Synaptic plasticity in young versus aged visual cortex

描述（由申请人提供）：在动物的一生中，经验调节皮质功能的能力显著降低。在出生后的早期关键时期，单眼剥夺（MD）诱导的双眼神经元的眼优势（OD）的变化，通过迅速减少突触的强度服务剥夺的眼睛。此外，观察到服务于非剥夺眼的突触强度的较慢增加。我们实验室和其他人最近的工作表明，在经典的关键期之后，成年人也可以诱导眼优势转移，但需要更长的MD期。在成年人中，剥夺只涉及缓慢的组成部分，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，并表明有趣的可能性，调节OD可塑性的机会也可能持续一生。我们的初步实验验证了这一假设，并表明，视觉剥夺，通过黑暗暴露（DE），重新激活快速的青少年一样的OD可塑性单眼剥夺。在黑暗暴露后诱导的OD偏移是由于服务于剥夺眼的突触的强度快速下降，以前仅在青少年中描述，以及服务于非剥夺眼的突触的强度快速增加，其通常在青少年和成年人中发展缓慢。拟议的实验研究黑暗暴露的时间要求和功能后果，并使用一组转基因和药理学操作来测试黑暗暴露降低视觉皮层抑制的假设，允许返回到一个更具可塑性的，少年般的状态。此外，我们测试的假设，DE将增加成功的恢复功能的眼睛从出生就被剥夺了视力。这种恢复哺乳动物皮层中经验依赖性突触可塑性的非侵入性方法具有很大的治疗潜力，因为人类弱视导致的视觉缺陷通常在10岁时是不可逆的。

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.