Steroid Hormone Regulation of Brain Plasticity and Vocal Behavior

项目摘要 基础和临床研究始于世纪末，并持续至今， 我们对大脑恢复力的看法。大脑可塑性这个术语经常被用来描述大脑中的适应性变化。 成人大脑这个拟议的研究计划涉及在季节性背景下的神经可塑性研究。这 这种现象涉及自然发生的大脑变化，使动物能够科普季节性变化， 促进生存和繁殖成功的物质和社会环境。我们研究类固醇 在季节性繁殖中，睾丸激素调节大脑的变化和相关的行为变化 雄性和雌性金丝雀这些鸟拥有一个明确的神经回路，称为歌曲系统， 调节着一种重要的习得性社会行为，歌曲。歌曲因季节而异，因为它更常见， 在春天，当它主要由雄性来吸引雌性时，它会变得更加复杂。雌性也会唱歌 但是以较低的速率和较简单的结构。关键的前脑鸣唱核团在春天的体积要大得多， 男性比在秋季时，歌曲是生产频率较低，这些歌曲核体积也较大的男性 而不是女性。大脑和行为的这种季节性变化可能概括了行为和大脑的可塑性 在学习声乐的过程中发生的。我们最近对金丝雀的研究表明，睾丸激素在 一种多效性的方式，通过在大脑中产生解剖学上的特异性效应来调节鸣唱行为的多个方面。 在前脑鸣唱核团和内侧视前区，睾酮可以诱导男性样的变化， 成年雌性金丝雀的神经发生和歌唱行为，但显然不能诱导完整的性别 逆转，最后是神经元周围网（细胞外基质的专门结构）中的物种变异 与成年人声音可塑性的物种差异有关。在本提案中，我们利用这些发现， 探讨类固醇激素对脑可塑性的调节及与之相关的歌曲学习和行为 以及它们行动中的性别差异。该提案分为四个目标。在《目标一》中，我们问， 雄鼠和雌鼠的鸣唱控制核中类固醇激素诱导的可塑性相似。Aim II调查 睾酮对歌曲行为和与歌曲相关的大脑活动的间接影响 内侧视前核的作用间接促进了与歌曲相关的即刻早期基因表达， 歌曲控制电路中的歌唱行为。目标三解决了成人功能的关键问题 鸣禽的神经发生，因为我们将使用聚焦X射线以特定的方式消融成神经细胞， 射线照射方法在脑室区在睾酮治疗的男性和女性金丝雀，并评估 这些消融的形态和行为后果。在目标四中，我们将检验以下假设： 神经元周围网络在限制大脑和行为可塑性方面起着重要作用，因为它适用于歌曲学习。 这项研究将有助于对大脑可塑性的更多机械见解的发展， 我们确定类固醇激素如何以神经保护和/或认知增强剂样方式起作用。

Project Summary Basic and clinical research that was initiated in the late 20th century and continues to this day has transformed our thinking about brain resilience. The term brain plasticity is often invoked to describe adaptive changes in the adult brain. This proposed research program concerns the study of neuroplasticity in a seasonal context. This phenomenon involves naturally occurring brain changes that allow an animal to cope with seasonal variation in the physical and social environment to facilitate survival and reproductive success. We study how the steroid hormone testosterone regulates brain changes and the associated changes in behavior in seasonally breeding male and female canaries. These birds possess a well-defined neural circuit, called the song system, which regulates an important learned social behavior, song. Song varies seasonally in that it is more common and more complex in spring when it is produced primarily by males to attract females. Females also produce song but at a lower rate with simpler structure. Key forebrain song nuclei are much larger in volume in the spring in males than in the fall when song is produced less frequently; these song nuclei volumes also are larger in males than in females. Such seasonal changes in brain and behavior may recapitulate behavioral and brain plasticity that occurs during the vocal learning process. Our recent work in canaries has shown that testosterone acts in a pleiotropic manner to regulate multiple aspects of song behavior by having anatomically specific effects in the forebrain song nuclei and in the medial preoptic area, that testosterone can induce male-like changes in neurogenesis and in song behavior in adult female canaries but apparently cannot induce a complete sex reversal, and finally that species variation in perineuronal nets (specialized structures of the extracellular matrix) correlates with species variation in adult vocal plasticity. In this proposal, we capitalize on these findings by investigating the regulation by steroid hormones of brain plasticity and the related song learning and behavior as well as sex differences in their action. The proposal is organized into four aims. In Aim I we ask whether steroid hormone-induced plasticity in the song control nucleus is similar in males and females. Aim II investigates indirect effects of testosterone on song behavior and brain activity related to song by assessing how steroid action in the medial preoptic nucleus indirectly facilitates song-related immediate early gene expression and singing behavior in the song control circuit. Aim III addresses the critical question of the function of adult neurogenesis in songbirds as we will ablate neuroblasts in a site-specific manner with the use of the focused X- ray irradiation method in the ventricular zone in testosterone-treated male and female canaries and assess the morphological and behavioral consequences of these ablations. In Aim IV we will test the hypothesis that perineuronal nets play an important role in limiting brain and behavioral plasticity as it applies to song learning. This research will contribute to the development of more mechanistic insights into brain plasticity as well as help us identify how steroid hormones might serve in a neuroprotective and/or cognitive enhancer-like manner.