Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA.
J Neurosci. 2012 May 9;32(19):6578-86. doi: 10.1523/JNEUROSCI.6391-11.2012.
Changes in CaMKII-regulated synaptic excitability are a means through which experience may modify neuronal function and shape behavior. While behavior in rodent addiction models is linked with CaMKII activity in the nucleus accumbens (NAc) shell, the key cellular adaptations that forge this link are unclear. Using a mouse strain with striatal-specific expression of autonomously active CaMKII (T286D), we demonstrate that while persistent CaMKII activity induces behaviors comparable to those in mice repeatedly exposed to psychostimulants, it is insufficient to increase AMPAR-mediated synaptic strength in NAc shell. However, autonomous CaMKII upregulates A-type K(+) current (IA) and decreases firing in shell neurons. Importantly, inactivating the transgene with doxycycline eliminates both the IA-mediated firing decrease and the elevated behavioral response to cocaine. This study identifies CaMKII regulation of IA in NAc shell neurons as a novel cellular contributor to the sensitization of cocaine reward.
钙调蛋白激酶 II 调节的突触兴奋性变化是经验可能改变神经元功能和塑造行为的一种方式。虽然啮齿动物成瘾模型中的行为与伏隔核壳中的钙调蛋白激酶 II 活性有关，但形成这种联系的关键细胞适应尚不清楚。使用一种纹状体特异性表达自主激活钙调蛋白激酶 II（T286D）的小鼠品系，我们证明，尽管持续的钙调蛋白激酶 II 活性诱导的行为与反复暴露于精神兴奋剂的小鼠相似，但不足以增加伏隔核壳中 AMPAR 介导的突触强度。然而，自主钙调蛋白激酶 II 上调 A 型钾 (K+) 电流 (IA) 并降低壳神经元的放电。重要的是，用强力霉素使转基因失活消除了 IA 介导的放电减少和可卡因反应的升高。这项研究确定了伏隔核壳神经元中钙调蛋白激酶 II 对 IA 的调节是可卡因奖赏敏化的一个新的细胞贡献者。
