Transsynaptic Activity-Dependent Regulation of Axon Branching and Neurotrophin Expression In Vivo
Transsynaptic Activity-Dependent Regulation of Axon Branching and Neurotrophin Expression In Vivo
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DOI：
10.1523/jneurosci.2172-11.2011
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发表时间：
2011-09-07
影响因子：
5.3
通讯作者：
Borjigin, Jimo
中科院分区：
文献类型：
--
作者：
Calinescu, Anda-Alexandra;Liu, Tiecheng;Borjigin, Jimo
两个主要类别的活动依赖性神经可塑性预测不同的后果活动改变电路的反应。赫布可塑性（正反馈）假设神经元活动的改变会导致回路内的平行反应。相反，稳态可塑性（负反馈）预测，改变神经元活动会导致回路内的补偿反应。这些可塑性模式在体内的相对作用尚不清楚，因为在完整的生物体中很难操纵神经元回路。在这项研究中，我们测试了在成年大鼠的上级颈神经节-松果体回路中活动剥夺的体内效应，该回路可以通过将动物暴露于恒定光照下而无创地沉默。我们证明，完全剥夺交感神经活动显着减少松果体中的轴突蛋白的存在，并减少交感神经轴突乔木的密度和厚度。此外，我们证明交感神经不活动消除松果体功能，并显着降低松果体神经营养因子的表达。给予β-肾上腺素能激动剂恢复了突触前和突触后蛋白的表达。此外，通过侧枝发芽，通常看到单侧去神经后的松果体，补偿轴突生长，在神经活动的情况下，被深深地损害。因此，这些数据表明，交感神经轴突终端维持诱导神经营养因子，这可能是通过逆行机制，以保持轴突乔木的完整性，通过正反馈回路的神经活动。相反，通过使用赫布样神经可塑性，沉默但完整的电路进入冬眠模式，其特征是突触前轴突结构减少，突触后神经营养因子表达显著减少。
The two major classes of activity-dependent neuroplasticity predict different consequences of activity alteration on circuit response. Hebbian plasticity (positive feedback) posits that alteration of neuronal activity causes a parallel response within a circuit. In contrast, homeostatic plasticity (negative feedback) predicts that altering neuronal activity results in compensatory responses within a circuit. The relative roles of thesemodesof plasticity in vivo are unclear, since neuronal circuits are difficult to manipulate in the intact organism. In this study, wetested the in vivo effects of activity deprivation in the superior cervical ganglion-pineal circuit of adult rats, which can be noninvasively silenced by exposing animals to constant light. We demonstrated that total deprivation of sympathetic activity markedly decreased the presence of axonal proteins in the pineal and reduced the density and thickness of sympathetic axonal arbors. In addition, we demonstrated that sympathetic inactivity eliminated pineal function and markedly decreased pineal expression of neurotrophins. Administration of beta-adrenergic agonist restored the expression of presynaptic and postsynaptic proteins. Furthermore, compensatory axonal growth through collateral sprouting, normally seen following unilateral denervation of the pineal, was profoundly impaired in the absence of neural activity. Thus, these data suggest that sympathetic axonal terminals are maintained by neural activity that induces neurotrophins, which may act through a retrograde mechanism to preserve the integrity of axonal arbors via a positive feedback loop. Conversely, by using Hebbian-like neuroplasticity, silent yet intact circuits enter a hibernation mode marked by reduction of presynaptic axonal structures and dramatically reduced postsynaptic expression of neurotrophins.