BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
BDNF-TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
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DOI：
10.1038/ncomms3031
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发表时间：
2013-06-01
影响因子：
16.6
通讯作者：
Minichiello, Liliana
中科院分区：
文献类型：
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作者：
Besusso, Dario;Geibel, Mirjam;Minichiello, Liliana
脑啡肽能纹状体体神经元中脑源性神经营养因子信号传导的生理学知之甚少。皮质BDNF表达水平的变化和/或突变型亨廷顿蛋白（mHdh）诱导的脑源性神经营养因子顺行转运受损被认为是导致早期亨廷顿病中纹状体苍白球神经元脆弱性的原因。虽然一些研究已经证实了改变皮质脑源性神经营养因子信号和纹状体脆弱性之间的联系，但尚不清楚这些影响是否通过脑源性神经营养因子受体TrkB介导，以及它们是直接还是间接的。使用一种新的遗传小鼠模型，在这里，我们表明，脑源性神经营养因子-TrkB信号从脑啡肽能纹状体目标的选择性去除意外地导致自发性和药物诱导的hypersomotion。这与多巴胺D2受体依赖性增加的纹状体蛋白激酶C和MAP激酶激活有关，导致纹状体脑啡肽能神经元的内在激活改变。因此，纹状体体神经元中的脑源性神经营养因子/TrkB信号传导通过蛋白激酶C/MAP激酶途径调节神经元活性以响应兴奋性输入来控制运动行为的抑制。
The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington's disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor-TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway.