Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China; Department of Physiology, Changzhi Medical College, Changzhi, 046000, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Neurochem Int. 2019 Jan;122:85-93. doi: 10.1016/j.neuint.2018.11.007. Epub 2018 Nov 15.
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.
腹侧被盖区（VTA）和黑质致密部（SNc）中的 GABA 能性穹窿状中脑背侧核（RMTg）与多巴胺能神经元相互连接，并参与单胺能核团的抑制性控制。目前，尚不清楚大鼠 SNc 的单侧 6-羟多巴胺损伤是否会影响 RMTg 中的 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 的损伤增加了 RMTg 中 GABA 能神经元的放电率和谷氨酸水平。RMTg 内注射 AMPA 受体激动剂（S）-AMPA 增加了假手术和损伤大鼠中 GABA 能神经元的放电率，而 AMPA 受体拮抗剂 NBQX 降低了神经元的放电率。此外，RMTg 内注射（S）-AMPA 降低了两组大鼠中内侧前额叶皮质（mPFC）中多巴胺和 5-羟色胺的水平；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，损伤大鼠中（S）-AMPA 和 NBQX 对 RMTg 中 GABA 能神经元放电率和 mPFC 中多巴胺和 5-羟色胺释放的作用时间延长。此外，与假手术大鼠相比，损伤大鼠的 t-GluR1 和 p-GluR1-S831 亚基蛋白表达增加。因此，损伤大鼠中这些变化与 RMTg 中谷氨酸释放增加和 GluR1 亚基组成的 AMPA 受体表达上调有关，这表明黑质纹状体通路的退化增强了 RMTg 中的 AMPA 受体介导的兴奋性传递。
