Rafael Renteria, Christian Cazares, Emily T Baltz, Drew C Schreiner, Ege A Yalcinbas, Thomas Steinkellner, Thomas S Hnasko, Christina M Gremel
eLife 2021 Mar 17Psychiatric 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 hyperactivity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively; however, the underlying mechanisms are unknown. Here we show that alcohol-exposed mice have 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 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 in alcohol-exposed mice. © 2021, Renteria et al.
Rafael Renteria, Christian Cazares, Emily T Baltz, Drew C Schreiner, Ege A Yalcinbas, Thomas Steinkellner, Thomas S Hnasko, Christina M Gremel. Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure. eLife. 2021 Mar 17;10
PMID: 33729155
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