Globus pallidus dynamics reveal covert strategies for behavioral inhibition

  1. Bon-Mi Gu
  2. Robert Schmidt
  3. Joshua D Berke  Is a corresponding author
  1. UCSF, United States
  2. University of Sheffield, Germany

Abstract

Flexible behavior requires restraint of actions that are no longer appropriate. This behavioral inhibition critically relies on frontal cortex - basal ganglia circuits. Within the basal ganglia the globus pallidus pars externa (GPe), has been hypothesized to mediate selective proactive inhibition: being prepared to stop a specific action, if needed. Here we investigate population dynamics of rat GPe neurons during preparation-to-stop, stopping, and going. Rats selectively engaged proactive inhibition towards specific actions, as shown by slowed reaction times (RTs). Under proactive inhibition, GPe population activity occupied state-space locations farther from the trajectory followed during normal movement initiation. Furthermore, the state-space locations were predictive of distinct types of errors: failures-to-stop, failures-to-go, and incorrect choices. Slowed RTs on correct proactive trials reflected starting bias towards the alternative action, which was overcome before progressing towards action initiation. Our results demonstrate that rats can exert cognitive control via strategic adjustments to their GPe network state.

Data availability

Data and Code Availability. The neurophysiology data and analysis code used in this study are available from the to the public website Figshare: https://figshare.com/articles/Globus_pallidus_dynamics_reveal_covert_strategies_for_behavioral_inhibition/12367541

Article and author information

Author details

  1. Bon-Mi Gu

    Neurology, UCSF, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Robert Schmidt

    Department of Psychology, University of Sheffield, Sheffield, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Joshua D Berke

    Neurology, UCSF, San Francisco, United States
    For correspondence
    joshua.berke@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1436-6823

Funding

National Institute of Mental Health (R01 MH101697)

  • Joshua D Berke

National Institute on Drug Abuse (R01 DA045783)

  • Joshua D Berke

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were approved by the University of California, San Francisco Committee for the Use and Care of Animals (approval number: AN181071).

Copyright

© 2020, Gu 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

  • 1,865
    views
  • 354
    downloads
  • 23
    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. Bon-Mi Gu
  2. Robert Schmidt
  3. Joshua D Berke
(2020)
Globus pallidus dynamics reveal covert strategies for behavioral inhibition
eLife 9:e57215.
https://doi.org/10.7554/eLife.57215

Share this article

https://doi.org/10.7554/eLife.57215

Further reading

    1. Neuroscience
    Mina Mišić, Noah Lee ... Herta Flor
    Research Article

    Chronic back pain (CBP) is a global health concern with significant societal and economic burden. While various predictors of back pain chronicity have been proposed, including demographic and psychosocial factors, neuroimaging studies have pointed to brain characteristics as predictors of CBP. However, large-scale, multisite validation of these predictors is currently lacking. In two independent longitudinal studies, we examined white matter diffusion imaging data and pain characteristics in patients with subacute back pain (SBP) over 6- and 12-month periods. Diffusion data from individuals with CBP and healthy controls (HC) were analyzed for comparison. Whole-brain tract-based spatial statistics analyses revealed that a cluster in the right superior longitudinal fasciculus (SLF) tract had larger fractional anisotropy (FA) values in patients who recovered (SBPr) compared to those with persistent pain (SBPp), and predicted changes in pain severity. The SLF FA values accurately classified patients at baseline and follow-up in a third publicly available dataset (Area under the Receiver Operating Curve ~0.70). Notably, patients who recovered had FA values larger than those of HC suggesting a potential role of SLF integrity in resilience to CBP. Structural connectivity-based models also classified SBPp and SBPr patients from the three data sets (validation accuracy 67%). Our results validate the right SLF as a robust predictor of CBP development, with potential for clinical translation. Cognitive and behavioral processes dependent on the right SLF, such as proprioception and visuospatial attention, should be analyzed in subacute stages as they could prove important for back pain chronicity.

    1. Neuroscience
    Lian Hollander-Cohen, Omer Cohen ... Berta Levavi-Sivan
    Research Article

    Life histories of oviparous species dictate high metabolic investment in the process of gonadal development leading to ovulation. In vertebrates, these two distinct processes are controlled by the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively. While it was suggested that a common secretagogue, gonadotropin-releasing hormone (GnRH), oversees both functions, the generation of loss-of-function fish challenged this view. Here, we reveal that the satiety hormone cholecystokinin (CCK) is the primary regulator of this axis in zebrafish. We found that FSH cells express a CCK receptor, and our findings demonstrate that mutating this receptor results in a severe hindrance to ovarian development. Additionally, it causes a complete shutdown of both gonadotropins secretion. Using in-vivo and ex-vivo calcium imaging of gonadotrophs, we show that GnRH predominantly activates LH cells, whereas FSH cells respond to CCK stimulation, designating CCK as the bona fide FSH secretagogue. These findings indicate that the control of gametogenesis in fish was placed under different neural circuits, that are gated by CCK.