Cofilin1 controls transcolumnar plasticity in dendritic spines in adult barrel cortex.
Cofilin1 controls transcolumnar plasticity in dendritic spines in adult barrel cortex.
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DOI：
10.1371/journal.pbio.1002070
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发表时间：
2015-02
期刊：
影响因子：
9.8
通讯作者：
Miyashita Y
中科院分区：
文献类型：
--
作者：
Tsubota T;Okubo-Suzuki R;Ohashi Y;Tamura K;Ogata K;Yaguchi M;Matsuyama M;Inokuchi K;Miyashita Y
在感觉剥夺过程中，桶状皮层经历了一个功能柱的扩张，这个功能柱代表了被剥夺的输入（被剥夺的输入），进入邻近的被剥夺的输入（被剥夺的输入），而这些被剥夺的输入依次收缩。结果，被剥夺的神经元同时增加和减少他们对空闲输入和被剥夺输入的反应。先前的研究表明，树突棘在桶状图可塑性过程中被重塑。由于cofilin1是肌动蛋白丝周转的主要调节因子，在体外控制树突棘结构的扩张和收缩，因此假设它在桶状图可塑性中调节这两种反应。然而，这一假设尚未得到验证。利用慢病毒载体，我们在剥夺柱的2/3层神经元中局部敲除cofilin1。使用通道视紫红质-2对cofilin1敲低的神经元进行光遗传学标记，并针对这些敲低的神经元进行电生理记录。我们发现，cofilin1敲低受损的反应在保留输入时增加，而在保留输入时减少，这表明cofilin1依赖性在这两种类型的桶状图可塑性中是分离的。为了探索这种分离的结构基础，我们分析了被剥夺的柱状树突分支上的脊柱密度，这些分支应该接受来自未被剥夺的柱的密集水平跨柱投影。我们发现脊柱数目以依赖于cofilin - 1的方式选择性地在颗粒上层的远端部分增加，这里存在大多数的跨柱性突起。我们的研究结果表明，cofilin - 1介导的肌动蛋白动力学通过水平跨柱回路中发生的树突脊柱重构，以输入特定的方式调节功能图谱的可塑性。这些关于成年大鼠跨柱状可塑性的新机制见解可能对理解比啮齿类动物（如灵长类动物）的新皮层具有更复杂柱状组织的新皮层回路的重组具有普遍意义。在体内对神经元的电生理和形状的测量表明，在连接小鼠须桶的电路中，需要cofilin1来重塑树突棘，从而帮助新皮层的经验依赖可塑性。成人大脑皮层的可塑性是我们学习和记忆的基础。然而，其分子机制尚不清楚。在啮齿类动物的感觉桶状皮层（一种表征新皮层可塑性的良好模型）中，神经元直接编码须的位移——当该桶所代表的须移动时，给定桶内的神经元就会放电。引人注目的是，除了一个晶须外，所有的晶须都被剥夺了，这改变了原始的表征——代表被剥夺输入的皮层柱缩小，而代表未被剥夺输入的皮层柱扩大，侵入周围被剥夺的皮层柱。由于单神经元水平的结构变化被认为与这种可塑性有关，因此我们将重点放在cofilin1上，这是一种已知的调节细胞骨架和调节树突棘结构的蛋白质。我们通过只保留D1晶须来诱导D1柱的经验依赖性可塑性，并敲低D2柱中cofilin1的表达。Cofilin1敲低对可塑性的影响是不同的，因此，经验依赖的多余输入表征的增加受到损害，而缺失输入表征的减少则完好无损。然后我们发现，在这些塑性变化期间，D1和D2柱之间连接周围的树突棘密度以cofilin - 1依赖的方式增加。cofilin1依赖性的密度增加只在皮层的最浅层部分观察到，而在更深的部分没有观察到，这与分别传递保留信息和剥夺信息的轴突的分布模式一致。这些结果表明，cofilin1通过在连接柱的电路中重塑树突棘来调节新皮质功能的可塑性。
During sensory deprivation, the barrel cortex undergoes expansion of a functional column representing spared inputs (spared column), into the neighboring deprived columns (representing deprived inputs) which are in turn shrunk. As a result, the neurons in a deprived column simultaneously increase and decrease their responses to spared and deprived inputs, respectively. Previous studies revealed that dendritic spines are remodeled during this barrel map plasticity. Because cofilin1, a predominant regulator of actin filament turnover, governs both the expansion and shrinkage of the dendritic spine structure in vitro, it hypothetically regulates both responses in barrel map plasticity. However, this hypothesis remains untested. Using lentiviral vectors, we knocked down cofilin1 locally within layer 2/3 neurons in a deprived column. Cofilin1-knocked-down neurons were optogenetically labeled using channelrhodopsin-2, and electrophysiological recordings were targeted to these knocked-down neurons. We showed that cofilin1 knockdown impaired response increases to spared inputs but preserved response decreases to deprived inputs, indicating that cofilin1 dependency is dissociated in these two types of barrel map plasticity. To explore the structural basis of this dissociation, we then analyzed spine densities on deprived column dendritic branches, which were supposed to receive dense horizontal transcolumnar projections from the spared column. We found that spine number increased in a cofilin1-dependent manner selectively in the distal part of the supragranular layer, where most of the transcolumnar projections existed. Our findings suggest that cofilin1-mediated actin dynamics regulate functional map plasticity in an input-specific manner through the dendritic spine remodeling that occurs in the horizontal transcolumnar circuits. These new mechanistic insights into transcolumnar plasticity in adult rats may have a general significance for understanding reorganization of neocortical circuits that have more sophisticated columnar organization than the rodent neocortex, such as the primate neocortex. In vivo measurement of the electrophysiology and shape of neurons reveals that cofilin1 is needed for remodeling dendritic spines in circuits that connect mouse whisker barrels, so aiding experience-dependent plasticity in the neocortex. Plasticity in the adult neocortex is the basis of our learning and memory. However, its molecular mechanisms are still unclear. In the sensory barrel cortex of rodents, a well-characterized model for neocortical plasticity, neurons directly code for whisker displacement—neurons within a given barrel will fire when the whisker that that barrel represents is moved. Strikingly, the deprivation of all but a single whisker alters the original representations—cortical columns representing the deprived inputs shrink and that representing the spared inputs expands, intruding into the surrounding deprived columns. Because single-neuron-level structural changes are suggested to be involved in this plasticity, here we focused on cofilin1, a protein that is known to modulate the cytoskeleton and to regulate the structure of dendritic spines. We induced experience-dependent plasticity in the D1 column by sparing only the D1 whisker, and knocked down the expression of cofilin1 in the D2 column. Cofilin1 knockdown differentially affected plasticity, such that experience-dependent increases in spared input representation were impaired, whereas decreases in deprived input representation were intact. We then found that during these plastic changes, the density of dendritic spines increased in a cofilin1-dependent manner around the connections between the D1 and D2 columns. Cofilin1-dependent density increase was observed only in the most superficial part of the cortex but not in deeper parts, consistent with the distribution patterns of axons that transmit spared and deprived information, respectively. These results suggest that cofilin1 regulates neocortical functional plasticity through the remodeling of dendritic spines within circuits that connect columns.
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