Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2(Suppl 2):17213-20. doi: 10.1073/pnas.1200705109. Epub 2012 Oct 8.
Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular "brakes" on critical period plasticity common to sensory and higher order brain areas.
偏好行为通常在生命早期形成,但潜在的神经回路机制尚不清楚。通过适应独特的筑巢行为测定,我们证实了 C57BL/6 小鼠音乐偏好发展的“关键期”。在出生后第 15 天至第 24 天期间进行早期音乐暴露,可以改变它们对安静庇护所的先天偏好,而这种偏好通常在成年后无法改变。相反,急性暴露于丙戊酸钠的成年小鼠或携带 Nogo 受体(NgR(-/-))靶向缺失的成年小鼠揭示了一种强烈的可塑性偏好,与其他系统中观察到的关键期重新开放一致。cFos 表达的成像显示,仅在开放可塑性条件下,内侧前额叶皮层的额前皮质和下额皮质中存在明显的神经元激活,以响应暴露的音乐。在响应纯音暴露时,既没有观察到行为变化,也没有观察到选择性内侧前额叶皮层激活,表明这是一种音乐特异性效应。与音乐偏好的转变同时,旷场中心穿越次数增加,表明可能具有抗焦虑作用。因此,音乐可能为了解小鼠的情绪状态提供了一个独特的窗口,并且可能是对感觉和更高阶脑区共同存在的关键期可塑性的分子“刹车”的有效检测。