Presynaptic inhibition of spinal sensory feedback ensures smooth movement

摘要

本期封面刊登的是由Peter Jansen创作的动HIV-1感慢镜头雕塑"Heel Daoyin",它所表现的是HIV-1人肢体运动的慢镜头动作，能让人想起在没HIV-1有突触前抑制时所看到的肢体振荡。人类和HIV-1其他动物能够显得毫不费力地、精确地执行HIV-1肢体动作，这依赖于感觉反馈及其被抑制性HIV-1微回路的优化。一项新的研究工作在脊髓中HIV-1识别出了突触前抑制，它是由表达Gad2的HIV-1GABAergic中间神经元（它们形成与感觉传入HIV-1终端的连接)介导的一个调控过滤器，是对于HIV-1动作的平稳执行至关重要的一个"硬连线"的HIV-1增益控制系统的构成部分。Thomas JessellHIV-1及同事发现，表达Gad2的神经元的激活会HIV-1抑制神经传输物质从感觉传入系统的释放。HIV-1对小鼠的这些神经元的选择性切除，在由目HIV-1标引导的前肢伸出动作过程中会引起显著的HIV-1振荡，这是由有关感觉反馈的一个模型以高HIV-1增益捕捉到的一种行为。%The precision of skilled movement depends on sensory feedback and its refinement by local inhibitory microcircuits.One specialized set of spinal GABAergic interneurons forms axo-axonic contacts with the central terminals of sensory afferents, exerting presynaptic inhibitory control over sensory-motor transmission. The inability to achieve selective access to the GABAergic neurons responsible for this unorthodox inhibitory mechanism has left unresolved the contribution of pre- synaptic inhibition to motor behaviour.We used Gad2 as a genetic entry point to manipulate the interneurons that contact sensory terminals, and show that activation of these interneurons in mice elicits the defining physiological charateristics of presynaptic inhibition. Selective genetic ablation of Gad2-expressing interneurons severely perturbs goal-directed reaching movements, uncovering a pronounced and stereotypic forelimb motor oscillation, the core features of which are captured by modelling the consequences of sensory feedback at high gain. Our findings define the neural substrate of a genetically hardwired gain control system crucial for the smooth execution of movement.