Synaptic plasticity in young versus aged visual cortex

描述（由申请人提供）：在出生后发育过程中观察到的眼优势可塑性下降以前被认为是不可逆的。眼优势可塑性的发育下降限制了成年人视觉系统从慢性单眼剥夺中恢复的能力。在这里，我们使用慢性单眼剥夺从眼睛开放到成年期，以诱导严重的弱视在有色Long Evans大鼠，并证明，黑暗暴露在成年期促进经验依赖性恢复的空间敏锐度在慢性剥夺的眼睛。我们建议，在成年期的黑暗暴露重新激活丘脑皮层突触的解剖和生理可塑性，并描绘了一系列的实验，以隔离，表征和优化丘脑皮层突触传递的恢复。我们认为，黑暗暴露将增强丘脑皮层突触的可塑性，这将促进经验依赖的视觉感知学习和视觉诱发反应的活动依赖性增强。重要的是，我们提出，增强GABA能抑制与地西泮将阻止这些重新激活的解剖，生理和行为可塑性的黑暗暴露。我们建议开发非侵入性的方法，以加强丘脑皮质突触在体内，通过视觉强直（光LTP）和视觉感知学习。此外，我们建议利用经验依赖性增强的丘脑皮层突触是重新激活黑暗暴露，以加速恢复空间敏锐度在我们的严重弱视的动物模型。

DESCRIPTION (provided by applicant): The decline in ocular dominance plasticity observed over the course of postnatal development was previously thought to be irreversible. The developmental decline in ocular dominance plasticity constrains the ability of the adult visual system to recover from chronic monocular deprivation. Here we use chronic monocular deprivation from eye opening to adulthood to induce severe amblyopia in pigmented Long Evans rats, and demonstrate that dark exposure in adulthood promotes the experience-dependent recovery of spatial acuity in the chronically-deprived eye. We propose that dark exposure in adulthood reactivates anatomical and physiological plasticity at thalamocortical synapses, and delineate a series of experiments to isolate, characterize and optimize the recovery of thalamocortical synaptic transmission. We propose that dark exposure will enhance plasticity at thalamocortical synapses, which will promote experience-dependent visual perceptual learning and activity-dependent potentiation of the visually-evoked responses. Importantly, we propose that the enhancement of GABAergic inhibition with diazepam will block these reactivation of anatomical, physiological and behavioral plasticity by dark exposure. We propose to develop non-invasive methods to strengthen thalamocortical synapses in vivo, via visual tetanus (photic LTP) and visual perceptual learning. In addition, we propose to harness the experience-dependent potentiation of thalamocortical synaptic that is reactivated by dark exposure to accelerate the recovery of spatial acuity in our animal model of severe amblyopia.