PT  - JOURNAL ARTICLE
AU  - Rafael Renteria
AU  - Christian Cazares
AU  - Emily T. Baltz
AU  - Drew C. Schreiner
AU  - Ege A. Yalcinbas
AU  - Thomas Steinkellner
AU  - Thomas S. Hnasko
AU  - Christina M. Gremel
TI  - Mechanism for differential recruitment of orbitostriatal transmission during outcomes and actions in alcohol dependence
AID  - 10.1101/2020.12.04.411819
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.04.411819
4099  - http://biorxiv.org/content/early/2020/12/04/2020.12.04.411819.short
4100  - http://biorxiv.org/content/early/2020/12/04/2020.12.04.411819.full
AB  - Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyper-activity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively, however, the underlying mechanisms are unknown. Here we show that alcohol dependence enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid (eCB) signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation specific mechanism gating OFC activity following the induction of alcohol dependence.