methyl-D-aspartate receptor GluRvarepsilon1 subunit knockout mice. Both nociceptin-evoked hyperalgesia and allodynia were attenuated by morphine in a dose-dependent manner. Taken together, these results demonstrate that capsaicin-sensitive primary afferent fibers are involved not only in thermal hyperalgesia but also in tactile allodynia induced by nociceptin, but in different pathways; the former is mediated by substance P and the latter is mediated by glutamate through the N-methyl-D-aspartate receptor comprising the GluRvarepsilon1 subunit.