Cerebral cortex
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Stroke induced by middle cerebral artery occlusion in adult rodents induces the formation of new neurons in the damaged striatum, a region that normally does not show neurogenesis. Here we describe recent findings on the regulation of neurogenesis after stroke, in particular regarding the duration of the neurogenic response and the influence of age, as well as the molecular mechanisms influencing migration and survival of the new neurons. We also discuss some crucial issues that need to be addressed in the further exploration of this potential self-repair mechanism after damage to the adult brain.
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Clinical Trial
Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training.
A novel Hebbian stimulation paradigm was employed to examine physiological correlates of motor memory formation in humans. Repetitive pairing of median nerve stimulation with transcranial magnetic stimulation over the contralateral motor cortex (paired associative stimulation, PAS) may decrease human motor cortical excitability at interstimulus intervals of 10 ms (PAS10) or increase excitability at 25 ms (PAS25). The properties of this plasticity have previously been shown to resemble associative timing-dependent long-term depression (LTD) and long-term potentiation (LTP) as established in vitro. ⋯ Application of the PAS protocols after motor training did not prevent the consolidation of motor skills evident as performance gains at later retesting. The results are consistent with a concept of temporary suppression of associative cortical plasticity by neuronal mechanisms involved in motor training. Although it remains an open question exactly which element of motor training was responsible for this effect, our findings may link dynamic properties of LTP formation, as established in animal experiments, with human motor memory formation and possibly dynamic motor learning.
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Clinical Trial
Temporal analysis of cortical mechanisms for pain relief by tactile stimuli in humans.
The mechanisms by which vibrotactile stimuli relieve pain are not well understood, especially in humans. We recorded cortical magnetic responses to paired noxious (intra-epidermal electrical stimulation, IES) and innocuous (transcutaneous electrical stimulation, TS) stimuli applied to the back at a conditioning-test interval (CTI) of -500 to 500 ms. Results showed that IES-induced responses were remarkably attenuated when TS was applied 20-60 ms later and 0-500 ms earlier than IES (CTI = -60 to 500 ms). Since the signals evoked by IES reached the spinal cord (CTI = -60 to -20 ms conditions) and the cortex (-60 and -40 ms condition) earlier than those evoked by TS, the present results indicate that cortical responses to noxious stimuli can be inhibited by innocuous tactile stimuli at the cortical level, with minimal contribution at the spinal level.
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Increasing evidence suggests that in addition to the mesoaccumbens dopamine (DA) system other neurotransmitter and brain systems are also involved in opiate addiction. Recent evidence points to a major involvement of brain norepinephrine (NE) in the behavioral and central effects of opiates and, more specifically, indicates that NE in the prefrontal cortex may have a critical role in rewarding effects of opiates. Moreover, a body of data points to regions within the medial prefrontal cortex (mpFC) acting as final common pathway of drug relapse behavior. ⋯ Selective depletion of medial prefrontal cortical noradrenergic afferents abolished the morphine-induced increase in DA release in the nucleus accumbens. In a second series of experiments, we demonstrated that the same lesion impaired both conditioned place preference (CPP) induced by morphine and reinstatement of an extinguished CPP. The present results indicate that an intact prefrontal cortical NE transmission is necessary for morphine-induced rewarding effects, reinstatement, and mesoaccumbens dopamine release.
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Hippocampal synaptic plasticity is expressed to very different extents in distinct rat strains in vivo. This may correlate with differences in learning ability. We investigated whether the metabotropic glutamate receptor mGluR5 contributes to differences in long-term potentiation (LTP) and learning in freely moving hooded Lister (HL) and Wistar rats. ⋯ Western blot analysis revealed lower expression of mGluR5 in HL compared with Wistar rats. MGluR1 expression was equivalent. These data reveal striking mGluR5-dependent differences in spatial learning in different rat strains, which correlate to synaptic plasticity and mGluR5 expression levels.