Dynamic shifts in corticostriatal expression patterns of the immediate early genes Homer 1a and Zif268 during early and late phases of instrumental training
Dynamic shifts in corticostriatal expression patterns of the immediate early genes Homer 1a and Zif268 during early and late phases of instrumental training
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DOI：
10.1101/lm.335006
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发表时间：
2006-09-01
影响因子：
2
通讯作者：
Kelley, Ann E.
中科院分区：
文献类型：
--
作者：
Hernandez, Pepe J.;Schiltz, Craig A.;Kelley, Ann E.
适应性运动动作需要事先了解仪器的意外情况。经过练习，这些动作在本质上可以变得高度自动化。然而，调节这些相关学习形式的分子和解剖学基础尚不清楚。在目前的研究中，我们使用原位杂交来测量两个即刻早期基因(IEGs)的mRNA水平，在一个仪器范式中，大鼠学习杠杆挤压食物。我们报告说，在三次训练后，与未经训练的对照组相比，Hmer la和Zif268(分别是效应者和调节性IEG)在广泛的皮质纹状体网络中被显著诱导。然而，随着训练时间的延长(23节)，这两个基因的表达模式发生了明显的变化。在额叶和扣带回皮质，Hmer 1a(官方代码Hmer 1)的表达显著减少，而纹状体的表达总体上保持不变。有趣的是，与早期学习者相比，随着大量训练，Hmer la在纹状体腹外侧区(VLS)的表达显著增加，这表明VLS的可塑性是有效产生学习行为或习惯形成所必需的。Zif268(官方符号Egrf的表达随着广泛的训练而普遍下降；然而，这些变化并不显著。这些结果首次表明，在分子水平上，皮质纹状体系统的作用发生了动态变化，这些系统参与了目标导向反应的早期获得和巩固，而不是那些在广泛训练后参与的人。
Adaptive motor actions require prior knowledge of instrumental contingencies. With practice, these actions can become highly automatic in nature. However, the molecular and anatomical substrates mediating these related forms of learning are not understood. In the present study, we used in Situ hybridization to measure the mRNA levels of two immediate early genes (IEGs) in an instrumental paradigm where rats learned to lever-press for food. We report that after three training sessions, Homer la and Zif268 (an effector and regulatory IEG, respectively) were significantly induced within an extensive corticostriatal network relative to untrained controls. With extended training (23 sessions), however, a shift in the expression patterns of the two genes was evident. Expression of Homer la (official symbol Homer1) decreased significantly in frontal and cingulate cortices, whereas striatal expression was generally maintained. Interestingly, Homer la expression markedly increased with extensive training in the ventrolateral region of the striatum (VLS) relative to early learners, suggesting that plasticity in the VLS is required for the efficient production of the learned behavior or in habit formation. Zif268 (official symbol Egrf expression generally decreased with extensive training; however, these changes were not significant. These results demonstrate for the first time, on a molecular level, a dynamic shift in the contribution of corticostriatal systems mediating the early acquisition and consolidation of goal-directed responses to those engaged after extensive training.