Neuron
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To investigate Eph-ephrin bidirectional signaling, a series of mutations were generated in the ephrin-B3 locus. The absence of both forward and reverse signaling resulted in mice with mirror movements as typified by a hopping locomotion. ⋯ Ephrin-B3 is concentrated at the spinal cord midline, while one of its receptors, EphA4, is expressed in postnatal corticospinal neurons as their fibers pathfind down the contralateral spinal cord. Our data indicate ephrin-B3 functions as a midline-anchored repellent to stimulate forward signaling in EphA4-expressing axons.
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Kainate receptors alter the excitability of mossy fiber axons and have been reported to play a role in the induction of long-term potentiation (LTP) at mossy fiber synapses in the hippocampus. These previous studies have relied primarily on the use of compounds whose selectivity is unclear. ⋯ Additionally, short-term synaptic facilitation is impaired in GluR6 knockout mice, suggesting that kainate receptors act as presynaptic autoreceptors on mossy fiber terminals to facilitate synaptic transmission. These data demonstrate that kainate receptors containing the GluR6 subunit are important modulators of mossy fiber synaptic strength.
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G protein-coupled receptor kinase 5 (GRK5) is a member of a family of enzymes that phosphorylate activated G protein-coupled receptors (GPCR). To address the physiological importance of GRK5-mediated regulation of GPCRs, mice bearing targeted deletion of the GRK5 gene (GRK5-KO) were generated. GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine. ⋯ The antinociceptive effect of oxotremorine was also potentiated and prolonged. Muscarinic receptors in brains from GRK5-KO mice resisted oxotremorine-induced desensitization, as assessed by oxotremorine-stimulated [5S]GTPgammaS binding. These data demonstrate that elimination of GRK5 results in cholinergic supersensitivity and impaired muscarinic receptor desensitization and suggest that a deficit of GPCR desensitization may be an underlying cause of behavioral supersensitivity.
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Historical Article
The emergence of modern neuroanatomy and developmental neurobiology.