Department of Physiology and the Keck Center for Integrative Neurosciences, University of California, San Francisco, CA 94143-0444, USA.
Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19026-31. doi: 10.1073/pnas.1013866107. Epub 2010 Oct 11.
Experience-dependent cortical plasticity has been studied by using loss-of-function methods. Here, we take the complementary approach of using a genetic gain-of-function that enhances plasticity. We show that a constitutively active form of H-ras (H-ras(G12V)), expressed presynaptically at excitatory synapses in mice, accelerates and enhances multiple, mechanistically distinct forms of plasticity in the developing visual cortex. In vivo, H-ras(G12V) not only increased the rate of ocular dominance change in response to monocular deprivation (MD), but also accelerated recovery from deprivation by reverse occlusion. In vitro, H-ras(G12V) expression decreased baseline presynaptic release probability and enhanced presynaptically expressed long-term potentiation (LTP). H-ras(G12V) expression also accelerated the increase following MD in the frequency of miniature excitatory potentials, mirroring accelerated plasticity in vivo. These findings demonstrate accelerated neocortical plasticity, which offers an avenue toward future therapies for many neurological and neuropsychiatric disorders.
已通过使用功能丧失方法研究了经验依赖性皮质可塑性。在这里，我们采用了一种遗传功能获得的互补方法来增强可塑性。我们发现，一种组成型激活形式的 H-ras（H-ras[G12V]）在小鼠的兴奋性突触中表达，可加速和增强发育中的视觉皮层中的多种机制不同的可塑性形式。在体内，H-ras[G12V]不仅增加了对单眼剥夺（MD）的眼优势变化的速率，而且还加速了反向遮盖的恢复。在体外，H-ras[G12V]的表达降低了基础突触前释放概率，并增强了突触前表达的长时程增强（LTP）。H-ras[G12V]的表达还加速了 MD 后微兴奋性电位频率的增加，反映了体内加速的可塑性。这些发现证明了加速的新皮层可塑性，为许多神经和神经精神疾病的未来治疗方法提供了一种途径。
