News From The Journal Of Neuroscience

Main Category: Neurology / Neuroscience
Also Included In: Biology / Biochemistry;  Eye Health / Blindness;  Stroke
Article Date: 21 Aug 2008 - 0:00 PDT

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1. Wnt Effects on Growth Cone Microtubules

Silvia A. Purro, Lorenza Ciani, Monica Hoyos-Flight, Eleanna Stamatakou, Eliza Siomou, and Patricia C. Salinas

Wnt family proteins are secreted from target tissues and regulate axonal terminal arborization during development. In the canonical Wnt pathway, Wnt signals through the phosphoprotein Dishevelled, which leads to inhibition of the kinase Gsk3, elevation of β-catenin, and activation of transcription. Purro et al. now describe an unexpected transcription-independent action of Wnt signaling. Wnt3a rapidly slowed axonal growth from cultured mouse dorsal root ganglion neurons, while growth cones grew larger. Rather than splaying out toward the leading edge, microtubules grew transversely in these enlarged growth cones, forming kinks and loops reminiscent of changes that occur during terminal arborization. This effect appeared to be mediated by dissociation of the tumor suppressor protein adenomatous polyposis coli (APC) from the plus ends of microtubules specifically in growth cones, and it required proper functioning of Dishevelled and Gsk3. Knockdown of APC via RNA inhibition mimicked the effects of Wnt3, producing looped microtubules and increasing growth cone size.

2. Hair-Cell Innervation in Zebrafish

Aaron Nagiel, Daniel Andor Ardó, and A. J. Hudspeth

To study synaptogenesis, it is desirable to observe single axons growing and contacting targets in vivo, and then confirm synapse formation using electron microscopy (EM). This has been problematic, however, because the available techniques require coexpression of two labels or can be toxic. Nagiel et al. therefore developed HRP mCherry, a transmembrane fusion protein with an intracellular fluorescent moiety for in vivo visualization and an extracellular horseradish peroxidase that allows visualization by EM. Because the two domains form a single protein, the labeling seen with EM is proportional to that seen fluorescently. Using this technique, the authors examined innervation of hair cells in the lateral line of zebrafish. They show that single afferents innervated multiple hair cells, all of which had the same polarity (i.e., they sense the same direction of water currents). After hair-cell ablation and regeneration, afferents reinnervated hair cells of the same polarity that they originally innervated.

3. Whole-Cell Recordings of Binocular Inputs to V1

Nicholas J. Priebe

Ocular dominance, which measures the relative strength of input that a cortical neuron receives from each eye, has been studied extensively with extracellular electrodes and other spike-rate-dependent measures. Spike rate might not accurately reflect synaptic inputs from each eye, however, because such inputs might not drive the membrane potential to spiking threshold. Priebe demonstrates this by modeling the nonlinear transformation between membrane fluctuations and spiking. He shows that small changes in membrane potential can result in large differences in spiking and thus in increased apparent ocular dominance. Using in vivo whole-cell patch recordings in cat visual cortex, he then demonstrates that more neurons receive synaptic inputs from both eyes (as measured by membrane potential fluctuations) than is suggested by spike rate. In this sense, neurons are less monocular than previously reported. This has relevance for studies of developmental plasticity in which monocular deprivation has been reported to alter ocular dominance.

4. Estradiol-Mediated Neuroprotection

Quan-Guang Zhang, Ruimin Wang, Mohammad Khan, Virendra Mahesh, and Darrell W. Brann

Estradiol is protective against stroke and neurodegeneration associated with Alzheimer's disease (AD) and other neurodegenerative diseases. This week, Zhang et al. identify molecular mechanisms mediating estradiol's neuroprotective effects in rat hippocampal CA1 neurons after cerebral ischemia. In addition to preventing ischemia-induced neuronal death, estradiol increased the expression of Wnt3, activating the Wnt-β-catenin pathway. Nuclear levels of the transcription factor β-catenin were also increased, as was expression of the anti-apoptotic protein survivin, a target of β-catenin. Estradiol also prevented ischemia-induced upregulation of an inhibitor of Wnt signaling, dickkopf-1 (Dkk1), by preventing activation of c-Jun N terminal kinase (JNK) and its substrate, the transcription factor c Jun. A JNK inhibitor mimicked the protective effects of estradiol, whereas exogenous Dkk1 prevented these effects. Dkk1 has been linked to tau hyperphosphorylation in AD, and Zhang et al. show that ischemia also increased phosphorylation of tau, and estradiol and JNK inhibitors blocked this effect.

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Article adapted by Medical News Today from original press release.
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The Journal of Neuroscience is published by the Society for Neuroscience, an organization of more than 38,000 basic scientists and clinicians who study the brain and nervous system.

Source: Sara Harris
Society for Neuroscience