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: 7279815
• 负责人: Elizabeth Mary Quinlan
• 金额: $ 32.44万
• 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 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279815
• 关键词: A Mouse; Adolescent; Adult; Age; Agonist; Amblyopia; Animals; Birth; Brain-Derived Neurotrophic Factor; Chromosome Pairing; Eye; Human; Invasive; 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 developmental 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）：在动物的一生中，调节皮质功能的经验能力显着下降。在出生后的早期关键时期，单眼剥夺（MD）通过服务于被剥夺的眼睛的突触强度的快速下降而导致双眼神经元的眼优势（OD）发生转变。此外，观察到服务于非剥夺眼睛的突触强度的缓慢增加。我们的实验室和其他人最近的工作表明，在经典关键期之后，成人也可以诱导眼优势转移，但需要更长的 MD 期。在成年人中，剥夺仅涉及缓慢的部分，从而增加了服务于非剥夺输入的突触的强度。这表明 OD 可塑性持续到成年期，并表明调节 OD 可塑性的机会也可能在一生中持续存在这一有趣的可能性。我们的初步实验验证了这一假设，并证明通过黑暗暴露 (DE) 进行的视觉剥夺会重新激活快速的青少年样 OD 可塑性，以响应单眼剥夺。黑暗暴露后引起的 OD 变化是由于服务于被剥夺眼睛的突触强度迅速下降（之前仅在青少年中描述），以及服务于非剥夺眼睛的突触强度迅速增加，后者通常在幼年发育缓慢。青少年和成人。拟议的实验检查了黑暗暴露的时间要求和功能后果，并使用一系列转基因和药理学操作来测试这样的假设：黑暗暴露会降低视觉皮层的抑制，从而恢复到更具可塑性、类似青少年的状态。此外，我们还检验了这样的假设：DE 将提高先天失明的眼睛恢复功能的成功率。这种恢复哺乳动物皮质中依赖于经验的突触可塑性的非侵入性方法具有巨大的治疗潜力，因为人类弱视导致的视力缺陷通常在 10 岁时就无法逆转。