Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice
Adenosine-mediated modulation of ventral horn interneurons and spinal motoneurons in neonatal mice
复制标题
腺苷介导的新生小鼠腹角中间神经元和脊髓运动神经元的调节
作者：
Emily C. Witts;Filipe Nascimento;G. Miles
神经调节允许神经网络适应不同的环境和生物力学需求。嘌呤能信号是中枢神经系统许多部分的重要调节系统，包括运动控制回路。我们最近已经表明腺苷调节哺乳动物脊髓运动控制电路的输出（Witts EC，Panetta KM，Miles GB. J Neurophysiol 107：1925-1934，2012）。在这里，我们研究了这种腺苷介导的调制的细胞机制。全细胞膜片钳记录腹角中间神经元和运动神经元在体外小鼠脊髓切片制备。我们发现腺苷使中间神经元超极化，并降低对中间神经元的突触输入的频率和幅度。这两种作用都被A1型腺苷受体拮抗剂DPCPX阻断。从中间神经元记录的微型突触后电流的分析表明，腺苷降低其频率，但不振幅，表明腺苷作用于突触前受体，以调节突触传递。与中间神经元相反，运动神经元的记录显示腺苷介导的去极化。腺苷再次降低了运动神经元突触输入的频率和幅度，但我们没有看到对微小的突触后电流的影响。这些对运动神经元的作用也被DPCPX阻断。综上所述，这些结果表明腺苷，通过A1受体，在小鼠脊髓中的作用的差异。腺苷对腹角中间神经元具有一般抑制作用，同时可能维持运动神经元的兴奋性。这可能允许适应由神经元间网络产生的运动模式，同时有助于确保维持整体运动输出。
Neuromodulation allows neural networks to adapt to varying environmental and biomechanical demands. Purinergic signaling is known to be an important modulatory system in many parts of the CNS, including motor control circuitry. We have recently shown that adenosine modulates the output of mammalian spinal locomotor control circuitry (Witts EC, Panetta KM, Miles GB. J Neurophysiol 107: 1925–1934, 2012). Here we investigated the cellular mechanisms underlying this adenosine-mediated modulation. Whole cell patch-clamp recordings were performed on ventral horn interneurons and motoneurons within in vitro mouse spinal cord slice preparations. We found that adenosine hyperpolarized interneurons and reduced the frequency and amplitude of synaptic inputs to interneurons. Both effects were blocked by the A1-type adenosine receptor antagonist DPCPX. Analysis of miniature postsynaptic currents recorded from interneurons revealed that adenosine reduced their frequency but not amplitude, suggesting that adenosine acts on presynaptic receptors to modulate synaptic transmission. In contrast to interneurons, recordings from motoneurons revealed an adenosine-mediated depolarization. The frequency and amplitude of synaptic inputs to motoneurons were again reduced by adenosine, but we saw no effect on miniature postsynaptic currents. Again these effects on motoneurons were blocked by DPCPX. Taken together, these results demonstrate differential effects of adenosine, acting via A1 receptors, in the mouse spinal cord. Adenosine has a general inhibitory action on ventral horn interneurons while potentially maintaining motoneuron excitability. This may allow for adaptation of the locomotor pattern generated by interneuronal networks while helping to ensure the maintenance of overall motor output.
影响因子：
56.9
作者：
Porkka-Heiskanen, T;Strecker, RE;McCarley, RW
通讯作者：
McCarley, RW
影响因子：
6.1
作者：
Rivera-Oliver, Marla;Diaz-Rios, Manuel
通讯作者：
Diaz-Rios, Manuel
影响因子：
2.5
作者：
Iwagaki, Noboru;Miles, Gareth B.
通讯作者：
Miles, Gareth B.