New Neurons in the Adult Amygdala

描述（由申请人提供）：在哺乳动物大脑中，海马的齿状回（DG）和吻侧脑室的室下区（SVZ）中发现了成人生成的细胞。科学家们一直专注于这两个脑区，以表征介导成人神经发生的因素，确定新细胞的表型，并揭示其潜在的功能意义。虽然在大脑的其他几个区域也发现了新细胞，但对这些新细胞的形态特征、神经化学表型和功能知之甚少。在本研究中，我们将重点放在杏仁核上，这是一个对感觉处理、信息整合和各种生理和行为功能的调节很重要的大脑区域，它包含成人生成的细胞，但在神经发生领域很少受到关注。我们将使用社会一夫一妻制的雌性草原田鼠（Microtus ochrogaster）作为我们的模型系统，因为田鼠的杏仁核含有成年产生的细胞，它们的增殖速度被社会互动促进，被社会隔离降低，抗有丝分裂药物的治疗减少了杏仁核中的新神经元，抑制了社会依恋的形成。我们的工作假设是，来自同一个体的社会/化学感觉刺激以刺激、时间和区域特异性的方式影响杏仁核神经的发生，成人产生的杏仁核神经元整合到现有的神经回路中，表达某些神经化学表型，并在调节社会行为中发挥功能作用。为了验证这一假设，我们将重点关注杏仁核，以：(1)检查化学感觉刺激在细胞增殖中的作用，(2)揭示这种社会/化学感觉体验增强细胞存活的关键时期，(3)确定这些新细胞的神经形态学和神经化学特征，(4)并检查新杏仁核细胞在社会行为中的作用。这项研究的数据将揭示成年杏仁核的神经发生，并为研究杏仁核神经发生潜力作为神经退行性相关杏仁核缺陷的治疗提供一个起点。

DESCRIPTION (provided by applicant): Adult-generated cells are found in the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) of the rostral lateral ventricle in mammalian brains. Scientists have focused on these two brain areas to characterize the factors mediating adult neurogenesis, determine the phenotypes of the new cells, and reveal their potential functional significance. While new cells are also found in several other brain areas, little is known about the morphological characteristics, neurochemical phenotypes, and functions of these new cells. In this proposal, we focus on the amygdala - a brain area which is important for sensory processing, information integration, and the modulation of a variety of physiological and behavioral functions, and which contains adult-generated cells but has received little attention in the neurogenesis field. We will use the socially monogamous female prairie voles (Microtus ochrogaster) as our model system as the vole's amygdala contained adult-generated cells, their rates of proliferation were facilitated by social interactions and diminished by social isolation, and treatment of an antimitotic drug reduced new neurons in the amygdala and inhibited social attachment formation. Our working hypothesis is that social/chemosensory stimuli from a conspecific affect amygdala neurogenesis in a stimulus-, time- and area-specific manner, adult-generated amygdala neurons integrate into the existing neural circuitry, express certain neurochemical phenotypes, and play a functional role in mediating social behavior. To test this hypothesis, we will focus on the amygdala to (1) examine the role of chemosensory stimuli in cell proliferation, (2) reveal the critical period for such social/chemosensory experience to enhance cell survival, (3) determine the neuromorphological and neurochemical characteristics of these new cells, (4) and examine the role of new amygdala cells in social behavior. Data from this study will shed light into amygdala adult neurogenesis and provide a starting point for the investigation of the amygdala neurogenic potential to be used as treatment for neurodegenerative-related amygdala deficits. PUBLIC HEALTH RELEVANCE: Project Narrative Newly-generated cells in the adult mammalian brains (adult neurogenesis) have the potential to be used as treatment for neurodegenerative diseases. Here we propose to examine adult neurogenesis in the amygdala in the socially monogamous prairie voles to test the hypothesis that social environment affects adult neurogenesis in the amygdala, and newly-generated amygdaloid cells integrate into the neural circuitry and play a functional role in the regulation of social behaviors.