Block of inferior olive gap junctional coupling decreases Purkinje cell complex spike synchrony and Rhythmicity
Block of inferior olive gap junctional coupling decreases Purkinje cell complex spike synchrony and Rhythmicity
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DOI：
10.1523/jneurosci.3677-05.2006
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发表时间：
2006-02-08
影响因子：
5.3
通讯作者：
Lang, EJ
中科院分区：
文献类型：
--
作者：
Blenkinsop, TA;Lang, EJ
下橄榄核(IO)神经元通过缝隙连接电连接。这种耦合被认为是浦肯野细胞中橄榄小脑系统产生同步复合峰(CS)活动的基础，也被认为是IO神经元产生自发振荡活动所必需的。橄榄球小脑活动的这些特征被认为是该系统在运动协调中的核心作用。然而，IO神经元之间的缝隙连接耦合与同步和节律性CS活动的关系从未被直接测试过。因此，为了解决这个问题，从小腿2a浦肯野细胞获得了多个电极记录，并向IO中注射了缝隙连接阻滞剂甘苯氧酮。Carbenoxolone总体上将CS的同步性降低了50%，但在一些实验中，>；减少了80%。Carbenoxolone还使平均放电频率降低了50%，这表明电耦合是IO神经元的重要兴奋来源。此外，Carbenoxolone导致CS活动的节律性降低，这种降低与注射降低CS同步性的程度有关。最后，甘草酮被发现逆转或阻止通常由向IO内注射GABA(A)和谷氨酸受体拮抗剂而引起的同步性变化，这表明这些药物对CS同步模式的影响需要IO神经元的电耦合。总之，我们的结果提供了直接证据，证明IO神经元的电耦合是同步CS活动的基础，并表明这种耦合在形成IO峰模式的其他方面起着重要作用。
Inferior olivary (IO) neurons are electrotonically coupled by gap junctions. This coupling is thought to underlie synchronous complex spike (CS) activity generated by the olivocerebellar system in Purkinje cells, and also has been hypothesized to be necessary for IO neurons to generate spontaneous oscillatory activity. These characteristics of olivocerebellar activity have been proposed to be central to the role of this system in motor coordination. However, the relationship of gap junction coupling between IO neurons to synchronous and rhythmic CS activity has never been directly tested. Thus, to address this issue, multiple electrode recordings were obtained from crus 2a Purkinje cells, and carbenoxolone, a gap junction blocker, was injected into the IO. Carbenoxolone reduced CS synchrony by 50% overall, but in some experiments, >80% reductions were achieved. Carbenoxolone also reduced the average firing rate by 50%, suggesting that electrical coupling is a significant source of excitation for IO neurons. Moreover, carbenoxolone caused a reduction in the similar to 10 Hz rhythmicity of CS activity, and this reduction was correlated with the extent to which the injection reduced CS synchrony. Lastly, carbenoxolone was found to reverse or prevent changes in synchrony that are normally induced by injection of GABA(A) and glutamate receptor antagonists into the IO, suggesting that the effects of these drugs on CS synchrony patterns require electrical coupling of IO neurons. In sum, our results provide direct evidence that electrical coupling of IO neurons underlies synchronous CS activity, and suggest important roles for this coupling in shaping other aspects of IO spiking patterns.