The European journal of neuroscience
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Comparative Study
Functional MRI during sleep: BOLD signal decreases and their electrophysiological correlates.
Prominent local decreases in blood oxygenation level (BOLD) can be observed by functional magnetic resonance imaging (fMRI) upon acoustic stimulation during sleep. The goal of this study was to further characterize this BOLD signal decrease with respect to corresponding neurophysiological phenomena using a simultaneous electroencephalography (EEG)/fMRI approach in sleeping human subjects. Healthy volunteers were subjected to acoustic stimulation during non-rapid eye movement (NREM) sleep. ⋯ Our observations provide first evidence that 'negative' BOLD signal changes during human sleep are associated with electrophysiological indicators of altered neuronal activity. Increased number of K-complexes and delta power reflecting hyperpolarization suggests true cortical deactivation upon stimulus presentation. This sleep stage-dependent deactivation might serve to protect the brain from arousing stimuli, particularly during the light phases of sleep shortly after sleep onset.
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Comparative Study
Effects of isolectin B4-conjugated saporin, a targeting cytotoxin, on bladder overactivity induced by bladder irritation.
In order to clarify the functional role of the isolectin B4 (IB4)-binding afferent pathway in the micturition reflex, we investigated the effects on bladder activity of intrathecal application of the IB4-saporin conjugate, a targeting cytotoxin that destroys neurons binding IB4. In rats, IB4-saporin (2.5 micro m) or vehicle was administered through an intrathecal catheter implanted at the level of the L6-S1 spinal cord. Three weeks after IB4-saporin administration, cystometry in conscious animals revealed a reduction in bladder overactive responses induced by intravesical capsaicin or ATP infusion without affecting normal voiding function. ⋯ The percentage of neurons in the L6 DRG intensely labeled with IB4 was also reduced in IB4-saporin-treated rats. These results indicate that intrathecal treatment with the IB4-saporin conjugate at the level of L6-S1 spinal cord, which reduces IB4 afferent nerve terminal staining in lamina II of the L6 spinal cord as well as the number of IB4-binding neurons in L6 DRG, suppressed bladder overactivity induced by bladder irritation without affecting normal micturition. Thus targeting IB4-binding, non-peptidergic afferent pathways sensitive to capsaicin and adenosine 5'-triphosphate may be an effective treatment for overactivity and/or pain responses in the bladder.
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Comparative Study
Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS.
Peripheral inflammation induces central sensitization characterized by the development of allodynia and hyperalgesia to mechanical and thermal stimuli. Recent evidence suggests that activation of glial cells and a subsequent increase in proinflammatory cytokines contribute to the development of behavioral hypersensitivity after nerve injury or peripheral inflammation. In the present study, we examined mRNA and protein expression of glial markers and proinflammatory cytokines at the lumbar spinal cord, brainstem and forebrain following intraplantar administration of complete Freunds adjuvant (CFA) in rats. ⋯ This study demonstrates that CFA-induced peripheral inflammation induces robust glial activation and proinflammatory cytokines both spinally and supraspinally. In addition, similar to nerve injury-induced behavioral hypersensitivity microglial activation preceded astrocytic activation following CFA-induced peripheral inflammation, supporting a role of microglia in the initiation phase and astrocytes in maintaining hypersensitivity. These findings further support a unifying theory that glial activation and enhanced cytokine expression at the CNS have a role in eliciting behavioral hypersensitivity.
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Comparative Study
Input- and subunit-specific AMPA receptor trafficking underlying long-term potentiation at hippocampal CA3 synapses.
Hippocampal CA3 pyramidal neurons receive synaptic inputs from both mossy fibres (MFs) and associational fibres (AFs). Long-term potentiation (LTP) at these synapses differs in its induction sites and N-methyl-D-aspartate receptor (NMDAR) dependence. Most evidence favours the presynaptic and postsynaptic mechanisms for induction of MF LTP and AF LTP, respectively. ⋯ In contrast, no GluR1 AMPAR produced by the gene transfer was constitutively incorporated into AF postsynaptic sites, and only a small amount into MF postsynaptic sites. The synaptic trafficking of GluR1 AMPARs was triggered by the activity of Ca(2+)/calmodulin-dependent kinase II or high-frequency stimulation to induce LTP at AF synapses, but not at MF synapses. These results indicate that MF and AF postsynaptic sites possess distinct properties for AMPAR trafficking in CA3 pyramidal neurons.
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The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) acts as an agonist at group II metabotropic glutamate receptors (mGluRs). NAAG is inactivated by extracellular peptidase activity yielding glutamate and N-acetylaspartate. We recently developed a series of potent NAAG peptidase inhibitors, including ZJ-11, ZJ-17 and ZJ-43. ⋯ These effects of intrathecally or intravenously administered ZJ compounds in both the formalin test and the partial sciatic nerve ligation model were completely antagonized by pretreatment with LY-341495, a highly selective group II mGluR antagonist. Thus, elevation of extracellular NAAG, induced by the inhibition of NAAG peptidase, activates group II mGluRs and produces an analgesic effect in neuropathic and inflammatory and pain models. In contrast, peptidase inhibition did not affect the threshold for withdrawal from a noxious mechanical stimulus or from an acute thermal stimulus in the hotplate test.