Blenkinsop Timothy A, Lang Eric J
Department of Physiology and Neuroscience, School of Medicine, New York University, New York, New York 10016, USA.
J Neurosci. 2006 Feb 8;26(6):1739-48. doi: 10.1523/JNEUROSCI.3677-05.2006.
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 approximately 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 GABAA 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.
下橄榄核(IO)神经元通过缝隙连接进行电突触耦合。这种耦合被认为是橄榄小脑系统在浦肯野细胞中产生同步复合峰(CS)活动的基础,并且也被假设为IO神经元产生自发振荡活动所必需。橄榄小脑活动的这些特征被认为是该系统在运动协调中发挥作用的核心。然而,IO神经元之间的缝隙连接耦合与同步和节律性CS活动的关系从未得到直接验证。因此,为了解决这个问题,从2a小叶浦肯野细胞获得了多电极记录,并将缝隙连接阻滞剂羧苄青霉素注入IO。羧苄青霉素总体上使CS同步性降低了50%,但在一些实验中,降低幅度超过了80%。羧苄青霉素还使平均放电率降低了50%,这表明电耦合是IO神经元兴奋的一个重要来源。此外,羧苄青霉素导致CS活动约10Hz的节律性降低,并且这种降低与注射减少CS同步性的程度相关。最后,发现羧苄青霉素可以逆转或阻止通常由向IO注射GABAA和谷氨酸受体拮抗剂所诱导的同步性变化,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,表明IO神经元的电耦合是同步CS活动的基础,并表明这种耦合在塑造IO放电模式的其他方面发挥重要作用。