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Enhanced AMPA receptor-mediated excitatory transmission in the rodent rostromedial tegmental nucleus following lesion of the nigrostriatal pathway.
Neurochemistry international ( IF 4.2 ) Pub Date : 2018-11-15 , DOI: 10.1016/j.neuint.2018.11.007
Yongli Chang 1 , Chengxue Du 2 , Lingna Han 3 , Shuxuan Lv 2 , Jin Zhang 2 , Guanyun Bian 4 , Guoyi Tang 2 , Yiwei Liu 2 , Tao Chen 2 , Jian Liu 2
Affiliation  

The GABAergic rostromedial tegmental nucleus (RMTg) has reciprocal connections with the dopaminergic ventral tegmental area and substantia nigra pars compacta (SNc), and is involved in inhibitory control of monoaminergic nuclei. At present, it is not clear whether unilateral 6-hydroxydopamine lesions of the SNc in rats affect AMPA receptor-mediated excitatory transmission in the RMTg. Here we found that lesions of the SNc in rats increased the firing rate of GABAergic neurons and the level of glutamate in the RMTg compared to sham-operated rats. Intra-RMTg injection of AMPA receptor agonist (S)-AMPA increased the firing rate of the GABAergic neurons in both sham-operated and the lesioned rats, while AMPA receptor antagonist NBQX decreased the firing rate of the neurons. Further, intra-RMTg injection of (S)-AMPA decreased the levels of dopamine and serotonin in the medial prefrontal cortex (mPFC) in the two groups of rats; conversely, NBQX increased the levels of dopamine and serotonin. Compared to sham-operated rats, the duration of (S)-AMPA and NBQX action on the firing rate of GABAergic neurons in the RMTg and release of doapmine and serotonin in the mPFC was prolonged in the lesioned rats. In addition, lesions of the SNc in rats increased protein expression of t-GluR1 and p-GluR1-S831 subunits compared to sham-operated rats. Therefore, these changes in the lesioned rats are associated with increased release of glutamate and up-regulated expression of GluR1 subunit-containing AMPA receptors in the RMTg, which suggest that degeneration of the nigrostriatal pathway enhances AMPA receptor-mediated excitatory transmission in the RMTg.

中文翻译:

纹状体黑质纹状体病变后,啮齿类动物的罗纹被膜核中AMPA受体介导的兴奋性传递增强。

GABA能级星形胶质被盖核(RMTg)与多巴胺能腹盖区和黑质致密部(SNc)相互连接,并参与单胺能核的抑制性控制。目前,尚不清楚大鼠SNc的单侧6-羟基多巴胺损伤是否影响RMTg中AMPA受体介导的兴奋性传递。在这里,我们发现,与假手术大鼠相比,大鼠SNc损伤增加了GABA能神经元的放电速度和RMTg中的谷氨酸水平。RMTg内注射AMPA受体激动剂(S)-AMPA可以增加假手术和病变大鼠的GABA能神经元的放电率,而AMPA受体拮抗剂NBQX则可以降低神经元的放电率。进一步,RMTg内注射(S)-AMPA可降低两组大鼠内侧前额叶皮层(mPFC)中的多巴胺和血清素水平;相反,NBQX增加了多巴胺和5-羟色胺的水平。与假手术大鼠相比,病变大鼠的(S)-AMPA和NBQX作用对RMTg中GABA能神经元放电速率和mPFC中多巴胺和5-羟色胺释放的作用持续时间延长。此外,与假手术大鼠相比,大鼠SNc损伤增加了t-GluR1和p-GluR1-S831亚基的蛋白表达。因此,病变大鼠的这些变化与RMTg中谷氨酸盐的释放增加和含GluR1亚基的AMPA受体的表达上调有关,
更新日期:2018-11-15
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