The Journal of neuroscience : the official journal of the Society for Neuroscience
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Practice can improve performance on visual search tasks; the neural mechanisms underlying such improvements, however, are not clear. Response time typically shortens with practice, but which components of the stimulus-response processing chain facilitate this behavioral change? Improved search performance could result from enhancements in various cognitive processing stages, including (1) sensory processing, (2) attentional allocation, (3) target discrimination, (4) motor-response preparation, and/or (5) response execution. We measured event-related potentials (ERPs) as human participants completed a five-day visual-search protocol in which they reported the orientation of a color popout target within an array of ellipses. ⋯ Third, the amplitude of the sustained posterior contralateral negativity component (SPCN, 300-400 ms) decreased, indicating facilitated target discrimination. Finally, faster motor-response preparation and execution were observed after practice, as indicated by latency changes in both the stimulus-locked and response-locked lateralized readiness potentials (LRPs). These electrophysiological results delineate the functional plasticity in key mechanisms underlying visual search with high temporal resolution and illustrate how practice influences various cognitive and neural processing stages leading to enhanced behavioral performance.
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EphB1, expressed in Müller cells, and ephrinB2, expressed in both Müller cells and retinal ganglion cells (RGCs), constitute an EphB/ephrinB reverse signaling in RGCs. Whether and how this reverse signaling is involved in RGC apoptosis in a rat chronic ocular hypertension (COH) model was investigated. In the COH model, both EphB1 and ephrinB2 were significantly increased and the reverse signaling was activated, which was accompanied by increased protein levels of phosphorylated (p) src, GluA2, and p-GluA2. ⋯ Patch-clamp experiments further showed that the current-voltage relationship of AMPA receptor-mediated EPSCs of RGCs exhibited stronger inward rectification in EphB2-Fc-injected rats. Furthermore, preinjection of PP2 or N-[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]-1-naphthaleneacetamide trihydrochloride) (Naspm), a Ca(2+)-permeable GluA2-lacking AMPA receptor inhibitor, remarkably inhibited RGC apoptosis in either EphB2-Fc-injected or COH rats. Together, elevated GluA2 trafficking induced by activated EphB2/ephrinB2 reverse signaling likely contributes to RGC apoptosis in COH rats.
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Within the hippocampus, different kinds of spatial experience determine the direction of change of synaptic weights. Synaptic plasticity resulting from such experience may enable memory encoding. The CA3 region is very striking in this regard: due to the distinct molecular properties of the mossy fiber (MF) and associational-commissural (AC) synapses, it is believed that they enable working memory and pattern completion. ⋯ MGlu5 activation had no effect on AC responses but potentiated MF synapses. These data suggest that mGlu5 serves as a switch that alters signal-to-noise ratios during information encoding in the CA3 region. This mechanism supports highly tuned and differentiated information storage in CA3 synapses.
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As one of the most effective and frequently used chemotherapeutic agents, paclitaxel produces peripheral neuropathy (paclitaxel-induced peripheral neuropathy or PIPN) that negatively affects chemotherapy and persists after cancer therapy. The mechanisms underlying this dose-limiting side effect remain to be fully elucidated. This study aimed to investigate the role of nociceptor protein kinase C (PKC) isoforms in PIPN. ⋯ Surprisingly, spinal inhibition of PKCβII and PKCδ, but not PKCϵ, blocked the spontaneous pain induced by paclitaxel. These data suggest that a subset of nociceptor PKC isoforms differentially contribute to spontaneous and evoked pain in PIPN, although it is not clear whether PKCϵ in other regions regulates spontaneous pain in PIPN. The findings can potentially offer new selective targets for pharmacological intervention of PIPN.
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Adult neural stem cells reside in specialized niches. In the ventricular-subventricular zone (V-SVZ), quiescent neural stem cells (qNSCs) become activated (aNSCs), and generate transit amplifying cells (TACs), which give rise to neuroblasts that migrate to the olfactory bulb. The vasculature is an important component of the adult neural stem cell niche, but whether vascular cells in neurogenic areas are intrinsically different from those elsewhere in the brain is unknown. ⋯ Unexpectedly, diffusible cortical signals had the most potent effects on V-SVZ proliferation and neurogenesis, highlighting the intrinsic capacity of non-neurogenic vasculature to support stem cell behavior. Finally, we identify PlGF-2 as an endothelial-derived mitogen that promotes V-SVZ cell proliferation. This purification strategy provides a platform to define the functional and molecular contribution of vascular cells to stem cell niches and other brain regions under different physiological and pathological states.