Nucleus accumbens-derived glial cell line-derived neurotrophic factor is a retrograde enhancer of dopaminergic tone in the mesocorticolimbic system.
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.
Wang
Jun
J
Gallo Research Center, Emeryville, California 94608, USA.
Carnicella
Sebastien
S
Ahmadiantehrani
Somayeh
S
He
Dao-Yao
DY
Barak
Segev
S
Kharazia
Viktor
V
Ben Hamida
Sami
S
Zapata
Agustin
A
Shippenberg
Toni S
TS
Ron
Dorit
D
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000502:physiology*; D003001:Cloning, Molecular; D004298:Dopamine / Q000502:physiology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008032:Limbic System / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000502:physiology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013563:Sympathectomy, Chemical; D017557:Ventral Tegmental Area / Q000378:metabolism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D012313:RNA; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine