Van Der Giessen Ruben S, Koekkoek Sebastiaan K, van Dorp Stijn, De Gruijl Jornt R, Cupido Alexander, Khosrovani Sara, Dortland Bjorn, Wellershaus Kerstin, Degen Joachim, Deuchars Jim, Fuchs Elke C, Monyer Hannah, Willecke Klaus, De Jeu Marcel T G, De Zeeuw Chris I
Department of Neuroscience, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
Neuron. 2008 May 22;58(4):599-612. doi: 10.1016/j.neuron.2008.03.016.
The level of electrotonic coupling in the inferior olive is extremely high, but its functional role in cerebellar motor control remains elusive. Here, we subjected mice that lack olivary coupling to paradigms that require learning-dependent timing. Cx36-deficient mice showed impaired timing of both locomotion and eye-blink responses that were conditioned to a tone. The latencies of their olivary spike activities in response to the unconditioned stimulus were significantly more variable than those in wild-types. Whole-cell recordings of olivary neurons in vivo showed that these differences in spike timing result at least in part from altered interactions with their subthreshold oscillations. These results, combined with analyses of olivary activities in computer simulations at both the cellular and systems level, suggest that electrotonic coupling among olivary neurons by gap junctions is essential for proper timing of their action potentials and thereby for learning-dependent timing in cerebellar motor control.
下橄榄核中的电紧张耦联水平极高，但其在小脑运动控制中的功能作用仍不清楚。在这里，我们让缺乏橄榄核耦联的小鼠接受需要依赖学习的定时范式测试。Cx36基因缺陷型小鼠在与音调相关的运动和眨眼反应定时方面均表现受损。它们对非条件刺激的橄榄核峰电位活动潜伏期比野生型小鼠的潜伏期变化显著得多。体内对橄榄核神经元的全细胞记录表明，峰电位定时的这些差异至少部分源于与阈下振荡相互作用的改变。这些结果，结合在细胞和系统水平的计算机模拟中对橄榄核活动的分析，表明间隙连接介导的橄榄核神经元之间的电紧张耦联对于其动作电位的正确定时至关重要，从而对于小脑运动控制中依赖学习的定时也至关重要。
