Neural mechanisms of visual cortex development and plasticity in humans and animal models

视觉皮质的发育对控制视觉的成熟起着重要的作用。众所周知，成年男性的视皮层比女性的大很多，但很少有研究表明，在视觉皮质的发育过程中是否存在性别差异。尽管对大脑其他区域的性别差异的研究表明，女性大脑不仅仅是男性的较小版本，但人们对区分女性和男性视觉皮质的神经生物学机制知之甚少。我们对可能导致视觉皮质性别差异的经验依赖偏见所知更少。视觉是人类的主要感觉，初级视觉皮质是处理视觉信息的30多个皮质区域动态层次结构的第一步。初级视觉皮质的性别差异可能会影响整个系统，影响从敏锐度到阅读的功能。在我的实验室里，我们的长期目标是了解视觉皮质在人的一生中是如何变化的，以及视觉体验在改变皮质结构和视觉功能方面所起的作用。例如，我们现在知道，人类视觉皮质的发育延伸到生命的第四个十年。发展和经验似乎可能对女性和男性的视觉皮质有不同的影响。这项应用的主要目的是比较年龄、性别和视皮层中依赖经验的变化，以确定性别差异何时出现，以及早期经验是否影响这些差异。我们的方法包括动物模型和使用涵盖从出生到老年的各种年龄的死后组织样本库对人类大脑发育的研究。我们感兴趣的是，我们的初步研究发现了雄性和雌性动物的神经生物学和视觉差异，新的研究将确定控制这些性别差异的确切特征。我们还将使用一些新的令人兴奋的工具来分析大数据，以揭开大脑发育过程中发生的复杂变化。本研究的目的是：1)对视觉皮质可塑性标记物的发育进行分类并检验性别差异；2)测量皮质神经类固醇激素并评估其对视觉皮质发育的影响；3)评估早期视觉体验对视觉和视觉皮质性别差异的影响。我们设计了在人类和动物模型中解决这些目标的研究，并使用现代数据分析评估性别差异。这些结果将解决性别、年龄和经验对视觉皮质神经生物学发展的影响。从这些研究中获得的知识将推进有关大脑发育中性别差异的基本NSE问题。这项工作的一个重要好处，也是我的实验室的优先事项，是创造一个多样化和包容性的培训环境，以支持下一代加拿大神经科学家。

Development of the visual cortex plays an important role in controlling the maturation of vision. It is well-known that the mature adult male visual cortex is substantially larger than the female, but few studies have addressed whether there are sex differences in how the visual cortex develops. Although studies of sex differences in other areas of the brain have shown that the female brain is not merely a smaller version of the male, little is known about the neurobiological mechanisms that differentiate the female and male visual cortex. We know even less about experience-dependent biases that might lead to sex differences in the visual cortex. Vision is the dominant sense in humans, and the primary visual cortex is the first step in a dynamic hierarchy of more than 30 cortical areas that process visual information. Sex differences in the primary visual cortex can ripple through that system, affecting functions from acuity to reading. In my laboratory, our long-term goal is to understand how the visual cortex changes across the lifespan and the role that visual experience plays in altering cortical structure and visual function. For example, we now know that the development of the human visual cortex extends into the fourth decade of life. It seems likely that development and experience may have different effects on female and male visual cortex. The main objective of this application is to compare age, sex, and experience-dependent changes in the visual cortex to identify when sex differences emerge and if early experience affects those differences. Our approach includes animal models and studies of human brain development using a library of postmortem tissue samples that cover a range of ages from birth to old age. We are interested in following up on our pilot studies that found neurobiological and visual differences in male and female animals, with new studies to determine the precise features that control those sex differences. We will also use some new and exciting tools for analyzing big data to unpack the complex changes that occur during brain development. The aims of this research are to 1) Classify development of plasticity markers in visual cortex and test for sex differences; 2) Measure cortical neurosteroids and assess their influence on the development of visual cortex; 3) Assess the impact of early visual experience on sex differences in vision and visual cortex. We have designed studies to address these aims in humans and animal models and assess sex differences using modern data analytics. The results will address the influence of sex, age and experience on the neurobiological development of the visual cortex. The knowledge gained from these studies will advance fundamental NSE questions about sex differences in the developing brain. An important benefit of this work, and a priority for my laboratory, is creating a diverse and inclusive training environment to support the next generation of Canadian neuroscientists.