Reduction of metabotropic glutamate receptor-mediated heterosynaptic inhibition of developing MNTB-LSO inhibitory synapses
Reduction of metabotropic glutamate receptor-mediated heterosynaptic inhibition of developing MNTB-LSO inhibitory synapses
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DOI：
10.1111/j.1460-9568.2007.05656.x
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发表时间：
2007-07-01
影响因子：
3.4
通讯作者：
Nabekura, Junichi
中科院分区：
文献类型：
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作者：
Nishimaki, Takuya;Jang, Il-Sung;Nabekura, Junichi
外侧上橄榄核(LSO)是脑干内的一个听觉传递中枢，通过整合对侧耳经斜方体内侧核(MNTB)的GABA/甘氨酸能输入和同侧耳经耳蜗腹核(VCN)的谷氨酸能输入，编码耳间水平差异以进行声音定位。用全细胞膜片钳技术研究了VCN终末释放的谷氨酸和MNTB抑制终末表达的代谢型谷氨酸受体(MGluR)介导的异突触调制作用。在出生后第4-8天(P4-8)，重复刺激VCN-LSO兴奋性传入可显著抑制MNTB-LSO抑制性突触后电流(IPSCs)的幅度，使其变异系数增大，并改变成对脉冲比率。MGluR2/3拮抗剂LY341495可拮抗上述作用。因此，重复刺激VCN-LSO谷氨酸能传入对MNTB-LSO突触反应的抑制可能是由于MNTB-LSO突触前终末存在mGluR2/3的激活所致。MGluR2/3激动剂DCG IV对MNTB-LSO IPSCs的抑制率随发育而降低，至出生后第3周基本消失。LSO中mGluR2/3免疫组织化学染色在P18时也较P4时明显减弱。我们认为，mGluR介导的MNTB-LSO GABA能/甘氨酸能传递的异突触调节可能有助于成人听觉回路的发育。
The lateral superior olivary nucleus (LSO) is an auditory relay centre within the brain stem that encodes interaural level differences for sound localization by integrating GABA/glycinergic input from the contralateral ear via the medial nucleus of the trapezoid body (MNTB), and glutamatergic input from the ipsilateral ear via the ventral cochlear nucleus (VCN). To study the development of the circuits that contribute to the establishment of sound localization, the heterosynaptic modulation mediated by glutamate released from VCN terminals and group II metabotropic glutamate receptor (mGluR) expressed on MNTB inhibitory terminals was investigated using whole-cell patch-clamp techniques. At postnatal day-4-8 (P4-8), repetitive stimulation of the VCN-LSO excitatory afferents caused significant inhibition of MNTB-LSO inhibitory postsynaptic currents (IPSCs) in amplitude with an increase of its coefficient of variation and changed the paired-pulse ratio. These effects were antagonized by LY341495, an mGluR2/3 antagonist. Thus, the suppression of MNTB-LSO synaptic responses induced by repetitive stimulation applied to the VCN-LSO glutamatergic afferent is presumably due to an activation of mGluR2/3 existing on MNTB-LSO presynaptic terminals. The suppression rate of MNTB-LSO IPSCs by DCG IV, an mGluR2/3 agonist, decreased with development and became negligible by the third week after birth. The immunohistochemical staining of mGluR2/3 in the LSO was also less apparent at P18 compared with that at P4. We suggest that mGluR-mediated heterosynaptic modulation of MNTB-LSO GABAergic/glycinergic transmission might contribute to the development of appropriate adult auditory circuits.