First Author | Luo SX | Year | 2016 |
Journal | Cell Rep | Volume | 17 |
Issue | 12 | Pages | 3233-3245 |
PubMed ID | 28009292 | Mgi Jnum | J:241889 |
Mgi Id | MGI:5903821 | Doi | 10.1016/j.celrep.2016.11.068 |
Citation | Luo SX, et al. (2016) TGF-beta Signaling in Dopaminergic Neurons Regulates Dendritic Growth, Excitatory-Inhibitory Synaptic Balance, and Reversal Learning. Cell Rep 17(12):3233-3245 |
abstractText | 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 beta (TGF-beta) signaling to promote the growth of axons and dendrites. Surprisingly, removing TGF-beta type II receptor in DA neurons also disrupts the balance in TGF-beta1 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-beta 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-beta 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. |