Can cortical plasticity and adaptive behavior be amplified by an enhanced visual

描述(申请人提供)：六层新皮质的出现是哺乳动物大脑进化的标志之一。新大脑皮层的一个重要特征是其终生变化的能力。这种可塑性在发育过程中尤其明显。发育可塑性是一个高度适应性的过程，允许新皮质在功能上优化其组织和连接，以匹配动物发育环境的物理参数。虽然我们认识到发育中的皮质具有很高的延展性，但在受伤或极端环境饲养条件下，它可以改变和恢复的极限仍然不完全清楚。该R21建议的目标是：1)确定在发育早期严重丢失组织后，整个皮质层可以重新组织和恢复的程度；2)确定皮质在什么发育阶段失去，或在受损后恢复能力降低；以及3)量化长期暴露在高度特定的视觉环境中可以影响发育中皮质的组织和连接，最终影响正常和脑损伤个体的行为的程度。在短尾负鼠身上的这些实验中，双侧视皮质的消融将在丘脑皮质传入神经到达皮质之前或恰好在丘脑皮质神经支配发生之后进行。动物将在中性或视觉增强的环境中饲养，直到成年。为了确定这种环境对正常和受损动物的影响，将进行行为测试，并在这些相同的动物中确定备用皮质的功能组织和连接。这些实验将使我们能够探索正常发育系统中的可塑性极限，并了解个人可以从早期大的病变恢复到新皮质的程度。我们的研究结果将对发生在不同发育时间点的损伤的康复预后以及促进早期皮质损伤儿童康复的康复策略产生重大的临床影响。 公共卫生相关性：本调查的目标是确定在新生儿损伤到视觉皮质后，大脑皮层及其产生的行为可以恢复的程度。通过在增强的视觉环境中饲养动物，我们希望推动大脑受损动物的恢复极限，并最终在这些个体中产生正常的视觉调节行为。这些研究对遭受早期皮质损伤或创伤的儿童具有重要影响，将有助于预后，并影响促进康复的康复战略。

DESCRIPTION (provided by applicant): The emergence of a six-layered neocortex is one of the hallmarks of mammalian brain evolution. An important feature of the neocortex is its ability to change throughout a lifetime. This plasticity is especially pronounced during development. Developmental plasticity is a highly adaptive process that allows the neocortex to functionally optimize both its organization and connectivity to match the physical parameters of the environment in which an animal develops. While we appreciate that the developing cortex is highly malleable, the limits to which it can be altered and recover following injury, or extreme environmental rearing conditions is still not fully understood. The goals of this R21 proposal are to: 1) determine the extent to which the entire cortical sheet can re-organize and recover following severe loss of tissue very early in development; 2) determine the developmental stage at which the cortex loses, or has a reduced capacity to recover following a lesion; and 3) quantify the extent to which prolonged exposure to a highly specified visual environment can influence the organization and connectivity of the developing cortex, and ultimately the behavior in normal and brain lesioned individuals. In these experiments in short-tailed opossums, bilateral ablations of visual cortex will be made just before thalamocortical afferents reach the cortex or just after thalamocortical innervation of the cortex has occurred. Animals will be reared in either a neutral or visually enhanced environment until adulthood. To determine the effects of this environment in both normal and lesioned animals, behavioral tests will be administered and the functional organization and connectivity of spared cortex will be determined in these same animals. These experiments will allow us to probe the limits of plasticity in normally developing systems as well as to appreciate the extent to which individuals can recover from large early lesions to the neocortex. The results of our studies will have a significant clinical impact in terms of prognosis for recovery from injuries that occur at different developmental time points, and rehabilitation strategies that facilitate recovery in children with early cortical insult. PUBLIC HEALTH RELEVANCE: The goal of the present investigation is to determine the extent to which the cortex and the behavior it generates can recover following neonatal lesions to visual cortex. By rearing animals in an enhanced visual environment, we hope to push the limits of recovery in brain lesioned animals, and ultimately generate normal visually mediated behavior in these individuals. These studies have important implications for children who sustain early cortical lesions or trauma and will aid in prognosis, and impact rehabilitation strategies that facilitate recovery.