Neuroscience
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TRPV4 ion channels have a broad expression profile and were shown to contribute to enhanced pain sensation in inflammation. Directly blocking TRPV4 might run the risk of interfering with normal physiology, and has prompted to explore the interaction with the scaffolding protein AKAP79, an approach successfully used for TRPV1 channels. HEK293t cells express AKAP79, additional transfection did not sensitize human TRPV4. ⋯ A synthetic peptide, resembling these amino acids and extended by a positive region for transmembrane uptake, was tested. Sensitization of TRPV4 responses could be reduced after exposure to this 771-781::TAT peptide but not by a scrambled control peptide. This validates the concept of targeting the interaction between TRPV4 and AKAP79 and controlling increased TRPV4 activity.
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Striatal-enriched phosphatase 61 (STEP61) is a member of intracellular protein tyrosine phosphatases, which is involved in the regulation of synaptic plasticity and a line of neuropsychiatric disorders. This protein tyrosine phosphatase is also abundant in pain-related spinal cord dorsal horn neurons. However, whether and how this tyrosine phosphatase modulates the nociceptive plasticity and behavioral hypersensitivity remain largely unknown. ⋯ To reinstate STEP61 activity, we overexpressed wild-type STEP61 [STEP61(WT)] in spinal dorsal horn, finding that STEP61(WT) completely blunted LTP induction. Behavioral tests showed that LTP blockade by STEP61(WT) correlated with a long-lasting alleviation of thermal hypersensitivity and mechanical allodynia induced by chronic constriction injury of sciatic nerves. These data implicated that STEP61 exerted a negative control over spinal nociceptive plasticity, which might have therapeutic benefit in pathological pain.
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The visual system classifies objects into categories, and distinct populations of neurons within the temporal lobe respond preferentially to objects of a given perceptual category. We can also classify the objects we recognize with the sense of touch, but less is known about the neuronal correlates underlying this cognitive function. To address this question, we performed a multivariate pattern analysis (MVPA) of functional magnetic resonance imagining (fMRI) activity to identify the cortical areas that can be used to decode the category of objects explored with the hand. ⋯ Importantly, we found that categories can also be decoded from the lateral occipital complex (LOC), which is a multimodal region known to be related to the representation of object shape. Furthermore, a hyperalignment analysis showed that activity patterns are similar across subjects. Our results thus indicate that tactile object recognition generates category-specific patterns of activity in a multisensory area known to encode objects, and that these patterns have a similar functional organization across individuals.
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The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. Intracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7days (d). ⋯ To observe in vitro angiogenesis, rat brain microvascular endothelial cells (RBMECs) were incubated under oxygen glucose deprivation (OGD) for 6h (h) and treated with Shh/anti-VEGF. We found that (1) Shh improved neurological scores and reduced infarct volume, which was blocked by Cyclopamine, (2) Shh improved the microvascular density and promoted angiogenesis and neuron survival in the ischemic boundary zone, (3) Shh enhanced VEGF expression and VEGF antibody could reverse angiogenic and protective effect of Shh in vivo and in vitro. These data demonstrate that the administration of Shh protein could protect brain from ischemic injury, in part by promoting angiogenic repair.
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The intrinsic value of an action refers to the inherent sense that experiencing a behavior is enjoyable even if it has no explicit outcome. Previous research has suggested that a common valuation mechanism within the reward network may be responsible for processing the intrinsic value of achieving both the outcome and external rewards. However, how the intrinsic value of action is neurally represented remains unknown. ⋯ The results showed that the stopwatch game with the action-outcome contingency evoked a greater degree of enjoyment because the participants chose this condition over those that lacked such a contingency. The ventral striatum and midbrain were activated only when action-outcome contingency was present. Thus, the intrinsic value of action was represented by an increase in ventral striatal and midbrain activation.