1. Neuroscience

Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure

  1. Rafael Renteria
  2. Christian Cazares
  3. Emily T Baltz
  4. Drew C Schreiner
  5. Ege A Yalcinbas
  6. Thomas Steinkellner
  7. Thomas S Hnasko
  8. Christina M Gremel  Is a corresponding author
  1. University of California, San Diego, United States
https://doi.org/10.7554/eLife.67065
Share this article
Cite this article
  1. Rafael Renteria
  2. Christian Cazares
  3. Emily T Baltz
  4. Drew C Schreiner
  5. Ege A Yalcinbas
  6. Thomas Steinkellner
  7. Thomas S Hnasko
  8. Christina M Gremel
(2021)
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
  2. Download BibTeX
  3. Download .RIS

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

  1. Rafael Renteria

    Department of Psychology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6199-0293

  2. Christian Cazares

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8899-2109

  3. Emily T Baltz

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9770-3666

  4. Drew C Schreiner

    Department of Psychology, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Ege A Yalcinbas

    The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9480-7192

  6. Thomas Steinkellner

    Department of Neurosciences, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Thomas S Hnasko

    Department of Neurosciences, The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6176-8513

  8. Christina M Gremel

    Department of Psychology, The Neurosciences Graduate Program, University of California, San Diego, La Jolla, United States
    For correspondence
    cgremel@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8710-0543

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.

Metrics

  • 1,476
    views
  • 173
    downloads
  • 22
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rafael Renteria
  2. Christian Cazares
  3. Emily T Baltz
  4. Drew C Schreiner
  5. Ege A Yalcinbas
  6. Thomas Steinkellner
  7. Thomas S Hnasko
  8. Christina M Gremel
(2021)
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

Share this article

https://doi.org/10.7554/eLife.67065

Categories and tags

Research organism

Further reading

    1. Computational and Systems Biology
    2. Neuroscience

    Neural population dynamics underlying evidence accumulation in multiple rat brain regions

    Brian DePasquale, Carlos D Brody, Jonathan W Pillow
    Research Article Updated

    Accumulating evidence to make decisions is a core cognitive function. Previous studies have tended to estimate accumulation using either neural or behavioral data alone. Here, we develop a unified framework for modeling stimulus-driven behavior and multi-neuron activity simultaneously. We applied our method to choices and neural recordings from three rat brain regions—the posterior parietal cortex (PPC), the frontal orienting fields (FOF), and the anterior-dorsal striatum (ADS)—while subjects performed a pulse-based accumulation task. Each region was best described by a distinct accumulation model, which all differed from the model that best described the animal’s choices. FOF activity was consistent with an accumulator where early evidence was favored while the ADS reflected near perfect accumulation. Neural responses within an accumulation framework unveiled a distinct association between each brain region and choice. Choices were better predicted from all regions using a comprehensive, accumulation-based framework and different brain regions were found to differentially reflect choice-related accumulation signals: FOF and ADS both reflected choice but ADS showed more instances of decision vacillation. Previous studies relating neural data to behaviorally inferred accumulation dynamics have implicitly assumed that individual brain regions reflect the whole-animal level accumulator. Our results suggest that different brain regions represent accumulated evidence in dramatically different ways and that accumulation at the whole-animal level may be constructed from a variety of neural-level accumulators.

    1. Neuroscience

    Cholesterol taste avoidance in Drosophila melanogaster

    Roshani Nhuchhen Pradhan, Craig Montell, Youngseok Lee
    Research Article

    The question as to whether animals taste cholesterol taste is not resolved. This study investigates whether the fruit fly, Drosophila melanogaster, is capable of detecting cholesterol through their gustatory system. We found that flies are indifferent to low levels of cholesterol and avoid higher levels. The avoidance is mediated by gustatory receptor neurons (GRNs), demonstrating that flies can taste cholesterol. The cholesterol-responsive GRNs comprise a subset that also responds to bitter substances. Cholesterol detection depends on five ionotropic receptor (IR) family members, and disrupting any of these genes impairs the flies' ability to avoid cholesterol. Ectopic expressions of these IRs in GRNs reveals two classes of cholesterol receptors, each with three shared IRs and one unique subunit. Additionally, expressing cholesterol receptors in sugar-responsive GRNs confers attraction to cholesterol. This study reveals that flies can taste cholesterol, and that the detection depends on IRs in GRNs.

    1. Neuroscience

    A general framework for characterizing optimal communication in brain networks

    Kayson Fakhar, Fatemeh Hadaeghi ... Claus C Hilgetag
    Research Article

    Efficient communication in brain networks is foundational for cognitive function and behavior. However, how communication efficiency is defined depends on the assumed model of signaling dynamics, e.g., shortest path signaling, random walker navigation, broadcasting, and diffusive processes. Thus, a general and model-agnostic framework for characterizing optimal neural communication is needed. We address this challenge by assigning communication efficiency through a virtual multi-site lesioning regime combined with game theory, applied to large-scale models of human brain dynamics. Our framework quantifies the exact influence each node exerts over every other, generating optimal influence maps given the underlying model of neural dynamics. These descriptions reveal how communication patterns unfold if regions are set to maximize their influence over one another. Comparing these maps with a variety of brain communication models showed that optimal communication closely resembles a broadcasting regime in which regions leverage multiple parallel channels for information dissemination. Moreover, we found that the brain’s most influential regions are its rich-club, exploiting their topological vantage point by broadcasting across numerous pathways that enhance their reach even if the underlying connections are weak. Altogether, our work provides a rigorous and versatile framework for characterizing optimal brain communication, and uncovers the most influential brain regions, and the topological features underlying their influence.