Mechanisms and functional impact of Group I metabotropic glutamate receptor modulation of excitability in mouse MNTB neurons
Mechanisms and functional impact of Group I metabotropic glutamate receptor modulation of excitability in mouse MNTB neurons
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DOI：
10.1002/syn.22137
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发表时间：
2019-10-14
期刊：
影响因子：
2.3
通讯作者：
Kushmerick, Christopher
中科院分区：
文献类型：
--
作者：
dos Santos e Alhadas, Everton;Bernal Correa, Ana Maria;Kushmerick, Christopher
我们研究了I组代谢型谷氨酸受体对小鼠斜方体内侧核（MNTB）神经元兴奋性的影响。选择性激动剂，S-3，5-二羟基苯甘氨酸（DHPG），诱发静息电位的剂量依赖性去极化，增加膜电阻，增加下垂去极化，并促进反弹动作电位放电。在电压钳下，DHPG诱发了一种内向电流，称为I-DHPG，该电流在出生后P56期间发育稳定。I-DHPG在25-34 ℃范围内具有低的温度依赖性，与通道机制一致。然而，I-V关系呈倒U形，在K+或Cl-的计算能斯特电位下不反转。因此，可能多于一种离子类型有助于I-DHPG，并且混合可能是电压依赖性的。I-DHPG对Na+通道阻断剂河豚毒素和阿米洛利以及iGluR抑制剂（CNQX和MK 801）具有抗性。Ba ~（2+）（500 μ M）对I-DHPG的抑制率为21%，ZD 7288（100 μ M）为60%，两种拮抗剂合用时抑制率为73%，表明KIR通道和HCN通道对电流有贡献。I-H的电压钳测量表明DHPG使G（max）小幅增加（6%），而电压依赖性没有变化。DHPG降低动作电位基强度，并减少突触后AP失败的数量在高频刺激的Held的花萼。因此，突触后I组mGlu受体的激活改变了MNTB神经元的兴奋性，并有助于该听觉中继核中高频放电的可靠性。
We examined effects of Group I metabotropic glutamate receptors on the excitability of mouse medial nucleus of the trapezoid body (MNTB) neurons. The selective agonist, S-3,5-dihydroxyphenylglycine (DHPG), evoked a dose-dependent depolarization of the resting potential, increased membrane resistance, increased sag depolarization, and promoted rebound action potential firing. Under voltage-clamp, DHPG evoked an inward current, referred to as I-DHPG, which was developmentally stable through postnatal day P56. I-DHPG had low temperature dependence in the range 25-34 degrees C, consistent with a channel mechanism. However, the I-V relationship took the form of an inverted U that did not reverse at the calculated Nernst potential for K+ or Cl-. Thus, it is likely that more than one ion type contributes to I-DHPG and the mix may be voltage dependent. I-DHPG was resistant to the Na+ channel blockers tetrodotoxin and amiloride, and to inhibitors of iGluR (CNQX and MK801). I-DHPG was inhibited 21% by Ba2+ (500 mu M), 60% by ZD7288 (100 mu M) and 73% when the two antagonists were applied together, suggesting that KIR channels and HCN channels contribute to the current. Voltage clamp measurements of I-H indicated a small (6%) increase in G(max) by DHPG with no change in the voltage dependence. DHPG reduced action potential rheobase and reduced the number of post-synaptic AP failures during high frequency stimulation of the calyx of Held. Thus, activation of post-synaptic Group I mGlu receptors modifies the excitability of MNTB neurons and contributes to the reliability of high frequency firing in this auditory relay nucleus.