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

描述（由申请人提供）：六层新皮层的出现是哺乳动物大脑进化的标志之一。新皮层的一个重要特征是它在一生中不断变化的能力。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，它允许新皮层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。虽然我们意识到发育中的皮层具有高度的可塑性，但它在受伤或极端环境饲养条件下可以改变和恢复的限度仍然没有完全了解。这个R21建议的目标是：1）确定整个皮质片在发育早期组织严重丧失后能够重新组织和恢复的程度; 2）确定皮质丧失或损伤后恢复能力降低的发育阶段;以及3）量化长时间暴露于高度特定的视觉环境可以影响发育中的皮层的组织和连接的程度，最终影响正常人和脑损伤患者的行为。在短尾负鼠的这些实验中，将在丘脑皮质传入到达皮质之前或在丘脑皮质神经支配皮质之后立即进行视觉皮质的双侧消融。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病变动物的影响，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可塑性的极限，并了解个体可以从新皮层的早期大损伤中恢复的程度。我们的研究结果将在不同发育时间点发生的损伤恢复的预后方面产生重大的临床影响，以及促进早期皮质损伤儿童恢复的康复策略。 公共卫生相关性：本研究的目的是确定在新生儿视觉皮层损伤后，皮层及其产生的行为可以恢复到何种程度。通过在增强的视觉环境中饲养动物，我们希望推动脑损伤动物的恢复极限，并最终在这些个体中产生正常的视觉介导行为。这些研究对早期皮质损伤或创伤的儿童具有重要意义，有助于预后，并影响促进康复的康复策略。

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.