Neuroscience
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The endocannabinoid system is a neuromodulatory system which controls the release of multiple neurotransmitters, including glutamate and both, the endocannabinoid and glutamatergic systems, have been implicated in alcohol relapse. Cannabinoid agonists induce an increase in relapse-like drinking whereas glutamate receptor antagonists could prevent it. Here we hypothesize that cannabinoid-induced increases in relapse-like alcohol drinking could be mediated by glutamatergic N-methyl-d-aspartate (NMDA) receptors. ⋯ Interestingly, such changes were blocked after L-701 treatment. Finally, WIN treatment also caused a reduction in NR1 mRNA levels in the amygdala. In conclusion, pharmacological inactivation of the glycine-binding site of NMDA receptors may control cannabinoid-induced relapse-like drinking, which is associated with altered expression of CNR1 and NR1 gene expression as observed after WIN treatment.
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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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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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During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). ⋯ Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS.
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During development, Purkinje axons elongate along precise trajectories and acquire stereotypic branching patterns to innervate targets in the deep nuclei and cerebellar cortex. These processes are accomplished through cell-intrinsic mechanisms, whose operation is regulated by environmental signaling cues. Here, we show that Anosmin-1, the protein defective in the X-linked form of Kallmann syndrome, is one among such cues. ⋯ Comparable results are obtained by administering the protein or the blocking antibodies to organotypic cultures of postnatal (P0) rat cerebellum. In P10 cerebellar slices, Anosmin-1 does not enhance the spontaneous regenerative capabilities of severed Purkinje axons, but promotes the terminal outgrowth of injured neurites into embryonic neocortical explants apposed to the axotomy site. Although Anosmin-1 is unable to change the overall intrinsic growth competence of Purkinje cells, it exerts a powerful stimulatory action on the budding and extension of collateral branches and terminal plexus, contributing to the patterning of Purkinje axons.