TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning

Sarah X. Luo, Leah Timbang, Jae Ick Kim, Yulei Shang, Kadellyn Sandoval, Amy A. Tang, Jennifer Whistler, Jun B. Ding, Eric J. Huang

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Neural circuits involving midbrain dopaminergic (DA) neurons regulate reward and goal-directed behaviors. Although local GABAergic input is known to modulate DA circuits, the mechanism that controls excitatory/inhibitory synaptic balance in DA neurons remains unclear. Here, we show that DA neurons use autocrine transforming growth factor β (TGF-β) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-β type II receptor in DA neurons also disrupts the balance in TGF-β1 expression in DA neurons and neighboring GABAergic neurons, which increases inhibitory input, reduces excitatory synaptic input, and alters phasic firing patterns in DA neurons. Mice lacking TGF-β signaling in DA neurons are hyperactive and exhibit inflexibility in relinquishing learned behaviors and re-establishing new stimulus-reward associations. These results support a role for TGF-β in regulating the delicate balance of excitatory/inhibitory synaptic input in local microcircuits involving DA and GABAergic neurons and its potential contributions to neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)3233-3245
Number of pages13
JournalCell Reports
Volume17
Issue number12
DOIs
StatePublished - Dec 20 2016
Externally publishedYes

Keywords

  • axon
  • dendrite
  • dopaminergic neurons
  • inhibitory synapse
  • phasic firing
  • reversal learning
  • TGF-β

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Luo, S. X., Timbang, L., Kim, J. I., Shang, Y., Sandoval, K., Tang, A. A., Whistler, J., Ding, J. B., & Huang, E. J. (2016). TGF-β Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning. Cell Reports, 17(12), 3233-3245. https://doi.org/10.1016/j.celrep.2016.11.068