Controlling synaptic and intrinsic plasticity underlying visual cortical enhancement

控制视觉皮层增强的突触和内在可塑性

• 批准号: 10528014
• 负责人: Ming-fai Fong
• 金额: $ 24.9万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10528014
• 关键词: Acute; Address; Affect; Amblyopia; Animal Model; Animals; Automobile Driving; Bilateral; Blindness; Brain; Brain Diseases; Brain Injuries; Calcium; Cells; Chemosensitization; Clinical; Data; Development; Electrophysiology (science); Experimental Designs; Eye; Feedback; Felis catus; Functional disorder; Future; Goals; Hour; Human; Injury; Intervention; Knowledge; Lead; Life; Long-Term Potentiation; Measures; Membrane; Mental Depression; Mentors; Modality; Monitor; Mus; Nature; Neurologic; Neuronal Plasticity; Neurosciences Research; Ocular Dominance; Outcome; Play; Process; Property; Public Health; Quality of life; Recovery; Research; Retina; Role; Sensory; Sensory Process; Slice; Synapses; Synaptic plasticity; System; Testing; Thalamic structure; Time; Translating; Update; Vision; Visual; Visual Cortex; Visual impairment; Work; area striata; cell type; design; disability; early childhood; experience; experimental study; in vivo imaging; infancy; insight; monocular deprivation; nervous system development; nervous system disorder; neural circuit; neuromechanism; optogenetics; postnatal; relating to nervous system; response; sensory cortex; statistics; treatment strategy

Amblyopia is widespread form of human visual disability caused by a disparity in visual quality between the two eyes during early postnatal life. This disparity drives ocular dominance plasticity in the visual cortex to favor the stronger eye at the expense of the weaker (amblyopic) eye. Consequently, synapses in the visual cortex downstream of the amblyopic eye are weakened, a process that is difficult to reverse unless treatment is initiated during infancy or early childhood. Recent work in animal models has suggested several strategies for promoting recovery from amblyopia. While the pathophysiology underlying amblyopia has been well studied, the synaptic, cellular, and circuit changes underlying recovery are less clear. This proposal focuses on a treatment strategy that rapidly promotes visual recovery following experimental amblyopia via temporary inactivation of the retinas. A temporary period of retinal inactivation leads of a stable enhancement of visual cortical responses once vision is restored. The previous mentored research focused on understanding how retinal inactivation promotes recovery at through synaptic and cellular plasticity in the primary visual cortex. The current proposal shifts the focus to how recovery manifests in the statistics of neural activity within visual circuits, and whether this recovery can be controlled through reproducing these activity regimes. The long- term objective of this research is to understand how cortical plasticity is engaged to promote recovery and to inform clinical interventions for treating human amblyopia.

弱视是人类视力残疾的一种普遍形式，其原因是视力与视力之间的视觉质量差异。 出生后早期的两只眼睛。这种差异驱动了视觉皮层中的眼优势可塑性， 以较弱（弱视）的眼睛为代价来支持较强的眼睛。因此，视觉神经元中的突触 弱视眼下游的皮质被削弱，这一过程难以逆转，除非 在婴儿期或幼儿期开始治疗。最近的动物模型研究表明 促进弱视康复的几种策略。虽然弱视的病理生理学基础 虽然已经有了很好的研究，但恢复背后的突触、细胞和电路变化还不太清楚。这 一项提案的重点是一种治疗策略，在实验性视力恢复后迅速促进视力恢复。 视网膜暂时失活导致的弱视。暂时的视网膜失活导致 一旦视力恢复，视觉皮层反应稳定增强。以前的研究指导 专注于了解视网膜失活如何通过突触和细胞 初级视觉皮层的可塑性。目前的建议将重点转移到复苏如何体现在 视觉回路内神经活动的统计数据，以及这种恢复是否可以通过 复制这些活动机制。这项研究的长期目标是了解大脑皮层 可塑性被用于促进恢复并为治疗人类弱视的临床干预提供信息。