Neuroscience
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Ca(2+) binding protein 1 (CaBP1) and caldendrin are alternatively spliced variants of a subfamily of CaBPs with high homology to calmodulin. Although CaBP1 and caldendrin regulate effectors including plasma membrane and intracellular Ca(2+) channels in heterologous expression systems, little is known about their functions in vivo. Therefore, we generated mice deficient in CaBP1/caldendrin expression (C-KO) and analyzed the expression and cellular localization of CaBP1 and caldendrin in the mouse brain. ⋯ By double-label immunofluorescence, CaBP1/caldendrin was localized in principal neurons and parvalbumin-positive interneurons. In the cerebellum, CaBP1/caldendrin antibodies labeled interneurons in the molecular layer and in basket cell terminals surrounding the soma and axon initial segment of Purkinje neurons, but immunolabeling was absent in Purkinje neurons. We conclude that CaBP1/caldendrin is localized both pre- and postsynaptically where it may regulate Ca(2+) signaling and excitability in select groups of excitatory and inhibitory neurons.
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Borna disease virus (BDV) is a neurotropic, non-cytolytic RNA virus which replicates in the cell nucleus targeting mainly hippocampal neurons, but also astroglial and oligodendroglial cells in the brain. BDV is associated with a large spectrum of neuropsychiatric pathologies in animals. Its relationship to human neuropsychiatric illness still remains controversial. ⋯ Five key signaling proteins of this pathway (i.e., p-Raf, p-MEK, p-ERK1/2, p-RSK, and p-MSK) were selected for Western blotting validation. p-ERK1/2 and p-RSK were found to be significantly up-regulated, and p-MSK was found to be significantly down-regulated in BDV Hu-H1-infected OL cells compared to non-infected OL cell. Although BDV Hu-H1 constitutively activated the ERK-RSK pathway, host cell proliferation and nuclear translocation of activated pERK in BDV Hu-H1-infected OL cells were impaired. These findings indicate that BDV Hu-H1 infection of human oligodendroglial cells significantly perturbs host energy metabolism, activates the downstream ERK-RSK complex of the Raf/MEK/ERK signaling cascade, and disturbs host cell proliferation possibly through impaired nuclear translocation of pERK, a finding which warrants further research.
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Tetrodotoxin-sensitive persistent sodium currents, INaP, that activate at subthreshold voltages, have been detected in numerous vertebrate and invertebrate neurons. These currents are believed to be critical for regulating neuronal excitability. However, the molecular mechanism underlying INaP is controversial. ⋯ A1731V is responsible for impaired inactivation and contributes to the portion of INaP at depolarized potentials. Furthermore, A1731V causes enhanced activity of two site-3 toxins which induce persistent currents by inhibiting the outward movement of IVS4, suggesting that A1731V inhibits the outward movement of IVS4. These results provided molecular evidence for the involvement of distinct mechanisms in the generation of INaP: T260 contributes to INaP via enhancement of the window current, whereas V1731 impairs fast inactivation probably by inhibiting the outward movement of IVS4.
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Cerebral activations during olfactory mental imagery are fairly well investigated in healthy participants but little attention has been given to olfactory imagery in patients with olfactory loss. To explore whether olfactory loss leads to deficits in olfactory imagery, neural responses using functional magnetic resonance imaging (fMRI) and self-report measures were investigated in 16 participants with acquired olfactory loss and 19 control participants. Participants imagined both pleasant and unpleasant odors and their visual representations. ⋯ Also, activation in critical areas for olfactory imagery was correlated with the duration of olfactory dysfunction, indicating that the longer the duration of dysfunction, the more the attentional resources were employed. This indicates that participants with olfactory loss have difficulties to perform olfactory imagery in the conventional way. Regular exposure to olfactory information may be necessary to maintain an olfactory imagery capacity.
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Autism Spectrum Disorder (ASD) is often found to co-exist with non-core behavioral manifestations that include difficulties in disengagement of attention to sensory cues. Here we examined whether this behavioral abnormality can be induced in rats prenatally exposed to valproic acid (VPA), a well-established teratogen associated with ASD animal models. We tested rats using an auditory-cued sensorimotor task (ACST) based on the premise that ACST will be more sensitive to developmental changes in temporal association cortex (TeA) of the posterior attention system. ⋯ However, both control and VPA-treated rats performed similarly when tested on novel object recognition (NOR) and novel context mismatch (NOCM) behavioral tasks that are known to be sensitive to normal perirhinal and prefrontal network functioning respectively. Consistent with disrupted posterior rather than frontal networks, we also report that VPA can selectively act on deep-layer TeA cortical neurons by showing that VPA increased dendritic density in isolated deep-layer TeA but not frontal neurons. These results describe a useful approach to examine the role of cue-dependent control of attention systems in rodent models of autism and suggest that disengagement impairments may arise from an inability to modify behavior through the appropriate use of sensory cue associations.