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

Publication date: 20 December 2016
Source:Cell Reports, Volume 17, Issue 12
Author(s): Sarah X. Luo, Leah Timbang, Jae-Ick Kim, Yulei Shang, Kadellyn Sandoval, Amy A. Tang, Jennifer L. Whistler, Jun B. Ding, Eric J. Huang
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.

Graphical abstract

Teaser

Luo et al. show that loss of TGF-β signaling in mature DA neurons leads to defects in axonal and dendritic growth and in the maintenance of balanced excitation-inhibition synaptic input in early postnatal life. Mice lacking TGF-β signaling in DA neurons exhibit hyperactivity and behavioral inflexibility in reversal learning.


http://ift.tt/2iiAKT0