Quasiperiodic rhythms of the inferior olive

Inferior olivary activity causes both short-term and long-term changes in cerebellar output underlying motor performance and motor learning. Many of its neurons engage in coherent subthreshold oscillations and are extensively coupled via gap junctions. Studies in reduced preparations suggest that these properties promote rhythmic, synchronized output. However, the interaction of these properties with torrential synaptic inputs in awake behaving animals is not well understood. Here we combine electrophysiological recordings in awake mice with a realistic tissue-scale computational model of the inferior olive to study the relative impact of intrinsic and extrinsic mechanisms governing its activity. Our data and model suggest that if subthreshold oscillations are present in the awake state, the period of these oscillations will be transient and variable. Accordingly, by using different temporal patterns of sensory stimulation, we found that complex spike rhythmicity was readily evoked but limited to short intervals of no more than a few hundred milliseconds and that the periodicity of this rhythmic activity was not fixed but dynamically related to the synaptic input to the inferior olive as well as to motor output. In contrast, in the long-term, the average olivary spiking activity was not affected by the strength and duration of the sensory stimulation, while the level of gap junctional coupling determined the stiffness of the rhythmic activity in the olivary network during its dynamic response to sensory modulation. Thus, interactions between intrinsic properties and extrinsic inputs can explain the variations of spiking activity of olivary neurons, providing a temporal framework for the creation of both the short-term and long-term changes in cerebellar output.

下橄榄核（inferior olive）的活动可引发小脑输出的短时程与长时程变化，而此类变化是运动表现与运动学习的基础。该核团的众多神经元会产生相干性阈下振荡（subthreshold oscillations），并通过缝隙连接（gap junctions）实现广泛的细胞间耦联。针对简化制备标本的相关研究表明，这些特性可促成节律性、同步化的核团输出。然而，在清醒活动的动物体内，这些内在特性与洪流般的突触输入之间的相互作用机制仍未得到充分阐明。本研究结合清醒小鼠的电生理记录（electrophysiological recordings）与下橄榄核的组织尺度计算模型（tissue-scale computational model），探究调控其活动的内在与外在机制的相对影响。我们的实验数据与模型结果均显示，若清醒状态下存在阈下振荡，其振荡周期将呈现瞬时性与可变性。据此，通过采用不同时间模式的感觉刺激，我们可便捷地诱发复杂锋电位（complex spike）的节律性活动，但此类节律活动仅能维持不超过数百毫秒的短时段；且该节律活动的周期并非固定不变，而是动态关联于下橄榄核接收的突触输入以及运动输出。与之相对，从长时程维度来看，下橄榄核的平均锋电位活动不受感觉刺激的强度与时长影响；而缝隙连接耦合（gap junctional coupling）水平则决定了橄榄核网络在响应感觉调制的动态过程中，节律活动的刚性程度。综上，内在特性与外在输入之间的相互作用可解释橄榄核神经元锋电位活动的变异，为小脑输出的短时程与长时程变化提供了时序框架。