Dendritic sodium channels promote active decorrelation and reduce phase locking to parkinsonian input oscillations in model globus pallidus neurons.
Dendritic sodium channels promote active decorrelation and reduce phase locking to parkinsonian input oscillations in model globus pallidus neurons.
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DOI：
10.1523/jneurosci.6062-10.2011
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发表时间：
2011-07-27
期刊：
影响因子：
--
通讯作者：
Jaeger D
中科院分区：
文献类型：
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作者：
Edgerton JR;Jaeger D
神经元群之间的相关放电存在于整个大脑中，并且通常具有节律性，可观察到局部场电位的振荡波动。尽管有节奏的群体活动被认为对许多大脑区域的正常功能至关重要，但在其他情况下，同步的神经振荡与疾病状态有关。在苍白球（啮齿类动物的GP，与灵长类动物的GPe同源）中，正常动物的成对神经元通常具有不相关的放电，尽管解剖组织表明它们应该接受大量的共同输入。相比之下，在帕金森病（PD）动物模型中观察到相关且有节奏的GP放电。部分基于这些发现，有人提出基底节区功能的一个重要部分是主动去相关，由此冗余信息被压缩。实现主动去相关的机制，以及导致其在PD中失败的变化，是人们非常感兴趣的主题。大鼠GP神经元在其树突中表达快速的瞬时电压依赖性钠通道（NaF通道），在非对称突触附近表达水平最高。我们最近发现树突NaF密度强烈影响模型GP神经元对同步兴奋性输入的反应性。在本研究中，我们使用大鼠GP神经元模型来证明树突NaF通道表达是一种潜在的主动去相关的细胞机制。我们进一步表明，具有较低树突NaF通道表达的模型神经元更倾向于与PD中观察到的振荡突触输入模式相锁。
Correlated firing among populations of neurons is present throughout the brain and is often rhythmic in nature, observable as an oscillatory fluctuation in the local field potential. Although rhythmic population activity is believed to be critical for normal function in many brain areas, synchronized neural oscillations are associated with disease states in other cases. In the globus pallidus (GP in rodents, homolog of the primate GPe), pairs of neurons generally have uncorrelated firing in normal animals despite an anatomical organization suggesting that they should receive substantial common input. By contrast, correlated and rhythmic GP firing is observed in animal models of Parkinson's disease (PD). Based in part on these findings it has been proposed that an important part of basal ganglia function is active decorrelation, whereby redundant information is compressed. Mechanisms that implement active decorrelation, and changes that cause it to fail in PD, are subjects of great interest. Rat GP neurons express fast, transient voltage-dependent sodium channels (NaF channels) in their dendrites, with the expression level being highest near asymmetric synapses. We recently showed that the dendritic NaF density strongly influences the responsiveness of model GP neurons to synchronous excitatory inputs. In the present study we use rat GP neuron models to show that dendritic NaF channel expression is a potential cellular mechanism of active decorrelation. We further show that model neurons with lower dendritic NaF channel expression have a greater tendency to phase lock with oscillatory synaptic input patterns like those observed in PD.