Controlling synaptic and intrinsic plasticity underlying visual cortical enhancement

弱视是人类普遍存在的一种视觉残疾形式，其原因是 出生后早期有两只眼睛。这种差异驱使视觉皮质中的眼睛优势可塑性 偏爱较强的眼睛，而牺牲较弱(弱视)的眼睛。因此，视觉上的突触 弱视眼睛下游的皮质被削弱，这一过程很难逆转，除非 治疗在婴儿期或儿童早期开始。最近在动物模型上的研究表明 促进弱视康复的几个策略。而弱视背后的病理生理学 已经得到了很好的研究，但对潜在的恢复过程中的突触、细胞和回路的变化还不太清楚。这 提案的重点是一种治疗策略，可在实验性视力恢复后迅速促进视力恢复 由于视网膜暂时失活而导致的弱视。视网膜暂时失活期导致 视力恢复后，视觉皮质反应的稳定增强。以前的指导性研究 重点了解视网膜失活如何通过突触和细胞促进AT的恢复 初级视皮层的可塑性。目前的提案将重点转移到经济复苏如何体现在 视觉回路内神经活动的统计，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质 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。

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.