Beauchamp James A, Pearcey Gregory E P, Khurram Obaid U, Negro Francesco, Dewald Julius P A, Heckman C J
Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, Chicago, IL, USA.
Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
J Physiol. 2025 Apr;603(8):2443-2463. doi: 10.1113/JP287446. Epub 2025 Mar 28.
Motoneurons are the final common pathway for all motor commands and possess intrinsic electrical properties that must be tuned to control muscle across the full range of motor behaviours. Neuromodulatory input from the brainstem is probably essential for adapting motoneuron properties to match this diversity of motor tasks. A primary mechanism of this adaptation, control of dendritic persistent inward currents (PICs) in motoneurons by brainstem monoaminergic systems, generates both amplification and prolongation of synaptic inputs. While essential, there is an inherent tension between this amplification and prolongation. Although amplification by PICs allows for quick recruitment and acceleration of motoneuron discharge, PICs must be deactivated to derecruit motoneurons upon movement cessation. In contrast, during stabilizing or postural tasks, PIC-induced prolongation of synaptic inputs is critical for sustained motoneuron discharge. Here, we designed two motor tasks that challenged the inhibitory control of PICs, generating unduly PIC prolongation that increases variability in human torque control. This included a paradigm combining a discrete motor task with a stabilizing task and another involving muscle length-induced changes to the balance of excitatory and inhibitory inputs available for controlling PICs. We show that prolongation from PICs introduces difficulties in ankle torque control and that these difficulties are further degraded at shorter muscle lengths when PIC prolongation is greatest. These results highlight the necessity for inhibitory control of PICs and showcase issues introduced when inhibitory control is constrained. Our findings suggest that, like sensory systems, errors are inherent in motor systems. These errors are not due to problems in the perception of movement-related sensory input but are embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) where pathological shifts in monoamines may further amplify these errors. KEY POINTS: All motor commands are processed via spinal motoneurons, whose intrinsic electrical properties are adapted by brainstem neuromodulatory input. The effects of these neuromodulatory inputs (i.e. persistent inward currents; PICs) must be tightly regulated by inhibitory inputs to allow for the large repertoire of human motor behaviours. We designed two motor tasks to restrict the ability of inhibitory synaptic inputs to control PICs and show that this generates substantial errors that reduce the precision of motor output in humans. Our findings suggest that errors are inherent in motor systems and embedded in the final stage of motor output. This has many implications relevant to clinical conditions (e.g. chronic stroke) and may, speculatively, shed light on contributing factors to muscle cramps.
运动神经元是所有运动指令的最终共同通路,具有内在电特性,必须对其进行调节以在整个运动行为范围内控制肌肉。来自脑干的神经调节输入可能对于使运动神经元特性适应这种多样的运动任务至关重要。这种适应的一种主要机制,即脑干单胺能系统对运动神经元中树突状持续内向电流(PICs)的控制,会产生突触输入的放大和延长。虽然这很重要,但这种放大和延长之间存在内在矛盾。尽管PICs的放大允许运动神经元放电的快速募集和加速,但在运动停止时必须使PICs失活以解除运动神经元的募集。相反,在稳定或姿势任务期间,PICs诱导的突触输入延长对于运动神经元的持续放电至关重要。在这里,我们设计了两项运动任务,对PICs的抑制性控制提出挑战,产生过度的PICs延长,从而增加人类扭矩控制的变异性。这包括将离散运动任务与稳定任务相结合的范式,以及另一项涉及肌肉长度引起的用于控制PICs的兴奋性和抑制性输入平衡变化的任务。我们表明,PICs的延长给踝关节扭矩控制带来困难,并且当PICs延长最大时,在较短肌肉长度下这些困难会进一步加剧。这些结果突出了对PICs进行抑制性控制的必要性,并展示了抑制性控制受到限制时所产生的问题。我们的研究结果表明,与感觉系统一样,运动系统中也存在固有误差。这些误差并非由于与运动相关的感觉输入的感知问题,而是嵌入在运动输出的最后阶段。这与临床病症(如慢性中风)有许多关联,在这些病症中,单胺的病理性变化可能会进一步放大这些误差。要点:所有运动指令都通过脊髓运动神经元进行处理,其内在电特性由脑干神经调节输入进行调节。这些神经调节输入(即持续内向电流;PICs)的作用必须通过抑制性输入进行严格调节,以实现人类多样的运动行为。我们设计了两项运动任务来限制抑制性突触输入控制PICs的能力,并表明这会产生大量误差,降低人类运动输出的精度。我们的研究结果表明,误差在运动系统中是固有的,并且嵌入在运动输出的最后阶段。这与临床病症(如慢性中风)有许多关联,并且推测可能有助于揭示肌肉痉挛的促成因素。