A gene-expression-based neural code for food abundance that modulates lifespan.
A gene-expression-based neural code for food abundance that modulates lifespan.
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DOI：
10.7554/elife.06259
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发表时间：
2015-05-12
期刊：
影响因子：
7.7
通讯作者：
Ch'ng Q
中科院分区：
文献类型：
--
作者：
Entchev EV;Patel DS;Zhan M;Steele AJ;Lu H;Ch'ng Q
人们对神经系统内部如何表示环境食物的可得性知之甚少。在这里，我们发现关于食物丰度的定量信息是由保守的TGFβ和5 -羟色胺途径成分的神经元特异性基因表达组合编码的。这些途径之间的串音和自动调节改变了daf-7 （TGFβ）和tph-1（色氨酸羟化酶）基因表达响应的形状、动态范围和群体方差。这些复杂的调控特征为tgf - β和血清素信号传导调节这一多神经元编码的准确性提供了不同的机制：daf-7主要调控基因表达变异性，而tph-1主要调控基因表达反应的动态范围。该编码是功能性的，因为daf-7和tph-1突变双向减弱了食物水平依赖性的寿命变化。我们的研究结果揭示了食物丰富的神经密码，并证明基因表达在神经系统中作为控制长期生理的额外信息处理层。为了最大限度地提高它们的生存机会，动物需要能够感知环境中食物丰富程度的变化，并以适当的方式做出反应。神经系统能够感知来自环境的线索，并协调整个生物体的反应，但目前尚不清楚这是如何导致生物体生物学的长期变化的。在线虫中，两个被称为daf-7和tph-1的基因似乎参与了将食物可获得性的感知与生物体生物学变化联系起来。daf-7基因编码一种激素，而tph-1基因编码一种酶，这种酶能产生一种叫做血清素的神经化学物质。在这里，Entchev, Patel， Zhan等人发现daf-7和tph-1基因在线虫的三对神经元中是活跃的。实验表明，这些神经元共同形成一个回路，传递有关食物丰富程度的信息，从而导致蠕虫寿命的变化。当移除这些基因破坏了这个回路时，蠕虫根据食物供应变化调整寿命的能力就被削弱了，这可能是因为它们无法感知食物。实验还表明，该回路能够自我调节，很大程度上是因为daf-7和tph-1能够相互控制对方的活动。总之，这些结果表明，改变神经元中某些基因的活性，使线虫能够改变它们的生物学，以应对食物供应的变化。大脑中的神经元利用电活动来交流和处理信息，Entchev、Patel、Zhan等人的发现表明，基因活动也可以发挥类似的作用。DOI: http://dx.doi.org/10.7554/eLife.06259.002
How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology. DOI: http://dx.doi.org/10.7554/eLife.06259.001 To maximize their chances of survival, animals need to be able to sense changes in the abundance of food in their environment and respond in an appropriate manner. The nervous system is able to sense cues from the environment and coordinate responses in the whole organism, but it is not clear how this leads to long-term changes in the organism's biology. In nematode worms, two genes called daf-7 and tph-1 appear to be involved in connecting the sensing of food availability with changes in the biology of the organism. The daf-7 gene encodes a hormone, while tph-1 encodes an enzyme that makes a neurochemical called serotonin. Here, Entchev, Patel, Zhan et al. found that daf-7 and tph-1 genes are active in three pairs of neurons in nematode worms. The experiments show that these neurons collectively form a circuit that carries information about the abundance of food, which leads to changes in how long the worms live. When this circuit was disrupted by removing these genes, the worms' ability to adjust their lifespan in response to changes in the availability of food was weakened, likely because they were unable to sense food. The experiments also show that the circuit regulates itself, largely because daf-7 and tph-1 are able to control each-other's activity. Together, these results suggest that changing the activity of certain genes in neurons enables nematode worms to alter their biology in response to changes in the availability of food. Neurons in the brain use electrical activity to communicate and process information and Entchev, Patel, Zhan et al.'s findings imply that gene activity can also perform a similar role. DOI: http://dx.doi.org/10.7554/eLife.06259.002