Neuroscience
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Memory consolidation and reconsolidation in an invertebrate model: the role of the GABAergic system.
Consolidation theory assumes that memories are labile during a limited time window after acquisition, but as time passes, memories become stable and resistant to amnesic agents. However, the vision of immutable memories after consolidation has been challenged. Thus, after the presentation of a reminder, the reactivated old memories become labile and again susceptible to amnesic treatments. ⋯ The ubiquity of the neurotransmitter and its receptors in the animal taxa allows us to use the classic agonist-and-antagonist administration procedure in this invertebrate. Thus, all the results reported in this paper can be judged as a result of the modulation exerted by the functional state of the GABAergic system in the CNS. To conclude, the results obtained in this report with an invertebrate model represent additional evidences supporting the view that some molecular mechanisms subserving different memory phases could be the basic tools employed by phylogenetically disparate animals.
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Among the GABAergic neocortical interneurons, parvalbumin-containing fast-spiking (FS) basket cells are essential mediators of feed-forward inhibition, network synchrony and oscillations, and timing of the critical period for sensory plasticity. The FS phenotype matures after birth. It depends on the expression of the voltage-gated potassium channels Kv3.1b/3.2 which mediate the fast membrane repolarization necessary for firing fast action potentials at high frequencies. ⋯ Recovery from dark rearing normalized Kv3.2 expression. This showed that visual experience influences the Kv3 expression. The results suggest that an altered expression of Kv3 channels affects the functional properties of FS neurons, and may contribute to the deficits in inhibition observed in the sensory-deprived cortex.
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Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in brain development and the etiology of adult cerebral injuries. In this study, we determined the MMP-2 and 9 responses following hypoxic ischemia (HI) injury in the developing brain. First, we characterized the developmental changes of MMP activity in the rat brain from embryonic day 18 (E18) to postnatal day 120 (P120). ⋯ Immunohistochemistry indicated that MMP-9 protein expression was localized predominantly to neurons and peri-vascular astrocytes in the affected regions at early time points, whereas MMP-2 was present on reactive astrocytes surrounding the infarct at later time points. Together, these results indicate that MMP-2 may be primarily associated with the development and differentiation of cortical plate neurons and wound recovery processes. Conversely, MMP-9 appeared to be associated with more acute processes during the period of lesion development.
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Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. ⋯ Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.
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Penetrating limb injuries are common and usually heal without long-lasting effects, even when nerves are cut. However, rare nerve-injury patients develop prolonged and disabling chronic pain (neuralgia). When pain severity is disproportionate to severity of the inciting injury, physicians and insurers may suspect exaggeration and limit care or benefits, although the nature of the relationship between lesion-size and the development and persistence of neuralgia remains largely unknown. ⋯ Numbers of GFAP-immunoreactive astrocytes increased independently of lesion size and pain status. Small nerve injuries can thus have magnified and disproportionate effects on dorsal-horn neurons and glia, perhaps providing a biological correlate for the disproportionate pain of post-traumatic neuralgias (including complex regional pain syndrome-I) that follow seemingly minor nerve injuries. However, the presence of similar dorsal-horn changes in rats without pain behaviors suggests that not all transcellular responses to axotomy are pain-specific.