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: 7860535
• 负责人: Elizabeth Mary Quinlan
• 金额: $ 32.12万
• 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 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7860535
• 关键词: A Mouse; Adolescent; Adult; Age; Agonist; Amblyopia; Animals; Birth; Brain-Derived Neurotrophic Factor; Eye; Human; Light; Methods; Mus; Neurons; Ocular Dominance; Pattern; Phosphorylation; Plastics; Research Personnel; Ribosomal RNA; Synapses; Synaptic plasticity; Testing; Therapeutic; Transgenic Organisms; Vision; Visual; Visual Acuity; Visual Cortex; Work; aged; critical period; deprivation; experience; mRNA Expression; monocular deprivation; postnatal; prevent; programs; research study; response; success; visual deprivation

DESCRIPTION (provided by applicant): The ability of experience to regulate the cortical function decreases significantly over the lifetime of an animal. During an early, postnatal critical period, monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons through a rapid decrease in the strength of synapses serving the deprived eye. In addition, a slower increase in the strength of synapses serving the non-deprived eye is observed. Recent work, by our lab and others, demonstrates that ocular dominance shifts can also be induced in adults, after the classical critical period, however longer periods of MD are required. In adults, deprivation engages only the slow component, increasing the strength of synapses serving the non-deprived input. This demonstrates that OD plasticity persists into adulthood, and suggests the intriguing possibility that opportunities to regulate OD plasticity may also persist throughout lifetime. Our preliminary experiments tested this hypothesis, and demonstrate that visual deprivation, through dark exposure (DE), reactivates rapid juvenile-like OD plasticity in response to monocular deprivation. The OD shift induced after dark exposure is due to a rapid decrease in the strength of synapses serving the deprived eye, previously only described in juveniles, and a rapid increase in the strength of synapses serving the non-deprived eye, which typically develops slowly in juveniles and adults. The proposed experiments examine the temporal requirements and functional consequences of dark exposure, and use a battery of transgenic and pharmacological manipulations to test the hypothesis that dark exposure decreases inhibition in the visual cortex, allowing a return to a more plastic, juvenile-like state. In addition, we test the hypothesis that DE will increase the success of regaining function in an eye deprived of vision from birth. Such a non-invasive method to restore experience-dependent synaptic plasticity in the mammalian cortex holds great therapeutic potential, as the visual deficit resulting from amblyopia in humans is often irreversible by age 10.

描述（由申请人提供）：经验调节皮质功能的能力在动物的寿命中大大降低。在产后的早期，单眼剥夺（MD）通过快速降低为剥夺眼睛的突触强度而迅速降低双眼神经元的眼优势（OD）。此外，观察到为非剥夺眼睛的突触强度的增加速度较慢。我们的实验室和其他人最近的工作表明，在经典的关键时期之后，成人也可以引起眼部优势转移，但是需要更长的MD时期。在成年人中，剥夺仅涉及缓慢的成分，增加了为非剥夺输入服务的突触强度。这表明，OD可塑性持续到成年，并表明，调节OD可塑性的机会也可能会持续到整个生命周期中。我们的初步实验检验了这一假设，并证明，通过黑暗暴露（DE），视觉剥夺对单眼剥夺的响应响应于少年样的OD可塑性。黑暗暴露后引起的OD偏移是由于为被剥夺的眼睛的突触强度迅速降低，以前仅在少年中描述，并且迅速增加了服务于非剥夺眼睛的突触强度，通常在少年和成人中缓慢发展。提出的实验检查了黑暗暴露的时间需求和功能后果，并使用一系列转基因和药理操作来检验以下假设，即黑暗暴露会减少视觉皮层的抑制作用，从而恢复到更塑料的幼年状状态。此外，我们检验了DE将在剥夺视力的眼中恢复功能的成功的假设。这种无创的方法是恢复哺乳动物皮质中经验依赖的突触可塑性具有巨大的治疗潜力，因为到10岁时，人类弱视引起的视觉缺陷通常是不可逆的。