Neuroscience
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In Mammals adult neurogenesis is influenced by environmental conditions, and the glucocorticoid hormones (GC) play a major role in this regulation. In contrast in fish, the study of the effects of cortisol on the regulation of environmental driven adult neurogenesis has produced conflicting results. While in some species elevated cortisol levels impair cell proliferation, in others, it promotes cell proliferation and differentiation. ⋯ Therefore, fish were exposed to a positive (conspecific shoal) or negative (predator) social experience, and the interaction between the valence of the social context and cortisol exposure (acute and chronic) was tested. Our results indicate that adult neurogenesis is modulated by the social environment, with the number of newly generated cells being dependent on the valence of the social information (positive > negative). These effects were independent of cortisol, either for acute or chronic exposure, highlighting the social environment as a key factor in the modulation of cell proliferation in the adult zebrafish brain, and rejecting a role for cortisol in this modulation.
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Understanding the neuro-molecular mechanisms that mediate the quantity of daily physical activity (PA) level is of medical significance, given the tremendous health benefits associated with greater physical activity. Here, we examined the effects of intra-nucleus accumbens (NAc) inhibition of activator protein-1 (AP-1), an important transcriptional factor downstream of cAMP response element binding protein (CREB; a reward-related transcriptional regulator), on voluntary wheel running behavior in wild-type (WT) and low voluntary running (LVR) female rats. Transcriptome analysis of the nucleus accumbens (NAc; a brain region critical for PA reward and motivation) was performed to further determine molecular responses to intra-NAc AP-1 inhibition in these rat lines. ⋯ In contrast to above decreased WT distances, intra-NAc AP-1 inhibition in LVR rats increased nightly running distance in comparison to LVR control rats (p = 0.0008). Further analysis identified gene products that are associated with regulating intracellular Ca2+ homeostasis, calcium ion binding and neuronal excitability. In short, our study aims to gain a comprehensive understanding of transcriptional profile that was due to AP-1 inhibition in NAc, in which it could not only enhance the knowledge regarding molecular regulatory loops within NAc for modulating voluntary running behavior, but also provide further insights into molecular targets for future investigations.
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Fragile XSyndrome (FXS) is a leading known genetic cause of Autism Spectrum Disorders (ASD) and intellectual disability. A consistent and debilitating phenotype of FXS is sensory hypersensitivity that manifests strongly in the auditory domain and may lead to delayed language and high anxiety. The mouse model of FXS, the Fmr1 KO mouse, also shows auditory hypersensitivity, an extreme form of which is seen as audiogenic seizures (AGS). ⋯ Treatment with a combination of NLX-101 and 5-HT1A receptor antagonists prevented the protective effects of NLX-101, indicating that NLX-101 acts selectively through 5-HT1A receptors to reduce audiogenic seizures. NLX-101 (1.8 mg/kg) was still strongly effective in reducing seizures even after repeated administration over 5 days, suggesting an absence of tachyphylaxis to the effects of the compound. Together, these studies point to a promising treatment option targeting post-synaptic 5-HT1A receptors to reduce auditory hypersensitivity in FXS, and potentially across autism spectrum disorders.
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The development and connectivity of retinal ganglion cells (RGCs), the retina's sole output neurons, are patterned by activity-independent transcriptional programs and activity-dependent remodeling. To inventory the molecular correlates of these influences, we applied high-throughput single-cell RNA sequencing (scRNA-seq) to mouse RGCs at six embryonic and postnatal ages. We identified temporally regulated modules of genes that correlate with, and likely regulate, multiple phases of RGC development, ranging from differentiation and axon guidance to synaptic recognition and refinement. ⋯ However, visual deprivation significantly reduced the transcriptomic distinctions among RGC types, implying that activity is required for complete RGC maturation or maintenance. Consistent with this notion, transcriptomic alternations in VD RGCs significantly overlapped with gene modules found in developing RGCs. Our results provide a resource for mechanistic analyses of RGC differentiation and maturation, and for investigating the role of activity in these processes.
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Sensory information in the brain is organized into spatial representations, including retinotopic, somatotopic, and tonotopic maps, as well as ocular dominance columns. The spatial representation of sensory inputs is thought to be a fundamental organizational principle that is important for information processing. Topographic maps are plastic throughout an animal's life, reflecting changes in development and aging of brain circuitry, changes in the periphery and sensory input, and changes in circuitry, for instance in response to experience and learning. Here, we review mechanisms underlying the role of activity in the development, stability and plasticity of topographic maps, focusing on recent work suggesting that the spatial information in the visual field, and the resulting spatiotemporal patterns of activity, provide instructive cues that organize visual projections.