Lang Eric J
Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.
J Neurophysiol. 2002 Apr;87(4):1993-2008. doi: 10.1152/jn.00477.2001.
Olivocerebellar activity is organized such that synchronous complex spikes occur primarily among Purkinje cells located within the same parasagittally oriented strip of cortex. Previous findings have shown that this synchrony distribution is modulated by the release of GABA and glutamate within the inferior olive, which probably act by controlling the efficacy of the electrotonic coupling between olivary neurons. The relative strengths of these two neurotransmitters in modulating the patterns of synchrony were compared by obtaining multiple electrode recordings of spontaneous crus 2a complex spike activity during intraolivary injection of solutions containing a GABA(A) (picrotoxin) and/or AMPA [1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX)] receptor antagonist. Injection of either antagonist led to increased synchrony between cells located within the same parasagittally oriented approximately 250-microm-wide cortical strip. Picrotoxin also increased complex spike synchrony among cells located in different cortical strips, leading to a less prominent banding pattern, whereas injections of NBQX tended to decrease complex spike synchrony among such cells, enhancing the banding pattern. The relative strength of these two classes of olivary afferents was assessed by first injecting one of the antagonists alone and then in combination with the other. The enhanced banding pattern of complex spike synchrony following injection of NBQX alone remained during the subsequent combined injection of both antagonists. Furthermore, the widespread synchronization of complex spike activity following injection of picrotoxin alone was partially or completely reversed by combined injection of picrotoxin and NBQX. Changes in the climbing fiber reflex induced by the intraolivary injections paralleled the changes observed for spontaneous complex spike activity, indicating that the effects of picrotoxin and NBQX on the synchrony distribution reflect changes in the pattern of effective coupling of inferior olivary neurons and demonstrating that synchronous complex spike activity does not require simultaneous excitatory input to olivary cells. Finally the pattern of synchrony during motor cortical stimulation was examined. It was found that the patterns of synchrony for motor-cortex-evoked complex spike activity were similar to those of spontaneous activity, indicating an important role for electrotonic coupling in determining the response of the olivocerebellar system to afferent input. Moreover, intraolivary injections of picrotoxin increased the spatial distribution of the evoked response. In sum, the results provide evidence for the hypothesis that electrotonic coupling of inferior olivary neurons via gap junctions is the mechanism underlying complex spike synchrony and that this coupling plays an important role in determining the responses of the olivocerebellar system to synaptic input.
橄榄小脑活动的组织方式使得同步复合峰主要出现在位于同一矢状旁向皮质条带内的浦肯野细胞之间。先前的研究结果表明，这种同步分布受下橄榄核内GABA和谷氨酸释放的调节，这可能是通过控制橄榄核神经元之间电紧张性耦合的效能来实现的。通过在橄榄核内注射含有GABA(A)（印防己毒素）和/或AMPA [1,2,3,4-四氢-6-硝基-2,3-二氧代-苯并[f]喹喔啉-7-磺酰胺二钠（NBQX）]受体拮抗剂的溶液，同时进行多个电极记录自发的小腿2a复合峰活动，比较了这两种神经递质在调节同步模式方面的相对强度。注射任何一种拮抗剂都会导致位于同一矢状旁向、宽度约为250微米的皮质条带内的细胞之间同步性增加。印防己毒素还增加了位于不同皮质条带内细胞之间的复合峰同步性，导致条带模式不那么明显，而注射NBQX则倾向于降低此类细胞之间的复合峰同步性，增强条带模式。通过先单独注射一种拮抗剂，然后再与另一种拮抗剂联合注射，评估了这两类橄榄核传入纤维的相对强度。单独注射NBQX后增强的复合峰同步条带模式在随后两种拮抗剂联合注射期间仍然存在。此外，单独注射印防己毒素后复合峰活动的广泛同步在印防己毒素和NBQX联合注射后部分或完全逆转。橄榄核内注射引起的攀爬纤维反射变化与自发复合峰活动观察到的变化相似，表明印防己毒素和NBQX对同步分布的影响反映了下橄榄核神经元有效耦合模式的变化，并证明同步复合峰活动不需要同时对橄榄核细胞进行兴奋性输入。最后，研究了运动皮质刺激期间的同步模式。发现运动皮质诱发的复合峰活动的同步模式与自发活动的同步模式相似，表明电紧张性耦合在确定橄榄小脑系统对传入输入的反应中起重要作用。此外，橄榄核内注射印防己毒素增加了诱发反应的空间分布。总之，这些结果为以下假设提供了证据：下橄榄核神经元通过缝隙连接的电紧张性耦合是复合峰同步的基础机制，并且这种耦合在确定橄榄小脑系统对突触输入的反应中起重要作用。
