Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system.
Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system.
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DOI：
10.1523/jneurosci.3909-10.2010
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发表时间：
2010-10-27
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影响因子：
--
通讯作者：
Ron D
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作者：
Wang J;Carnicella S;Ahmadiantehrani S;He DY;Barak S;Kharazia V;Ben Hamida S;Zapata A;Shippenberg TS;Ron D
腹侧被盖区（VTA）多巴胺（DA）神经元的自发放电在靶区域（如丘脑核（NAc）和前额叶皮层（PFC））提供周围水平的DA。在这里，我们报告的胶质细胞源性神经营养因子（GDNF），产生于一个目标区域，NAc，是逆行运输的DA神经元的腹侧被盖区的生长因子积极调节自发放电活动的NAc和PFC投射DA神经元的机制，需要激活的丝裂原活化蛋白激酶（MAPK）途径。我们进一步表明，GDNF介导的VTA中MAPK信号级联激活的结果是NAc中DA溢出的增加。总之，这些结果表明，NA产生的GDNF作为一个逆行增强剂，上调中皮质边缘DA系统的活性。
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 regulate 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 further 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 NA-produced GDNF serves as a retrograde enhancer that upregulates the activity of the mesocorticolimbic DA system.