Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure
- University of California, San Diego, United States
Abstract
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 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 (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 in alcohol exposed mice.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files. Source data for all figures has been provided.
Article and author information
Author details
Christina M Gremel
Funding
National Institutes of Health (AA026077-01A1)
- Christina M Gremel
National Institutes of Health (F32 AA026776)
- Rafael Renteria
National Science Foundation (NSF-GRFP DGE-2038238)
- Emily T Baltz
National Science Foundation (NSF-GRFP DGE-1650112)
- Christian Cazares
National Institutes of Health (F31 AA027439)
- Drew C Schreiner
National Institutes of Health (R01DA036612)
- Thomas S Hnasko
National Institutes of Health (R01NS106822)
- Thomas S Hnasko
National Institutes of Health (T01BX003759)
- Thomas S Hnasko
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All experiments were approved by the Institutional Animal Care and Use Committees of the University of California San Diego and experiments were conducted according to NIH guidelines.
Copyright
© 2021, Renteria et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure
eLife 10:e67065.
https://doi.org/10.7554/eLife.67065
