Gallo Research Center, Emeryville, California 94608, USA.
J Neurosci. 2010 Oct 27;30(43):14502-12. doi: 10.1523/JNEUROSCI.3909-10.2010.
Spontaneous firing of ventral tegmental area (VTA) dopamine (DA) neurons provides ambient levels of DA in target areas such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC). Here we report that the glial cell line-derived neurotrophic factor (GDNF), produced in one target region, the NAc, is retrogradely transported by DA neurons to the VTA where the growth factor positively regulates the spontaneous firing activity of both NAc- and PFC-projecting DA neurons in a mechanism that requires the activation of the mitogen-activated protein kinase (MAPK) pathway. We also show that the consequence of GDNF-mediated activation of the MAPK signaling cascade in the VTA is an increase in DA overflow in the NAc. Together, these results demonstrate that NAc-produced GDNF serves as a retrograde enhancer that upregulates the activity of the mesocorticolimbic DA system.
腹侧被盖区 (VTA) 多巴胺 (DA) 神经元的自发放电为靶区（如伏隔核 (NAc) 和前额叶皮层 (PFC)）提供了环境水平的 DA。在这里，我们报告说，胶质细胞系源性神经营养因子 (GDNF) 在一个靶区（NAc）中产生，通过 DA 神经元逆行运输到 VTA，在那里生长因子通过需要激活丝裂原活化蛋白激酶 (MAPK) 途径来正向调节 NAc 和 PFC 投射 DA 神经元的自发放电活动。我们还表明，GDNF 介导的 MAPK 信号级联在 VTA 中的激活的后果是 NAc 中 DA 溢出的增加。总之，这些结果表明，NAc 产生的 GDNF 作为一种逆行增强剂，上调了中边缘多巴胺系统的活性。
