Neuroscience
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Harnessing the regenerative capabilities of endogenous precursor cells in the spinal cord may be a useful tool for clinical treatments aimed at replacing cells lost as a consequence of disease or trauma. To better understand the proliferative properties and differentiation potential of the adult spinal cord after injury, we used a mouse model of compression spinal cord injury (SCI). After injury, adult mice were administered BrdU to label mitotic cells and sacrificed at different time-points for immunohistochemical analysis. ⋯ At early time-points after injury, BrdU(+) cells mainly expressed microglial/macrophage and astrocytic markers, while at these same time-points in the control spinal cord the mitotic cells predominately expressed oligodendrocyte and oligodendrocyte progenitor cell markers. The profile of proliferation and cell fate marker expression indicates that after moderate compression, the spinal cord has the capacity to generate a variety of glial cells but not neurons, and that this pattern is space and time specific. Future studies should focus on ways to control proliferation and cell fate after injury to aid the development of cell replacement treatments for SCI.
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We have previously shown that anti-hyperalgesic effects of cannabinoid agonists under inflammatory condition are much greater in male than female, and that inflammatory cytokines upregulate cannabinoid receptor type 1 (CB1) expression in male, but not female, trigeminal ganglia (TG) in a testosterone-dependent manner. In this study, we investigated the mechanisms underlying the testosterone-mediated regulation of peripheral CB1 expression. We hypothesized that testosterone upregulates CB1 through transcriptional modulation by androgen receptor (AR). ⋯ Furthermore, luciferase reporter assay revealed that AR activated the CB1 gene in response to testosterone or dihydrotestosterone treatment. These experiments provided compelling evidence that testosterone regulates CB1 gene transcription in TG through AR following cytokine stimulation. These results should provide mechanistic bases for understanding cytokine-hormone-neuron interactions in peripheral cannabinoid systems, and have important clinical implications for pain patients in whom testosterone level is naturally low, gradually declining or pharmacologically compromised.
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Extracellular local field potentials (LFPs) and multiunit activity (MUA) reflect the spatially integrated activity of multiple neurons in a given cortical structure. In the cat and primate visual cortices, these signals exhibit selectivity for visual stimulus features, such as orientation, direction of motion or spatial frequency. In the mouse visual cortex, a model which has been increasingly used in visual neuroscience, the visual stimulus selectivity of population signals has not been examined in detail. ⋯ All four population signals exhibited similar spatial frequency preferences (∼0.1 cycles per degree) and temporal frequency preferences (∼1 cycle per second). However, for all population signals, spatial and frequency tunings were broad and orientation and direction of motion preferences were absent. The characterization of the visual stimulus selectivity of LFPs and MUA in the mouse visual cortex should provide information regarding their usability in characterizing stimulus properties and disclose possible limitations.
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In this review we discuss recent advances in the understanding of the development of forebrain projections attending to their origin, fate determination, and axon guidance. Major forebrain connections include callosal, corticospinal, corticothalamic and thalamocortical projections. Although distinct transcriptional programs specify these subpopulations of projecting neurons, the mechanisms involved in their axonal development are similar. ⋯ Moreover, some of these connections interact with each other showing that the development of these axonal tracts is a well-orchestrated event. Finally, we will recapitulate recent discoveries that challenge the field of neural wiring that show that these forebrain connections can be changed once formed. The field of reprogramming has arrived to postmitotic cortical neurons and has showed us that forebrain connectivity is not immutable and might be changed by manipulations in the transcriptional program of matured cells.