BackgroundItch, chronic itch in particular, can have a significant negative impact on an individual’s quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown.ResultsWe report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine.ConclusionOur results demonstrate a critical role for ERK activation in itch sensation at the spinal level.

Self-avoidance is a mechanism by which dendrites from the same neuron repel one another in order to establish uniform coverage of the dendritic field. The importance of self-avoidance for the development of complex arborization patterns has been highlighted by studies of Drosophila sensory and mouse retinal neurons. However, it is unclear whether branch patterning in the mammalian central nervous system is also governed by this strategy. We reduced Satb2 expression in a population of layer II/III pyramidal neurons in vivo by RNA interference and found that the somas of Satb2-deficient neurons clumped together, and their dendrites failed to expand laterally but instead formed fascicles. Furthermore, experiments showed that reducing Satb2 caused the adhesion of not only neighboring Satb2-deficient neurons but also neighboring wild-type neurons. Our results indicate a cell autonomous and non-cell autonomous role for Satb2 in regulating the adhesive and/or repulsive properties of cerebral pyramidal neurons.

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BackgroundSensory input is generally thought to be necessary for refining and consolidating neuronal connections during brain development. We here report that cortical callosal axons in somatosensory cortex require sensory input for their target selection in contralateral cortex.ResultsEliminating sensory input to either hemisphere by unilateral transection of infraorbital nerve (ION) prevents target selection of callosal axons in contralateral cortex. Strikingly, blocking sensory input bilaterally, by simultaneously transecting both IONs, results in rescued callosal projection. In contrast, non-simultaneous bilateral ION transection has the same effect as unilateral transection. Similar results are obtained by lesion of whisker hair follicles. c-Fos-positive neurons in brain slices treated with KCl is decreased more in contralateral cortex with unilateral removal of sensory input, but decreased similarly in both cortices in mice with simultaneous bilateral removal of sensory input. Frequency of sEPSC of cortical neurons is also reduced in contralateral cortex with the unilateral removal of sensory input, but equally reduced on both sides with the bilateral removal of sensory input, suggesting that unbalanced bilateral sensory input might lead to mismatched neuronal activity between the two cortices and contribute to the formation of callosal projection.ConclusionOur data demonstrate a critical role of balanced bilateral somatosensory input in the formation of callosal connections, and thus reveal a new role of sensory input in wiring brain circuits.

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