Dynamics of the Parkinsonian Striatal Microcircuit: Entrainment into a Dominant Network State
Dynamics of the Parkinsonian Striatal Microcircuit: Entrainment into a Dominant Network State
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DOI：
10.1523/jneurosci.1380-10.2010
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发表时间：
2010-08-25
影响因子：
5.3
通讯作者：
Hernandez-Cruz, Arturo
中科院分区：
文献类型：
--
作者：
Jaidar, Omar;Carrillo-Reid, Luis;Hernandez-Cruz, Arturo
基底神经节回路的神经元同步化在运动编码、程序性记忆储存和习惯形成中起着关键作用。帕金森综合征时纹状体多巴胺（DA）耗竭导致皮质基底神经节环同步异常，导致运动功能障碍。然而，动力学的纹状体微电路异常同步帕金森症的基础是知之甚少。在这里，我们使用了有针对性的全细胞记录，钙成像允许同时记录几十个细胞和分析方法，描述了帕金森病（PD）大鼠模型中DA耗竭后纹状体微回路经历的网络动力学的显着变化：除了基础神经元活动的显着增强外，还观察到频繁的自发同步。矢量化网络动力学的多维还原技术表明，增加同步导致一个占主导地位的网络状态，吸收了大多数自发活动的细胞。异常的同步活动几乎可以被GABA能拮抗剂消除，而GABA能传递的阻断促进了纹状体细胞组装体在优势状态下的参与。最后，多巴胺能受体激动剂能够将神经元从主导状态中解偶联。异常同步和“锁定”到一个主导状态可能代表的基本神经元机制，在微电路水平的运动障碍的基础。
Neuronal synchronization in basal ganglia circuits plays a key role in the encoding of movement, procedural memory storage and habit formation. Striatal dopamine (DA) depletion during Parkinsonism causes abnormal synchronization in corticobasal ganglia loops resulting in motor dysfunction. However, the dynamics of the striatal microcircuit underlying abnormal synchronization in Parkinsonism is poorly understood. Here we used targeted whole-cell recordings, calcium imaging allowing the recording from dozens of cells simultaneously and analytical approaches, to describe the striking alterations in network dynamics that the striatal microcircuit under-goes following DA depletion in a rat model of Parkinson disease (PD): In addition to a significant enhancement of basal neuronal activity frequent periods of spontaneous synchronization were observed. Multidimensional reduction techniques of vectorized network dynamics revealed that increased synchronization resulted from a dominant network state that absorbed most spontaneously active cells. Abnormal synchronous activity can be virtually abolished by glutamatergic antagonists, while blockade of GABAergic transmission facilitates the engagement of striatal cell assemblies in the dominant state. Finally, a dopaminergic receptor agonist was capable of uncoupling neurons from the dominant state. Abnormal synchronization and "locking" into a dominant state may represent the basic neuronal mechanism that underlies movement disorders at the microcircuit level.