RT Journal Article SR Electronic T1 Ventral tegmental area astrocytes orchestrate avoidance and approach behavior JF bioRxiv FD Cold Spring Harbor Laboratory SP 401919 DO 10.1101/401919 A1 J. A. Gomez A1 J. Perkins A1 G. Beaudoin A1 N. Cook A1 S. A. Quraishi A1 Erin Szoeke A1 M. J. Wanat A1 C. A. Paladini YR 2018 UL http://biorxiv.org/content/early/2018/08/27/401919.abstract AB The ventral tegmental area (VTA) is a heterogeneous midbrain structure, containing neurons and astrocytes, that coordinates approach and avoidance behaviors by integrating activity from numerous afferents. Within astrocyte-neuron networks, astrocytes control signals from distinct afferents in a circuit-speci?c manner, but whether this capacity scales up to drive motivated behavior has been undetermined. Using genetic and optical dissection strategies in vitro and during behavior we report that VTA astrocytes tune glutamatergic signaling selectively on local inhibitory neurons to drive a functional circuit for learned avoidance. In this circuit, VTA astrocytes facilitate excitation of local GABA neurons to increase inhibition of dopamine neurons. The increased inhibition of dopamine neurons elicits real-time and learned avoidance behavior that is suf?cient to impede expression of learned preference for reward. Despite the large number of functions performed by astrocytes, loss of one glutamate transporter (GLT-1) from VTA astrocytes selectively blocks these avoidance behaviors and spares preference for reward. Thus, VTA astrocytes selectively regulate excitation of local GABA neurons to drive a distinct learned avoidance circuit that opposes learned approach behavior.