The Journal of neuroscience : the official journal of the Society for Neuroscience
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Phasic and tonic light responses provide a fundamental division of visual information that is thought to originate in the inner retina. However, evidence presented here indicates that this duality originates in the outer retina. In response to a steady light stimulus, the temporal responses of On-bipolar cells fell into two groups. ⋯ The antagonist depolarized and blocked the light responses of sustained ganglion cells. In transient ganglion cells, CPPG suppressed the On light response but did not depolarize the cell or block the Off light response. These results suggest that transient and sustained light responses in ganglion cells result from selective bipolar cell input and that these two fundamental visual channels originate at the dendritic terminals of bipolar cells.
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The underlying mechanisms of various types of hereditary dystonia, a common movement disorder, are still unknown. Recent findings in a genetic model of a type of paroxysmal dystonia, the dt(sz) mutant hamster, pointed to striatal dysfunctions. In the present study, immunhistochemical experiments demonstrated a marked decrease in the number and density of parvalbumin-immunoreactive GABAergic interneurons in all striatal subregions of mutant hamsters. ⋯ We conclude that a deficit of striatal GABAergic interneurons leads by disinhibition of striatal GABAergic projection neurons to a reduced activity in the entopeduncular nucleus, i.e., to a decreased basal ganglia output. This finding is in line with the current hypothesis about the pathophysiology of hyperkinesias. The results indicate that striatal interneurons deserve attention in basic and clinical research of those movement disorders.
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Proinflammatory cytokines contribute to the development of inflammatory and neuropathic pain and hyperalgesia in many in vivo models. The rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heat-evoked release of calcitonin gene-related peptide from nociceptors in vitro. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at normal skin temperature of 32 degrees C. ⋯ This suggests a constitutive expression of signaling receptors for TNF and IL-1 beta and the signal transduction molecule gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine signaling observed in the present study was independent of transcriptional pathways because sensitization occurred on short latency in vitro and under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Our results demonstrate that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy.
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A group of neurons with the characteristics of dentate gyrus granule cells was found at the hilar/CA3 border several weeks after pilocarpine- or kainic acid-induced status epilepticus. Intracellular recordings from pilocarpine-treated rats showed that these "granule-like" neurons were similar to normal granule cells (i. e., those in the granule cell layer) in membrane properties, firing behavior, morphology, and their mossy fiber axon. However, in contrast to normal granule cells, they were synchronized with spontaneous, rhythmic bursts of area CA3 pyramidal cells that survived status epilepticus. ⋯ Many BrdU-labeled cells at the hilar/CA3 border also were double-labeled with a neuronal marker (NeuN). Taken together with the recent evidence that granule cells that are born after seizures can migrate into the hilus, the results suggest that some newly born granule cells migrate as far as the CA3 cell layer, where they become integrated abnormally into the CA3 network, yet they retain granule cell intrinsic properties. The results provide insight into the physiological properties of newly born granule cells in the adult brain and suggest that relatively rigid developmental programs set the membrane properties of newly born cells, but substantial plasticity is present to influence their place in pre-existing circuitry.
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Extracellular ATP has been known to activate sensory neurons via the ATP-gated ion channels P2X receptors, indicating that the P2X receptors may play a role in signal transduction of pain from the periphery to the spinal cord in vivo. Here, we found a novel nociceptive response induced by ATP, mechanical allodynia (hypersensitivity to innocuous mechanical stimulus). Injection of alpha,beta-methylene ATP (alpha(beta)meATP), an agonist to P2X receptor, into plantar surface in rats produced the mechanical allodynia along with previously described nocifensive behavior and thermal hyperalgesia. ⋯ ATP has been shown to produce two distinguishable electrophysiological responses (inward currents with rapid and slow desensitization) in dorsal root ganglion (DRG) neurons. In the present electrophysiological experiment, the percentage of DRG neurons that responded to alpha(beta)meATP with slow desensitizing inward current remained constant in capsaicin-treated rats, whereas the percentage that responded with rapid desensitizing current dramatically decreased. Taken together with our previous finding that the alpha(beta)meATP-activated slow desensitizing current in DRG neurons is mediated by heteromeric P2X2/3 (P2X2 and P2X3) receptors, it is hypothesized that activation of heteromeric P2X2/3 receptors in peripheral terminals of capsaicin-insensitive primary afferent fibers leads to the induction of mechanical allodynia.