Plasticity and variation in brain organization and behaviour

哺乳动物的大脑在一生中都会发生变化，但早期生活经历的影响对大脑的构造方式有着最深远的影响。具体来说，新皮层的连接和组织的变化以及它所指导的行为赋予了哺乳动物（包括人类）巨大的灵活性来适应新环境。这种基于经验的可塑性已经通过增强或剥夺感觉运动经验得到证明，这通常分别放大和缩小相应的身体部位表征。例如，修剪大鼠和小鼠的胡须会导致大脑皮层的胡须萎缩，而前肢的胡须会生长。训练啮齿类动物用前肢去够物体，增加了爪子的代表性。在更大的表征中可能出现的额外神经处理被认为是相应身体部位能力增强的基础。

Mammalian brains change throughout the course of a lifetime, but the impact of early life experience has the most profound effect on how the brain is constructed. Specifically, changes in connectivity and organization of the neocortex and the behavior it directs give mammals (humans included) enormous flexibility to adapt to novel environments. Such experience-based plasticity has been demonstrated by enhancing or depriving sensorimotor experience, which generally enlarges and shrinks corresponding body part representations, respectively. For example, trimming the whiskers of rats and mice causes the cortical whisker representation to shrink and that of the forelimb to grow. Training rodents to reach with their forelimbs enlarges the paw representation. The additional neural processing possible in larger representations is thought to underlie enhanced abilities of the corresponding body parts. Most studies of brain plasticity manipulate one variable at a time (e.g. whisker trimming or reach training). But outside of the laboratory, multiple factors together alter the brain and behavior. The complex interaction of factors shaping brains in the real world points to the need for several complementary lines of inquiry. My research program aims to understand how experience shapes the brain. In this proposal, our objectives are to: (1) Determine the extent to which a given genotype can produce variable cortical phenotypes, i.e., how much can the brain change in one lifetime? (2) Determine how multiple complementary changes in experience common in nature, but so far absent in the laboratory interact to shape brain organization. (3) Measure the magnitude of individual variation in sensorimotor skills and relate this to variation in brain organization. The techniques proposed here are well established, but will be implemented in new ways and combinations. This will be the first examination of neural plasticity combining complementary enhancement of one body part (forelimb) and deprivation of another (whiskers). Forelimb reach training will be far more pervasive and will begin far earlier than any previous study. Together these innovations address fundamental questions about the limits of brain plasticity, the impact of complex environments on brain organization, and the relationship between brain organization and skill. Our inquiries will contribute to neuroscientists' understanding of how brains develop and change. As well as being a fundamental question about the nature of humans and other mammals, how animals adapt to complex, changing environments has implications for their responses to climate change and other human impacts on the environment. For humans, the basic question of how changeable and variable the brain is has implications for education, health and societal attitudes about which parts of behavior are fixed and which are mutable.