Breeding status and delayed motoneuron maturation in a eusocial mammal

描述(申请人提供)：在具有复杂社会的动物中，社会信号可以深刻地影响行为、生理和神经系统。裸鼠表现出一种严格的等级社会组织，繁殖者支配着所有非繁殖者。最近，社会地位的变化似乎与脊髓运动神经元的晚期分化有关。裸鼠--大鼠生活在由一只繁殖的雌性(女王)、一到三只繁殖的雄性和一大群繁殖受到抑制的下级组成的大群体中。超过95%的下属将在他们的一生中保持不活跃的生殖状态。然而，如果繁殖的动物死亡，或者如果它被从群体中移出并与异性配偶配对，下属可能会繁殖。这种社会地位的变化导致支配会阴肌肉的运动神经元数量增加。该项目将：1)确定哪些因素通过独立操纵性腺激素和社会地位来触发在脊髓中观察到的变化；2)利用细胞类型标记物的免疫细胞化学来确定脊髓内成为繁育者大型运动神经元的细胞的神经化学特性；以及3)通过逆行追踪确定育种者招募的大型运动神经元的靶标。裸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，如肌萎缩侧索硬化症(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).