Nature neuroscience
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Nature neuroscience · Feb 2012
Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy.
Dysfunction of fast-spiking, parvalbumin-positive (FS-PV) interneurons is implicated in the pathogenesis of epilepsy. ErbB4, a key Neuregulin 1 (NRG1) receptor, is mainly expressed in this type of interneurons, and recent studies suggest that parvalbumin interneurons are a major target of NRG1-ErbB4 signaling in adult brain. Thus, we hypothesized that downregulation of NRG1-ErbB4 signaling in FS-PV interneurons is involved in epilepsy. ⋯ Moreover, expression of ErbB4, but not ErbB2, was downregulated in human epileptogenic tissue. Together, our findings suggest that NRG1-ErbB4 signaling contributes to human epilepsy through regulating the excitability of FS-PV interneurons. ErbB4 may be a new target for anticonvulsant drugs in epilepsy.
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Nature neuroscience · Dec 2011
Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction.
Quantitative trait locus mapping of chemical/inflammatory pain in the mouse identified the Avpr1a gene, which encodes the vasopressin-1A receptor (V1AR), as being responsible for strain-dependent pain sensitivity to formalin and capsaicin. A genetic association study in humans revealed the influence of a single nucleotide polymorphism (rs10877969) in AVPR1A on capsaicin pain levels, but only in male subjects reporting stress at the time of testing. ⋯ Additional experiments in mice confirmed the male-specific interaction of V1AR and stress, leading to the conclusion that vasopressin activates endogenous analgesia mechanisms unless they have already been activated by stress. These findings represent, to the best of our knowledge, the first explicit demonstration of analgesic efficacy depending on the emotional state of the recipient, and illustrate the heuristic power of a bench-to-bedside-to-bench translational strategy.
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Right hemisphere dominance for visuospatial attention is characteristic of most humans, but its anatomical basis remains unknown. We report the first evidence in humans for a larger parieto-frontal network in the right than left hemisphere, and a significant correlation between the degree of anatomical lateralization and asymmetry of performance on visuospatial tasks. Our results suggest that hemispheric specialization is associated with an unbalanced speed of visuospatial processing.
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Nature neuroscience · Sep 2011
Erroneous analyses of interactions in neuroscience: a problem of significance.
In theory, a comparison of two experimental effects requires a statistical test on their difference. In practice, this comparison is often based on an incorrect procedure involving two separate tests in which researchers conclude that effects differ when one effect is significant (P < 0.05) but the other is not (P > 0.05). ⋯ An additional analysis suggests that incorrect analyses of interactions are even more common in cellular and molecular neuroscience. We discuss scenarios in which the erroneous procedure is particularly beguiling.
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Nature neuroscience · Aug 2011
Spatial gradients and multidimensional dynamics in a neural integrator circuit.
In a neural integrator, the variability and topographical organization of neuronal firing-rate persistence can provide information about the circuit's functional architecture. We used optical recording to measure the time constant of decay of persistent firing (persistence time) across a population of neurons comprising the larval zebrafish oculomotor velocity-to-position neural integrator. ⋯ This topography is consistent with the emergence of persistence time heterogeneity from a circuit architecture in which nearby neurons are more strongly interconnected than distant ones. Integrator circuit models characterized by multiple dimensions of slow firing-rate dynamics can account for our results.