Synaptic plasticity in young versus aged visual cortex

描述(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转的。眼球优势可塑性的发育下降限制了成人视觉系统从慢性单眼剥夺中恢复的能力。在这里，我们使用从睁眼到成年期的慢性单眼剥夺来诱导有色素的Long Evans大鼠的严重弱视，并证明成年期的暗暴露促进了慢性剥夺眼的空间敏锐度的经验依赖性恢复。我们认为，成年期的黑暗暴露重新激活了丘脑皮质突触的解剖和生理可塑性，并描述了一系列实验来分离、表征和优化丘脑皮质突触传递的恢复。我们认为，黑暗暴露将增强丘脑皮质突触的可塑性，这将促进经验依赖型视觉知觉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，安定对GABA能抑制的增强将阻止暗暴露对解剖、生理和行为可塑性的重新激活。我们建议开发非侵入性的方法来加强体内丘脑皮质突触，通过视觉破伤风和视觉知觉学习。此外，我们建议利用丘脑皮质突触的经验依赖性增强，在我们的严重弱视动物模型中，通过黑暗暴露重新激活丘脑皮质突触来加速空间敏感度的恢复。

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.