Neuroscience
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Gene expression is a necessary step for memory re-stabilization after retrieval, a process known as reconsolidation. Histone acetylation is a fundamental mechanism involved in epigenetic regulation of gene expression and has been implicated in memory consolidation. However, few studies are available in reconsolidation, all of them in vertebrate models. ⋯ Accordingly, we found the first evidence that the administration of a histone acetyl transferase inhibitor during memory reconsolidation impairs long-term memory re-stabilization. Finally, we found that strong training memory, at variance with the standard training memory, was resistant to extinction, indicating that such strong training induced in fact a stronger memory. In conclusion, the results presented here support that the participation of histone acetylation during reconsolidation is an evolutionary conserved feature and constitutes a specific molecular characteristic of strong memories.
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We have assessed the mechanism underlying glial cell-derived neurotrophic factor (GDNF)-induced mechanical hyperalgesia in the gastrocnemius muscle, using patch clamp electrophysiology, in vivo electrophysiology and behavioral studies. Cultured isolectin B4-positive (IB4+) dorsal root ganglion neurons that innervated this muscle were held under current clamp; the majority developed an increase in action potential duration (a factor of increase of 2.29±0.24, compared to 1.13±0.17 in control, P<0.01) in response to GDNF (200 ng/ml) by 15 min after application. They also demonstrated a depolarization of resting membrane potential, but without significant changes in rheobase, action potential peak, or after-hyperpolarization. ⋯ This was observed in the absence of changes in the mechanical threshold. Finally, injection of iberiotoxin into the gastrocnemius muscle produced dose-dependent mechanical hyperalgesia. These data support the suggestion that GDNF induces nociceptor sensitization and mechanical hyperalgesia, at least in part, by inhibiting BK current in IB4+ nociceptors.
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The medial amygdaloid nucleus (MeA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the MeA of unanesthetized rats caused pressor and bradycardiac responses, which were mediated by acute vasopressin release into the systemic circulation. ⋯ Pressor and bradycardiac responses to the microinjection of NA (27 nmol/100 nL) into the MeA were blocked by pretreatment of either the PVN or the SON with cobalt chloride (CoCl(2), 1 mM/100 nL), thus indicating that both hypothalamic nuclei mediate the cardiovascular responses evoked by microinjection of NA into the MeA. Our results suggest that the pressor and bradycardiac response caused by the microinjection of NA into the MeA is mediated by magnocellular neurons in both the PVN and SON.
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The generation of the most abundant neurons of the cerebellum, the granule cells, relies on a balance between clonal expansion and apoptosis during the first 10 days after birth in the external germinal layer (EGL). The amino acid glutamate controls such critical phases of cell development in other systems through specific receptors such as metabotropic glutamate receptor 5 (mGlu(5)R). However, the function of mGlu(5)Rs on the proliferation and survival of granule cell precursors (GCPs) remains elusive. ⋯ Furthermore, similar treatments led to a significant 70% decrease in the number of apoptotic GCPs in the EGL as determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. In contrast, in vivo treatment with the mGlu(5)R agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) resulted in a ∼60% increase in the number of TUNEL-labeled GCPs compared to control. These findings identify a unique role for glutamate acting at mGlu(5)Rs as a functional switch regulating GCP survival in the EGL, thus controlling the total number of cerebellar granule cells produced.
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Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. It has been shown in rats that the acute administration of recombinant human erythropoietin (rhEPO) following a contusive SCI improves the recovery of hindlimb motor function, as measured with the locomotor BBB (Basso, Beattie, Bresnahan) scale. This scale evaluates overall locomotor activity, without testing whether the rhEPO-induced motor recovery is due to a parallel recovery of sensory and/or motor pathways. ⋯ In rhEPO-treated animals results show a better general improvement both in sensory and motor transmission through spared spinal pathways, supposedly via the reticulo-spinal system, with respect to saline controls. This improvement is most prominent at relatively early times. Overall these features show a parallel time course to the changes observed in BBB score, suggesting that EPO-mediated spared spinal cord pathways might contribute to the improvement in transmission which, in turn, might be responsible for the recovery of locomotor function.