Department of Integrative Biology and Physiology, UCLA Brain Injury Research Center, University of California, Los Angeles, CA 90095, USA.
Brain Res. 2011 May 4;1388:39-47. doi: 10.1016/j.brainres.2011.02.068. Epub 2011 Mar 5.
We have previously demonstrated that exposure of adult rat to a type of enriched environment, known as 'naturalistic habitat' (NH), induces extensive functional plasticity in the whiskers' representations within the primary somatosensory cortex. Here we have investigated the molecular basis for such functional plasticity involved in this model. Based on the role of BDNF on synaptic plasticity and neuronal growth, the focus of this study is on BDNF and its downstream effectors CREB, synapsin I, and GAP-43. In particular, we determined the effects of natural whisker use during 2, 7 or 28 days exposure to a NH on barrel cortex and hippocampus, as compared to standard cage controls. Naturalistic whisker use resulted in increased levels of mRNAs and proteins for BDNF and its downstream effectors. Level changes for these markers were already detected after 2 days in the naturalistic habitat and grew larger over longer exposures (7 and 28 days). The cerebral cortex was found to be sensitive to the naturalistic habitat exposure at all time points, and more sensitive than the hippocampus to the trimming of the whiskers. Trimming of the whiskers decreased the level of most of the markers under study, suggesting that whiskers exert a tonic influence on plasticity markers that can be further enhanced by naturalistic use. These results implicate BDNF and its downstream effectors in the plasticity induced by the naturalistic habitat. The critical action of experience on molecular substrates of plasticity seems to provide molecular basis for the design of experienced-based rehabilitative strategies to enhance brain function.
我们之前已经证明，成年大鼠暴露于一种称为“自然栖息地”（NH）的丰富环境中，会导致初级体感皮层中胡须代表的广泛功能可塑性。在这里，我们研究了这种模型中涉及的功能可塑性的分子基础。基于 BDNF 在突触可塑性和神经元生长中的作用，本研究的重点是 BDNF 及其下游效应物 CREB、突触素 I 和 GAP-43。特别是，我们确定了在 NH 中暴露 2、7 或 28 天期间自然胡须使用对桶状皮层和海马体的影响，与标准笼对照相比。自然胡须的使用导致 BDNF 及其下游效应物的 mRNA 和蛋白水平增加。在自然栖息地中，这些标记物的水平变化在 2 天后就已经被检测到，并且随着暴露时间的延长（7 和 28 天）而增加。大脑皮层在所有时间点都对自然栖息地暴露敏感，并且比海马体对胡须修剪更敏感。胡须修剪会降低大多数研究标记物的水平，这表明胡须对可塑性标记物施加了一种紧张的影响，而自然使用可以进一步增强这种影响。这些结果表明 BDNF 及其下游效应物参与了自然栖息地诱导的可塑性。经验对可塑性分子基质的关键作用似乎为基于经验的康复策略的设计提供了增强大脑功能的分子基础。
