Mahrous Amr A, Liang Lucy, Balaguer Josep-Maria, Ho Jonathan C, Grigsby Erinn M, Karapetyan Vahagn, Damiani Arianna, Fields Daryl P, Gonzalez-Martinez Jorge A, Gerszten Peter C, Bennett David J, Heckman C J, Pirondini Elvira, Capogrosso Marco
Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Rehab Neural Engineering Labs, University of Pittsburgh, Pittsburgh, PA, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA; Center for Neural Basis of Cognition, Pittsburgh, PA, USA.
Cell Rep. 2025 Jan 28;44(1):115100. doi: 10.1016/j.celrep.2024.115100. Epub 2024 Dec 18.
A century of research established that GABA inhibits proprioceptive inputs presynaptically to sculpt spinal neural inputs into skilled motor output. Recent results in mice challenged this theory by showing that GABA can also facilitate action potential conduction in proprioceptive afferents. Here, we tackle this controversy in monkeys, the most human-relevant animal model, and show that GABA receptors (GABARs) indeed facilitate sensory inputs to spinal motoneurons and interneurons and that this mechanism also influences sensory transmission to supraspinal centers. We performed causal manipulations of GABARs with intrathecal pharmacology in anesthetized monkeys while recording electrical signals in the muscles, spinal cord, thalamus, and cortex. We show that blocking GABARs suppresses spinal reflexes to hand muscles, sensory-evoked single-unit firing in the spinal cord, and sensory-evoked potentials in the thalamus and somatosensory cortex. Our results portray a sophisticated picture of presynaptic modulation of sensory inputs by GABA in the spinal cord.
一个世纪的研究证实，γ-氨基丁酸（GABA）在突触前抑制本体感觉输入，从而将脊髓神经输入塑造为熟练的运动输出。最近在小鼠身上的研究结果对这一理论提出了挑战，研究表明GABA还可以促进本体感觉传入纤维的动作电位传导。在此，我们在与人类关系最为密切的动物模型——猴子身上解决了这一争议，并表明GABA受体（GABARs）确实促进了脊髓运动神经元和中间神经元的感觉输入，而且这一机制也影响了向脊髓上中枢的感觉传递。我们在麻醉的猴子身上通过鞘内药理学对GABARs进行了因果操纵，同时记录肌肉、脊髓、丘脑和皮层中的电信号。我们表明，阻断GABARs会抑制手部肌肉的脊髓反射、脊髓中感觉诱发的单单位放电以及丘脑和体感皮层中的感觉诱发电位。我们的研究结果描绘了一幅脊髓中GABA对感觉输入进行突触前调制的复杂图景。
