Cell death triggers olfactory circuit plasticity via glial signaling in Drosophila.
Cell death triggers olfactory circuit plasticity via glial signaling in Drosophila.
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DOI：
10.1523/jneurosci.5984-10.2011
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发表时间：
2011-05-25
期刊：
影响因子：
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通讯作者：
Wilson RI
中科院分区：
文献类型：
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作者：
Kazama H;Yaksi E;Wilson RI
果蝇的触角叶被组织成肾小球隔室，在那里嗅觉受体神经元与投射神经元突触。投射神经元树突也接受来自连接肾小球的局部神经元的输入。在这项研究中，我们调查了如何在这个回路中的活动随着时间的推移而变化时，感觉传入在体内被长期删除。在正常回路中，肾小球之间的兴奋性连接很弱。然而，我们长期切断受体神经元轴突投射到一个子集的肾小球，我们发现，气味诱发的横向兴奋性输入到deafferented投射神经元增强了几倍。这至少部分是由于从兴奋性局部神经元到投射神经元的电突触增强，以及兴奋性局部神经元的活动增加。仅仅沉默受体神经元不足以引起这些变化，这意味着切断受体神经元轴突是相关的信号。当我们在切断受体神经元的轴突之前表达神经保护基因Wallerian变性缓慢（WldS）时，这阻止了可塑性的诱导。因为表达WldS阻止了切断的轴突招募神经胶质细胞，这个结果表明神经胶质细胞的作用。与此一致，我们发现，在成鞘胶质细胞中阻断内吞作用阻断可塑性的诱导。总之，这些结果揭示了一种新的损伤反应，其中切断的感觉轴突招募神经胶质细胞，这反过来又向中枢神经元发出信号，以上调其活性。通过加强失去传入神经的大脑区域中神经元之间的兴奋性相互作用，这种机制可能有助于增强活动以补偿失去的感觉输入。
The Drosophila antennal lobe is organized into glomerular compartments where olfactory receptor neurons synapse onto projection neurons. Projection neuron dendrites also receive input from local neurons which interconnect glomeruli. In this study, we investigated how activity in this circuit changes over time when sensory afferents are chronically removed in vivo. In the normal circuit, excitatory connections between glomeruli are weak. However, after we chronically severed receptor neuron axons projecting to a subset of glomeruli, we found that odor-evoked lateral excitatory input to deafferented projection neurons was potentiated several-fold. This was due at least in part to strengthened electrical synapses from excitatory local neurons onto projection neurons, as well as increased activity in excitatory local neurons. Merely silencing receptor neurons was not sufficient to elicit these changes, implying that severing receptor neuron axons is the relevant signal. When we expressed the neuroprotective gene Wallerian degeneration slow (WldS) in receptor neurons prior to severing their axons, this blocked the induction of plasticity. Because expressing WldS prevents severed axons from recruiting glia, this result suggests a role for glia. Consistent with this, we found that blocking endocytosis in ensheathing glia blocked the induction of plasticity. In sum, these results reveal a novel injury response whereby severed sensory axons recruit glia, which in turn signal to central neurons to upregulate their activity. By strengthening excitatory interactions between neurons in a deafferented brain region, this mechanism might help boost activity to compensate for lost sensory input.