Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Asahimachidori 1-757, Chuo-ku, Niigata-city, 951-8510, Japan.
Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachidori 1-757, Chuo-ku, Niigata-city, 951-8510, Japan.
Neuroscience. 2019 Jun 1;408:161-176. doi: 10.1016/j.neuroscience.2019.03.026. Epub 2019 Apr 13.
Noradrenaline (NA) modulates the spinal motor networks for locomotion and facilitates neuroplasticity, possibly assisting neuronal network activation and neuroplasticity in the recovery phase of spinal cord injuries. However, neither the effects nor the mechanisms of NA on synaptic transmission and neuronal excitability in spinal ventral horn (VH) neurons are well characterized, especially in rats aged 7 postnatal days or older. To gain insight into NA regulation of VH neuronal activity, we used a whole-cell patch-clamp approach in late neonatal rats (postnatal day 7-15). In voltage-clamp recordings at -70 mV, NA increased the frequency and amplitude of excitatory postsynaptic currents via the activation of somatic α- and β-adrenoceptors of presynaptic neurons. Moreover, NA induced an inward current through the activation of postsynapticα- and β-adrenoceptors. At a holding potential of 0 mV, NA also increased frequency and amplitude of both GABAergic and glycinergic inhibitory postsynaptic currents via the activation of somatic adrenoceptors in presynaptic neurons. In current-clamp recordings, NA depolarized resting membrane potentials and increased the firing frequency of action potentials in VH neurons, indicating that it enhances the excitability of these neurons. Our findings provide new insights that establish NA-based pharmacological therapy as an effective method to activate neuronal networks of the spinal VH in the recovery phase of spinal cord injuries.
去甲肾上腺素（NA）调节脊髓运动网络以促进神经可塑性，可能有助于脊髓损伤恢复阶段神经元网络的激活和神经可塑性。然而，NA 对脊髓腹角（VH）神经元突触传递和神经元兴奋性的影响和机制尚未得到很好的描述，尤其是在出生后 7 天或以上的大鼠中。为了深入了解 NA 对 VH 神经元活动的调节作用，我们在新生后期大鼠（出生后第 7-15 天）中使用全细胞膜片钳技术。在-70 mV 的电压钳记录中，NA 通过激活突触前神经元的体α-和β-肾上腺素能受体，增加兴奋性突触后电流的频率和幅度。此外，NA 通过激活突触后α-和β-肾上腺素能受体诱导内向电流。在 0 mV 的保持电位下，NA 通过激活突触前神经元的体肾上腺素能受体，也增加 GABA 能和甘氨酸能抑制性突触后电流的频率和幅度。在电流钳记录中，NA 使静息膜电位去极化，并增加 VH 神经元动作电位的发放频率，表明它增强了这些神经元的兴奋性。我们的发现提供了新的见解，确立了基于 NA 的药物治疗作为一种有效方法，可在脊髓损伤的恢复阶段激活脊髓 VH 中的神经元网络。
