Nakhnikian Alexander, Rebec George V, Grasse Leslie M, Dwiel Lucas L, Shimono Masanori, Beggs John M
Program in Neuroscience, Indiana University, Bloomington, Indiana, United States of America; Cognitive Science Program, Indiana University, Bloomington, Indiana, United States of America.
Program in Neuroscience, Indiana University, Bloomington, Indiana, United States of America; Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana, United States of America.
PLoS One. 2014 Mar 11;9(3):e89443. doi: 10.1371/journal.pone.0089443. eCollection 2014.
It has been notoriously difficult to understand interactions in the basal ganglia because of multiple recurrent loops. Another complication is that activity there is strongly dependent on behavior, suggesting that directional interactions, or effective connections, can dynamically change. A simplifying approach would be to examine just the direct, monosynaptic projections from cortex to striatum and contrast this with the polysynaptic feedback connections from striatum to cortex. Previous work by others on effective connectivity in this pathway indicated that activity in cortex could be used to predict activity in striatum, but that striatal activity could not predict cortical activity. However, this work was conducted in anesthetized or seizing animals, making it impossible to know how free behavior might influence effective connectivity. To address this issue, we applied Granger causality to local field potential signals from cortex and striatum in freely behaving rats. Consistent with previous results, we found that effective connectivity was largely unidirectional, from cortex to striatum, during anesthetized and resting states. Interestingly, we found that effective connectivity became bidirectional during free behaviors. These results are the first to our knowledge to show that striatal influence on cortex can be as strong as cortical influence on striatum. In addition, these findings highlight how behavioral states can affect basal ganglia interactions. Finally, we suggest that this approach may be useful for studies of Parkinson's or Huntington's diseases, in which effective connectivity may change during movement.
由于存在多个反复循环,理解基底神经节中的相互作用一直非常困难。另一个复杂之处在于,那里的活动强烈依赖于行为,这表明定向相互作用或有效连接可能会动态变化。一种简化的方法是只研究从皮层到纹状体的直接单突触投射,并将其与从纹状体到皮层的多突触反馈连接进行对比。其他人之前关于该通路有效连接性的研究表明,皮层活动可用于预测纹状体活动,但纹状体活动无法预测皮层活动。然而,这项研究是在麻醉或癫痫发作的动物身上进行的,因此无法知道自由行为可能如何影响有效连接性。为了解决这个问题,我们将格兰杰因果关系应用于自由活动大鼠皮层和纹状体的局部场电位信号。与之前的结果一致,我们发现在麻醉和静息状态下,有效连接性在很大程度上是单向的,即从皮层到纹状体。有趣的是,我们发现在自由行为期间有效连接性变为双向。据我们所知,这些结果首次表明纹状体对皮层的影响可能与皮层对纹状体的影响一样强烈。此外,这些发现突出了行为状态如何影响基底神经节的相互作用。最后,我们认为这种方法可能对帕金森病或亨廷顿病的研究有用,在这些疾病中,有效连接性可能在运动过程中发生变化。