Generating sexually differentiated motor rhythms

男性和女性大脑中的许多神经元回路在功能上是不同的，但其背后的机制 人们对这些差异知之甚少。这项工作的首要目标是发现发育过程中基因表达的性别依赖性差异如何导致细胞的性分化活动， 神经元和神经回路。中央模式发生器（Central Pattern Generator，CPG）是一种能够自动 产生有节奏的运动模式，是发现运动的一般原理的强大的研究系统。 神经系统功能我们的研究探讨了产生发声运动模式的后脑CPG 非洲爪蟾因为CPG可以在没有感觉输入的情况下产生运动输出，所以它们可以被 容易在离体制剂中研究。副艇长可在离体脑中激活发声侧CPG， 产生与现存动物相似的性别特异性运动模式。CPG雄性化 雄性在幼年时期雄激素水平激增时自然发生，也可以通过实验 在睾酮处理的成年雌性中诱导。该提案有两个具体目标：1）确定基因中的 CPG在性别、发育阶段和/或睾酮之间具有不同的表达模式 暴露，和2）识别CPG神经元的细胞，网络和形态学特性的出现 与性别特异性运动模式的外观相关。为了实现这些目标，我们将进行RNA 在两个实验环境中对CPG前运动神经元进行测序和全细胞记录：自然 发育中的青少年和睾酮治疗的成年女性。这一战略的基本原理是， 在这两种情况下，与男性化相关的特征将是那些最有可能 与CPG功能存在因果关系。通过识别基因和电路特性， 男性化，激素，细胞信号通路和神经元功能之间的新联系可能会被揭示。

Many neuronal circuits in male and female brains are functionally distinct, but the mechanisms underlying these differences are poorly understood. The overarching goal of this work is to discover how hormone-dependent differences in gene expression during development lead to sexually differentiated activity of neurons and neuronal circuits. Central pattern generators (CPGs) are networks that can autonomously generate rhythmic motor patterns and are powerful study systems for discovering general principles of nervous system function. Our research investigates the hindbrain CPG that generates vocal motor patterns of the frog, Xenopus laevis. Because CPGs can generate motor output without sensory input, they can be readily studied in ex vivo preparations. The X. laevis vocal CPG can be activated in isolated brains, generating sex-specific motor patterns similar to those recorded in living animals. CPG masculinization occurs naturally in males during a juvenile surge in androgen levels, and can also be experimentally induced in testosterone-treated adult females. The proposal has two specific aims: 1) identify genes in the CPG with distinct expression patterns that vary between sex, developmental stage, and/or testosterone exposure, and 2) identify the emergence of cellular, network, and morphological properties of CPG neurons that correlate with the appearance sex-specific motor patterns. To achieve these aims we will perform RNA sequencing and whole-cell recordings of CPG premotor neurons in two experimental contexts: naturally developing juveniles, and testosterone-treated adult females. The rationale for this strategy is that CPG characteristics that correlate with masculinization in both contexts will be those that are most likely to have a causal relation to CPG function. By identifying both genes and circuit properties associated with masculinization, novel links between hormones, cell signaling pathways, and neuron function may be revealed.