Synaptic plasticity in young versus aged visual cortex

年轻与老年视觉皮层的突触可塑性

• 批准号: 8389862
• 负责人: Elizabeth Mary Quinlan
• 金额: $ 30.9万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8389862
• 关键词: Adult; Amblyopia; Animal Model; Behavioral; Chemosensitization; Chronic; Development; Diazepam; Exposure to; Eye; Long-Evans Rats; Methods; Ocular Dominance; Perceptual learning; Physiological; Pigments; Recovery; Rodent Model; Series; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Tetanus; Vision; Visual; Visual Cortex; Visual system structure; aged; experience; in vivo; monocular deprivation; postnatal; research study; response

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.

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转的。眼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。本研究使用从睁眼到成年期的慢性单眼剥夺来诱导色素型Long Evans大鼠的严重弱视，并证明成年期的黑暗暴露促进了慢性被剥夺眼的空间视敏度的经验依赖性恢复。我们提出，成年期的黑暗暴露可以重新激活丘脑皮质突触的解剖和生理可塑性，并描述了一系列的实验来分离、表征和优化丘脑皮质突触传递的恢复。我们认为，黑暗暴露会增强丘脑皮质突触的可塑性，从而促进经验依赖的视觉知觉学习和活动依赖的视觉诱发反应的增强。重要的是，我们提出地西泮增强gaba能抑制作用将阻断黑暗暴露对解剖学、生理和行为可塑性的重新激活。我们建议发展非侵入性方法，通过视觉破伤风和视觉感知学习来增强丘脑皮质突触。此外，我们建议利用经验依赖的丘脑皮质突触增强，该突触在黑暗暴露下被重新激活，以加速严重弱视动物模型的空间锐度恢复。