Activation of group I metabotropic glutamate receptors modulates locomotor-related motoneuron output in mice
Activation of group I metabotropic glutamate receptors modulates locomotor-related motoneuron output in mice
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DOI：
10.1152/jn.01037.2010
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发表时间：
2011-05-01
影响因子：
2.5
通讯作者：
Miles, Gareth B.
中科院分区：
文献类型：
--
作者：
Iwagaki, Noboru;Miles, Gareth B.
Iwagaki N，Miles GB.第一组代谢型谷氨酸受体的激活调节小鼠运动相关运动神经元的输出。J Neurophysiol 105：2108-2120，2011.首次发表于2011年2月23日; doi：10.1152/jn.01037.2010.-通过离子型受体的快速神经递质传递对于通过脊髓运动网络产生运动是至关重要的。此外，谷氨酸可以通过代谢型谷氨酸受体（mGluRs）发挥作用，以调节正在进行的运动活动的时间。在本研究中，我们调查是否mGluRs也调制脊髓运动网络产生的运动输出的强度。应用I组mGluR激动剂（S）-3，5-二羟基苯甘氨酸（DHPG）降低了从离体小鼠脊髓制备物的腰腹根记录的运动相关运动神经元输出的振幅并增加了其频率。脊髓运动神经元的全细胞膜片钳记录揭示了多种机制，其中组I mGluRs调节运动神经元的输出。尽管DHPG使静息膜电位去极化并降低动作电位产生的电压阈值，但I组mGluRs的激活对运动神经元输出具有净抑制作用，这似乎反映了快速失活Na（+）电流和动作电位参数的调制。此外，I组mGluR激活降低运动相关的兴奋性输入运动神经元的幅度。微型兴奋性突触后电流的分析表明，mGluRs通过突触前和突触后机制调节对运动神经元的突触驱动。这些数据突出了I组mGluRs作为脊髓内神经调节的潜在重要来源，除了调节用于运动的中枢模式发生器的组分之外，还可以调节运动行为期间运动神经元输出的强度。鉴于I组mGluR激活降低运动神经元兴奋性，mGluR可提供运动神经元输出的负反馈控制，特别是在高水平的谷氨酸能刺激期间。
Iwagaki N, Miles GB. Activation of group I metabotropic glutamate receptors modulates locomotor-related motoneuron output in mice. J Neurophysiol 105: 2108-2120, 2011. First published February 23, 2011; doi:10.1152/jn.01037.2010.-Fast glutamatergic transmission via ionotropic receptors is critical for the generation of locomotion by spinal motor networks. In addition, glutamate can act via metabotropic glutamate receptors (mGluRs) to modulate the timing of ongoing locomotor activity. In the present study, we investigated whether mGluRs also modulate the intensity of motor output generated by spinal motor networks. Application of the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) reduced the amplitude and increased the frequency of locomotor-related motoneuron output recorded from the lumbar ventral roots of isolated mouse spinal cord preparations. Whole cell patch-clamp recordings of spinal motoneurons revealed multiple mechanisms by which group I mGluRs modulate motoneuron output. Although DHPG depolarized the resting membrane potential and reduced the voltage threshold for action potential generation, the activation of group I mGluRs had a net inhibitory effect on motoneuron output that appeared to reflect the modulation of fast, inactivating Na(+) currents and action potential parameters. In addition, group I mGluR activation decreased the amplitude of locomotor-related excitatory input to motoneurons. Analyses of miniature excitatory postsynaptic currents indicated that mGluRs modulate synaptic drive to motoneurons via both pre- and postsynaptic mechanisms. These data highlight group I mGluRs as a potentially important source of neuromodulation within the spinal cord that, in addition to modulating components of the central pattern generator for locomotion, can modulate the intensity of motoneuron output during motor behavior. Given that group I mGluR activation reduces motoneuron excitability, mGluRs may provide negative feedback control of motoneuron output, particularly during high levels of glutamatergic stimulation.