Daun Silvia, Rubin Jonathan E, Rybak Ilya A
Department of Mathematics, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Comput Neurosci. 2009 Aug;27(1):3-36. doi: 10.1007/s10827-008-0124-4. Epub 2009 Jan 6.
Central pattern generators (CPGs) consisting of interacting groups of neurons drive a variety of repetitive, rhythmic behaviors in invertebrates and vertebrates, such as arise in locomotion, respiration, mastication, scratching, and so on. These CPGs are able to generate rhythmic activity in the absence of afferent feedback or rhythmic inputs. However, functionally relevant CPGs must adaptively respond to changing demands, manifested as changes in oscillation period or in relative phase durations in response to variations in non-patterned inputs or drives. Although many half-center CPG models, composed of symmetric units linked by reciprocal inhibition yet varying in their intrinsic cellular properties, have been proposed, the precise oscillatory mechanisms operating in most biological CPGs remain unknown. Using numerical simulations and phase-plane analysis, we comparatively investigated how the intrinsic cellular features incorporated in different CPG models, such as subthreshold activation based on a slowly inactivating persistent sodium current, adaptation based on slowly activating calcium-dependent potassium current, or post-inhibitory rebound excitation, can contribute to the control of oscillation period and phase durations in response to changes in excitatory external drive to one or both half-centers. Our analysis shows that both the sensitivity of oscillation period to alterations of excitatory drive and the degree to which the duration of each phase can be separately controlled depend strongly on the intrinsic cellular mechanisms involved in rhythm generation and phase transitions. In particular, the CPG formed from units incorporating a slowly inactivating persistent sodium current shows the greatest range of oscillation periods and the greatest degree of independence in phase duration control by asymmetric inputs. These results are explained based on geometric analysis of the phase plane structures corresponding to the dynamics for each CPG type, which in particular helps pinpoint the roles of escape and release from synaptic inhibition in the effects we find.
由相互作用的神经元群组成的中枢模式发生器（CPG）驱动无脊椎动物和脊椎动物的各种重复性节律行为，如运动、呼吸、咀嚼、抓挠等过程中出现的行为。这些CPG能够在没有传入反馈或节律性输入的情况下产生节律性活动。然而，功能相关的CPG必须能适应不断变化的需求，表现为振荡周期或相对相位持续时间的变化，以响应非模式化输入或驱动的变化。尽管已经提出了许多半中枢CPG模型，这些模型由通过相互抑制连接的对称单元组成，但它们的内在细胞特性各不相同，大多数生物CPG中精确的振荡机制仍然未知。我们通过数值模拟和相平面分析，比较研究了不同CPG模型中包含的内在细胞特征，如基于缓慢失活的持续性钠电流的阈下激活、基于缓慢激活的钙依赖性钾电流的适应性或抑制后反弹兴奋，如何有助于控制振荡周期和相位持续时间，以响应一个或两个半中枢兴奋性外部驱动的变化。我们的分析表明，振荡周期对兴奋性驱动变化的敏感性以及每个相位持续时间可以被单独控制的程度，在很大程度上取决于节律产生和相位转换所涉及的内在细胞机制。特别是，由包含缓慢失活的持续性钠电流的单元形成的CPG显示出最大的振荡周期范围以及在由不对称输入控制相位持续时间方面的最大独立性。基于对与每种CPG类型动力学相对应的相平面结构的几何分析来解释这些结果，这尤其有助于确定我们所发现的效应中突触抑制的逃逸和释放的作用。
