Long Michael A, Deans Michael R, Paul David L, Connors Barry W
Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.
J Neurosci. 2002 Dec 15;22(24):10898-905. doi: 10.1523/JNEUROSCI.22-24-10898.2002.
Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at approximately 5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a beta-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.
下橄榄核（IO）的神经元形成攀缘纤维，可兴奋小脑皮质的浦肯野细胞。IO神经元通过缝隙连接进行电耦合，它们在膜电位上产生频率约为5 - 10Hz的同步亚阈值振荡。实验和理论研究表明，IO神经元的节律性和同步性都需要电耦合。我们在体外小鼠脑干切片中记录了成对的IO神经元。野生型（WT）小鼠的大多数神经元对是电耦合的，但对于神经元缝隙连接蛋白连接蛋白36基因敲除（KO）小鼠的神经元之间，耦合很少且较弱。WT和KO小鼠的IO细胞都产生了频率和幅度相似的节律性膜波动。WT神经元相邻对之间的振荡强烈同步，而KO对的振荡则不相关。KO神经元中的自发振荡不受河豚毒素的阻断。WT和KO小鼠的自发振荡神经元都偶尔产生与其膜节律同步的动作电位，但只有WT神经元对的动作电位是同步的。将一种被认为通过促进IO中的节律发生来诱发震颤的β-咔啉衍生物哈尔满全身注射到WT和KO小鼠体内。哈尔满诱发的震颤在两种基因型中都很强烈且难以区分，这表明缝隙连接介导的同步性在哈尔满诱发的震颤中不起作用。我们得出结论，电耦合对于单个IO神经元产生自发亚阈值振荡不是必需的，但耦合可以使IO神经元之间的节律性活动同步。
