Socially induced brain cells in adults: fate activity and regulation

描述(申请人提供)：哺乳动物的大脑在成年期产生新神经元的能力有限。然而，环境和荷尔蒙刺激可以增加某些大脑区域的神经生成率，这表明这种刺激最终可能被用于治疗，以促进受损或患病大脑区域的修复，恢复行为功能。电鱼作为成年出生的脑细胞的功能和调节模型具有不同寻常的前景，因为它们控制某些行为的神经电路异常简单，而且它们的大脑表现出异常高的细胞增殖率。在NIMH(R03)资助的先导研究中，研究人员使用电鱼来建立社会环境、糖皮质激素、大脑可塑性和沟通行为之间的联系。具体地说，他们证明了将鱼类配对和将皮质醇植入鱼类都增强了一种名为啁啾的电子通信行为，并增加了控制啁啾行为的大脑区域的细胞增加和放射状胶质纤维密度。在这项研究的第二阶段，研究人员问了四个问题：1)社会诱导细胞的表型命运是什么？在将FISH配对后，他们将用细胞增加(BrdU)、神经元(HU)和神经胶质(GFAP，S100B)分化标志物的抗体共同标记大脑。2)新生细胞在啁啾行为中会变得活跃吗？研究人员将在鱼类受到啁啾刺激后不久，在它们的大脑中共同标记细胞添加标记(BrdU)和一种即刻早期基因蛋白(c-fos)的抗体。3)皮质醇在社会诱导的大脑和行为可塑性中起因果作用吗？研究人员将同时使用社交互动和糖皮质激素受体阻滞剂(RU486)来治疗FISH，然后测试脑细胞增加、放射状胶质纤维密度和鸣叫行为。4)社交中存在的哪些特定刺激在导致大脑和行为可塑性方面最有效？研究人员将在允许不同程度交流的刺激环境中配对鱼类，然后确定大脑的可塑性是否与电子通信信号的接收或产生有关。作为一项地区助学金，这项研究项目还将显著加强本科生研究人员的培训。这些研究将有助于在一个模型系统中建立成年出生的脑细胞的表型、功能和调节，该模型系统有望确定新生细胞如何修改神经回路和行为。在人类中，社会互动促进了脑损伤的恢复，并减缓了神经退化的过程。动物研究表明，社会互动的部分好处可能是通过它对新神经元形成的积极作用而发生的。这项研究试图确定促进新神经元形成的社会互动的具体特征。

DESCRIPTION (provided by applicant): The mammalian brain has a limited ability to generate new neurons during adulthood. However, environmental and hormonal stimuli can increase rates of neurogenesis in certain brain regions, suggesting that such stimuli might eventually be used therapeutically to enhance the repair of damaged or diseased brain regions and restore behavioral function. Electric fish have unusual promise as a model for the function and regulation adult-born brain cells because their neural circuits controlling certain behaviors are unusually simple and well described, and their brains show unusually high rates of cell proliferation. In pilot studies funded by NIMH (R03), the researchers used electric fish to establish links between the social environment, glucocorticoid hormones, brain plasticity and communication behavior. Specifically, they demonstrated that both pairing fish together and implanting fish with cortisol potentiated an electrocommunication behavior termed chirping and increased cell addition and radial glial fiber density in the brain region that controls chirping behavior. In this second stage of the research, the researchers ask four questions: 1) What is the phenotypic fate of socially-induced cells? After pairing fish together, they will co-label brains with antibodies to markers of cell addition (BrdU) and neuronal (Hu) and glial (GFAP, S100B) differentiation. 2) Do newborn cells become active during chirping behavior? The investigators will co-label with antibodies for markers of cell addition (BrdU) and an immediate early gene protein (c-fos) in the brains of fish soon after they are stimulated with chirp-eliciting stimuli. 3) Does cortisol play a causal role in socially-induced plasticity in brain and behavior? The researchers will treat fish simultaneously with social interaction and a glucocorticoid receptor blocker (RU486) and then assay for brain cell addition radial glial fibers density and chirping behavior. 4) What specific stimuli present in social interaction are most effective in causing brain and behavioral plasticity? The researchers will pair fish in stimulus environments that allow for differing degrees of communication and then determine whether brain plasticity is associated with the reception or production of electrocommunication signals. As an AREA grant, this research project would also significantly enhance the training of undergraduate researchers. These studies will help establish the phenotype, functionality, and regulation of adult-born brain cells in a model system that holds promise for determining how newborn cells modify neural circuits and behavior. In humans, social interaction improves the recovery from brain injury and slows the process of neurodegeneration. Animal studies indicate that part of this benefit of social interaction may occur through its positive effect on the formation of new neurons. This research seeks to identify specific features of social interaction that promote new neuron formation.