Developmental noise aids robust motor pattern generation and behavior

异步昆虫飞行是在可变条件下产生鲁棒运动模式的一个主要例子。在果蝇中，运动神经元激活序列所需的强大而可调的翅膀功率生产是由一个小的中央模式生成（CPG）网络，由五个电耦合的运动神经元，MN 1 -5。P6的动机是最近的两个发现，提出了关于这个系统的发展问题：第一，正确的CPG输出需要平衡的突触输入MN 1 -5。我们以前表明，正确平衡的兴奋性和抑制性输入到一个单一的MN树突的概率竞争的发展，但它仍然是未知的正确的突触输入平衡如何在MN 1 -5合奏发展。其次，我们对RobustCircuit的初步数据表明，CPG功能需要MN 1 -5对之间的差分电耦合权重以及所有五个MNs的同等调节的膜兴奋性，尽管离子通道表达差异很大。 这些不精确性如何影响CPG发育和功能的稳健性尚不清楚。关于第一个开放的问题，我们假设MN 1 -5获得相等比例的兴奋性突触输入通过向突触生长和竞争，这两者都是基于固有的噪声分支和突触形成。关于第二个开放的问题，我们假设，不精确的离子通道调节有助于强大的调谐MN兴奋性。此外，与P7合作，我们提出，成熟的CPG需要发射模式的不精确性，以重新建立首选MN发射序列扰动。 当这些研究结束时，我们将描述内在的不精确发展和神经元特性如何导致刻板的电路输出和鲁棒的行为。

Asynchronous insect flight is a prime example for robust motor pattern generation under variable conditions. In Drosophila, the motoneuron activation sequences required for robust yet adjustable wing power production are produced by a small central pattern generating (CPG) network that is comprised of five electrically coupled motoneurons, MN1-5. P6 is motivated by two recent discoveries that raise questions about the development of this system: First, correct CPG output requires balanced synaptic input to MN1-5. We previously showed that correctly balanced excitatory and inhibitory input to a single MN dendrite develops from probabilistic competition, but it remains unknown how the correct synaptic input balance across the MN1-5 ensemble develops. Second, our preliminary data for RobustCircuit show that CPG function requires differential electrical coupling weights between MN1-5 pairs and equally tuned membrane excitabilities of all five MNs, although ion channel expression is considerably variable. How these imprecisions affect robustness of CPG development and function is unknown. Regarding the first open question, we hypothesize that MN1-5 acquire equal proportions of excitatory synaptic input through synaptotropic growth and competition, both of which are based on intrinsically noisy branching and synapse formation. Regarding the second open question, we hypothesize that imprecise ion channel regulation aids the robust tuning of MN excitability. Moreover, in collaboration with P7, we propose that the mature CPG requires firing pattern imprecision to re-establish preferred MN firing sequences upon perturbation. When these studies are concluded, we will have characterized how intrinsically imprecise development and neuronal properties lead to stereotyped circuit output and robust behavior.