Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA.
Neuron. 2019 Apr 17;102(2):420-434.e8. doi: 10.1016/j.neuron.2019.02.002. Epub 2019 Feb 27.
Presynaptic inhibition (PSI) of primary sensory neurons is implicated in controlling gain and acuity in sensory systems. Here, we define circuit mechanisms and functions of PSI of cutaneous somatosensory neuron inputs to the spinal cord. We observed that PSI can be evoked by different sensory neuron populations and mediated through at least two distinct dorsal horn circuit mechanisms. Low-threshold cutaneous afferents evoke a GABA-receptor-dependent form of PSI that inhibits similar afferent subtypes, whereas small-diameter afferents predominantly evoke an NMDA-receptor-dependent form of PSI that inhibits large-diameter fibers. Behaviorally, loss of either GABA receptors (GABARs) or NMDA receptors (NMDARs) in primary afferents leads to tactile hypersensitivity across skin types, and loss of GABARs, but not NMDARs, leads to impaired texture discrimination. Post-weaning age loss of either GABARs or NMDARs in somatosensory neurons causes systemic behavioral abnormalities, revealing critical roles of two distinct modes of PSI of somatosensory afferents in adolescence and throughout adulthood.
前突触抑制（PSI）在初级感觉神经元中被牵涉到在感觉系统中控制增益和锐度。在这里，我们定义了皮肤感觉神经元输入到脊髓的 PSI 的电路机制和功能。我们观察到，PSI 可以由不同的感觉神经元群体引发，并通过至少两种不同的背角电路机制来介导。低阈值皮肤传入纤维诱发 GABA 受体依赖性的 PSI，抑制相似的传入纤维亚型，而小直径传入纤维主要诱发 NMDA 受体依赖性的 PSI，抑制大直径纤维。在行为上，初级传入纤维中 GABA 受体（GABARs）或 NMDA 受体（NMDARs）的缺失会导致各种皮肤类型的触觉过敏，而 GABARs 的缺失，而不是 NMDARs 的缺失，会导致纹理辨别受损。感觉神经元中 GABARs 或 NMDARs 的发育后缺失会导致全身性行为异常，这揭示了两种不同模式的 PSI 在青春期和整个成年期对感觉传入的关键作用。
