Neuroscience
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Axon terminals forming mixed chemical/electrical synapses in the lateral vestibular nucleus of rat were described over 40 years ago. Because gap junctions formed by connexins are the morphological correlate of electrical synapses, and with demonstrations of widespread expression of the gap junction protein connexin36 (Cx36) in neurons, we investigated the distribution and cellular localization of electrical synapses in the adult and developing rodent vestibular nuclear complex, using immunofluorescence detection of Cx36 as a marker for these synapses. In addition, we examined Cx36 localization in relation to that of the nerve terminal marker vesicular glutamate transporter-1 (vglut-1). ⋯ These terminals and their associated Cx36-puncta were substantially depleted after labyrinthectomy. Developmentally, labeling for Cx36 was already present in the vestibular nuclei at postnatal day 5, where it was only partially co-localized with vglut-1, and did not become fully associated with vglut-1-positive terminals until postnatal day 20-25. The results show that vglut-1-positive primary afferent nerve terminals form mixed synapses throughout the vestibular nuclear complex, that the gap junction component of these synapses contains Cx36, that multiple Cx36-containing gap junctions are associated with individual vglut-1 terminals and that the development of these mixed synapses is protracted over several postnatal weeks.
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Reactive astrogliosis, a feature of neuro-inflammation is induced by a number of endogenous mediators including cytokines. Despite interleukin-1 beta (IL-1β) stands out as the major inducer of this process, the underlying mechanism and its role on neuronal viability remain elusive. We investigated in human astrocytoma cells and the rat brain striatum, the role of the nuclear factor-kB (NF-kB) intracellular Ca(2+) concentration ([Ca(2+)]i) calmodulin (CaM) and extracellular regulated mitogen-activated protein kinases (ERK1/2) in IL-1β-induced expression of glial fibrillary acidic protein (GFAP) and neuronal apoptosis associated to a brain trauma. ⋯ The GFAP response was also prevented by antagonizing selectively increase in [Ca(2+)]i, CaM activity or inducible nitric oxide synthase expression with respectively ryanodine plus 2-aminoethoxydiphenyl-borate, N-(6-aminohexyl)-5-chloro-1-naphthalensulfonamide hydrochloride and N-[(3-(aminomethyl)-phenyl]methyl]-ethanimidamide dihydrochloride. Data in vivo supported these findings and showed that GFAP expression induced by IL-1β (50 ng/ml) correlated with attenuated glial scar formation and reduced neuronal apoptosis. Our data identified the NF-kB/Ca(2+)-CaM/ERK signaling pathway as a novel in vivo key regulator of IL-1β-induced astrogliosis which may represent a potential target in neurodegeneration.
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This paper on Rita Levi-Montalcini (1909-2012), who received in 1986 the Nobel Prize in Physiology or Medicine for the discovery of nerve growth factor, focuses on aspects of her advocacy and her commitment to education in which she has been especially active in the last part of her long life. With passionate confidence on the capabilities of the aging brain (together with severe admonition against the pursuit of immortality), she encouraged contributions of senior citizens to the society. Always projected into the future, with enduring faith in the potential of young individuals, in education as a key to development, in the capabilities of women, in the importance of gender equality, Rita established in 2001 the Rita Levi-Montalcini Foundation for the education of African women. Her legacy on engagement for a better 'global village' should not be forgotten by the neuroscience community.
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The role of 5-HT receptors in fluoxetine-induced nociception and antinociception in rats was assessed. Formalin produced a typical pattern of flinching and licking/lifting behaviors. Local peripheral ipsilateral, but not contralateral, pre-treatment with fluoxetine (0.3-3 nmol/paw) increased in a dose-dependent fashion 0.5% formalin-induced nociception. ⋯ In marked contrast, the spinal antinociceptive effect of fluoxetine was prevented by the 5-HT1A (WAY-100635, 0.3-1 nmol/rat), 5-HT1B/1D (GR-127935, 0.3-1 nmol/rat), 5-HT1B (SB-224289, 0.3-1 nmol/rat), 5-HT1D (BRL-15572, 0.3-1 nmol/rat) and 5-HT5A (SB-699551, 1-3 nmol/rat), but not by the 5-HT2A (ketanserin, 3-10 pmol/rat), 5-HT2B (RS-127445, 3-10 pmol/rat), 5-HT2C (RS-102221, 3-10 pmol/rat), 5-HT3 (ondansetron, 3-10 nmol/rat), 5-HT4 (GR-113808, 3-100 fmol/rat), 5-HT6 (SB-258585, 3-10 pmol/rat) nor 5-HT7 (SB-269970, 0.3-1 nmol/rat), receptor antagonists. These results suggest that fluoxetine produces nociception at the periphery by activating peripheral 5-HT2A/2B/2C/3/4/6/7 receptors. In addition, intrathecal fluoxetine produces antinociception by activation of spinal 5-HT1A/1B/1D/5A receptors.
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We previously reported that the novel antidepressant-like effect of tipepidine may be produced at least partly through the activation of mesolimbic dopamine (DA) neurons via inhibiting G protein-coupled inwardly rectifying potassium (GIRK) channels. In this study, we investigated the action of tipepidine on DA D2 receptor-mediated GIRK currents (IDA(GIRK)) and membrane excitability in DA neurons using the voltage clamp and current clamp modes of the patch-clamp techniques, respectively. DA neurons were acutely dissociated from the ventral tegmental area (VTA) in rats and identified by the presence of the hyperpolarization-activated currents. ⋯ Then tipepidine depolarized membrane potential and generated action potentials in the neurons current-clamped. Furthermore, the drug at 40 mg/kg, i.p. increased the number of cells immunopositive both for c-Fos and tyrosine hydroxylase (TH) in the VTA. These results suggest that tipepidine may activate DA neurons in VTA through the inhibition of GIRK channel-activated currents.