Breeding status and delayed motoneuron maturation in a eusocial mammal

描述（由申请人提供）：在具有复杂社会的动物中，社会信号可以深刻影响行为，生理和神经系统。裸鼹鼠表现出严格的等级社会组织，其中繁殖者对所有非繁殖者占主导地位。最近，社会地位的变化与脊髓运动神经元的晚期分化有关。裸鼹鼠生活在由一个繁殖雌性（女王），一到三个繁殖雄性和一个生殖抑制的下属组成的大群体中。超过95%的下属一生都不会生育。然而，如果繁殖动物死亡，或者从殖民地移走并与异性配偶配对，则从属动物可以成为繁殖动物。这种社会地位的变化导致支配会阴肌的运动神经元数量增加。该项目将：1）通过独立地操纵性腺激素和社会地位来确定哪些因素触发在脊髓中观察到的变化，2）使用细胞类型标记的免疫细胞化学来建立脊髓内细胞的神经化学特性，所述脊髓内的细胞在育种者中成为大运动神经元，以及3）通过逆行追踪来确定在育种者中募集的大运动神经元的靶。裸鼹鼠独特的社会结构和生活史使我们有机会研究成年哺乳动物的神经可塑性，包括脊髓神经元亚型的晚期分化或重新指定。这些信息可用于开发以运动神经元丢失或萎缩为特征的退行性疾病的治疗方法，例如肌萎缩性侧索硬化症（ALS）。

DESCRIPTION (provided by applicant): In animals with complex societies, social signals can profoundly influence behavior, physiology, and the nervous system. Naked mole-rats exhibit a strict hierarchical social organization in which breeders are dominant to all non-breeders. Recently, a change in social status has been linked to what appears to be late differentiation of spinal motoneurons. Naked mole-rats live in large colonies consisting of a single breeding female (the queen), one to three breeding males, and a large cohort of reproductively suppressed subordinates. Over 95% of subordinates will remain reproductively inactive for their entire lives. A subordinate can become reproductive, however, if a breeding animal dies or if it is removed from the colony and paired with an opposite-sex mate. This change in social status causes an increase in the number of motoneurons innervating perineal muscles. This project will: 1) determine which factors trigger the changes observed in the spinal cord by independently manipulating gonadal hormones and social status, 2) establish the neurochemical identity of cells within the spinal cord that become large motoneurons in breeders using immunocytochemistry for cell-type markers, and 3) determine the targets of the large motoneurons recruited in breeders by retrograde tract-tracing. The unique social structure and life history of naked mole-rats give us the opportunity to examine neural plasticity in an adult mammal, including the late differentiation or re-specification of neuron subtype in the spinal cord. This information could be used to develop treatments for degenerative diseases characterized by loss or atrophy of motoneurons, such as amyotrophic lateral sclerosis (ALS).