Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry.
Trace Eyeblink Conditioning in Mice Is Dependent upon the Dorsal Medial Prefrontal Cortex, Cerebellum, and Amygdala: Behavioral Characterization and Functional Circuitry.
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DOI：
10.1523/eneuro.0051-14.2015
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发表时间：
2015-07
期刊：
影响因子：
3.4
通讯作者：
Chitwood RA
中科院分区：
文献类型：
--
作者：
Siegel JJ;Taylor W;Gray R;Kalmbach B;Zemelman BV;Desai NS;Johnston D;Chitwood RA
微量眨眼调节对于研究学习和记忆中多个大脑区域的相互作用非常有用。当前工作的目标是确定在没有诱发惊吓反应和支持这种学习的大脑回路的情况下，是否可以在小鼠模型中建立微量眨眼条件反射。我们在这里表明，当小鼠头部受到限制并允许在轮子上自由奔跑时，它们可以获得无惊吓的微量条件反应（tCR）。大多数小鼠 (75%) 可以以 250 毫秒的跟踪间隔进行学习。由于 tCR 没有受到惊吓相关成分的污染，因此我们能够记录小鼠中 tCR 的发育和时间，以及它们的长期保留（7 和 14 天）和灵活表达（消退和重新获得）。为了确定所涉及的电路，我们对内侧前额叶皮层（mPFC）进行了限制性损伤，结果发现学习受到阻碍。此外，用蝇蕈醇灭活小脑完全消除了 tCR，这表明习得反应是由小脑驱动的。最后，经过训练的动物中 mPFC 和杏仁核的失活几乎使 tCR 失效。这些关键区域的解剖数据表明，mPFC 和杏仁核均投射到基底脑桥头侧，并与眼睑相关的脑桥小脑神经元重叠。这些数据首次报告了小鼠的微量眨眼条件反射，其中 tCR 由小脑驱动，并且需要 mPFC 的局部区域来获取。这些数据进一步揭示了杏仁核向小脑提供条件刺激相关输入的特定作用。
Trace eyeblink conditioning is useful for studying the interaction of multiple brain areas in learning and memory. The goal of the current work was to determine whether trace eyeblink conditioning could be established in a mouse model in the absence of elicited startle responses and the brain circuitry that supports this learning. We show here that mice can acquire trace conditioned responses (tCRs) devoid of startle while head-restrained and permitted to freely run on a wheel. Most mice (75%) could learn with a trace interval of 250 ms. Because tCRs were not contaminated with startle-associated components, we were able to document the development and timing of tCRs in mice, as well as their long-term retention (at 7 and 14 d) and flexible expression (extinction and reacquisition). To identify the circuitry involved, we made restricted lesions of the medial prefrontal cortex (mPFC) and found that learning was prevented. Furthermore, inactivation of the cerebellum with muscimol completely abolished tCRs, demonstrating that learned responses were driven by the cerebellum. Finally, inactivation of the mPFC and amygdala in trained animals nearly abolished tCRs. Anatomical data from these critical regions showed that mPFC and amygdala both project to the rostral basilar pons and overlap with eyelid-associated pontocerebellar neurons. The data provide the first report of trace eyeblink conditioning in mice in which tCRs were driven by the cerebellum and required a localized region of mPFC for acquisition. The data further reveal a specific role for the amygdala as providing a conditioned stimulus-associated input to the cerebellum.