The Journal of neuroscience : the official journal of the Society for Neuroscience
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Learning may alter rapidly the output organization of adult motor cortex. It is a long-held hypothesis that modification of synaptic strength along cortical horizontal connections through long-term potentiation (LTP) and long-term depression (LTD) forms one important mechanism for learning-induced cortical plasticity. Strong evidence in favor of this hypothesis was provided for rat primary motor cortex (M1) by showing that motor learning reduced subsequent LTP but increased LTD. ⋯ Repeated fastest possible thumb abduction movements resulted in learning, defined by an increase in maximum peak acceleration of the practiced movements, and prevented subsequent PAS(N20)-induced LTP-like plasticity but enhanced subsequent PAS(N20-5)-induced LTD-like plasticity. The same number of repeated slow thumb abduction movements did not result in learning and had no effects on PAS-induced plasticity. Findings support the view that learning in human M1 occurs through LTP-like mechanisms.
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Phosphorylation of IkappaB through IkappaB kinase (IKK) is the first step in nuclear factor kappaB (NF-kappaB) activation and upregulation of NF-kappaB-responsive genes. Hence, inhibition of IKK activity may be expected to prevent injury-, infection-, or stress-induced upregulation of various proinflammatory genes and may thereby reduce hyperalgesia and inflammation. In the present study, we tested this hypothesis using a specific and potent IKK inhibitor (S1627). ⋯ The drug had no effect on acute inflammatory nociception in the formalin test and did not affect responses to heat and tactile stimuli in naive animals. As hypothesized, S1627 prevented the zymosan-induced nuclear translocation of NF-kappaB in the spinal cord and the upregulation of NF-kappaB-responsive genes including cyclooxygenase-2, tumor necrosis factor-alpha, and IL-1beta. Our data indicate that IKK may prove an interesting novel drug target in the treatment of pathological pain and inflammation.
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We examined the functional organization of the rat trigeminal nuclear complex and its developmental dynamics using a multiple-site optical recording technique. Brainstem preparations were dissected from embryonic day 12 (E12)-E16 rat embryos, and stimulation was applied individually to the three branches of the trigeminal nerve (V1-V3). The action potential activity of presynaptic fibers was detected from E13, and the glutamate-mediated postsynaptic response was significantly observed from E15 on. ⋯ The center of the trigeminal nuclear complex in which the activity of neurons and synaptic function was greatest shifted caudally with development, suggesting that the functional architecture of the trigeminal nuclear complex is not fixed but changes dynamically during embryogenesis. By electron microscopy, we could not observe clear correlations between functional data and morphological information; when we surveyed E16 preparations, we could not identify typical synaptic structures between the 1,1'-dioctyldecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled trigeminal nerve terminals and the neurons in the trigeminal nuclear complex. This implies that postsynaptic function in the trigeminal nuclear complex is generated before the appearance of the morphological structure of conventional synapses.
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Animal and human studies of sleep and learning have demonstrated that training on various tasks increases subsequent rapid eye movement (REM) sleep and phasic pontine-wave (P-wave) activity, followed by improvement in performance on the learned task. It is well documented that REM sleep deprivation after learning trials blocks the expected improvement in performance on subsequent retesting. Our aim was to test whether experimentally induced P-wave generator activation could eliminate the learning impairment produced by post-training REM sleep deprivation. ⋯ In contrast, the rats that received the carbachol microinjection and REM sleep deprivation demonstrated normal learning. These results demonstrate, for the first time, that carbachol-induced activation of the P-wave generator prevents the memory-impairing effects of post-training REM sleep deprivation. This evidence supports our hypothesis that the activation of the P-wave generator during REM sleep deprivation enhances a physiological process of memory, which occurs naturally during post-training REM sleep.
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In Drosophila, light affects circadian behavioral rhythms via at least two distinct mechanisms. One of them relies on the visual phototransduction cascade. The other involves a presumptive photopigment, cryptochrome (cry), expressed in lateral brain neurons that control behavioral rhythms. ⋯ Studies of various visual system mutants and their combination with the cry(b) mutation indicated that the adult DN1s contribute significantly to the light sensitivity of the clock controlling activity rhythms, and that this contribution depends on CRY. Moreover, all CRY-independent light inputs into this central behavioral clock were found to require the visual system. Finally, we show that the photoreceptive DN1 neurons do not behave as autonomous oscillators, because their PER oscillations in constant darkness rapidly damp out in the absence of pigment-dispersing-factor signaling from the ventral lateral neurons.