Dopaminergic challenge dissociates learning from primary versus secondary sources of information

  1. Alicia J Rybicki  Is a corresponding author
  2. Sophie L Sowden
  3. Bianca Schuster
  4. Jennifer L Cook
  1. University of Birmingham, United Kingdom

Abstract

Some theories of human cultural evolution posit that humans have social-specific learning mechanisms that are adaptive specialisations moulded by natural selection to cope with the pressures of group living. However, the existence of neurochemical pathways that are specialised for learning from social information and from individual experience is widely debated. Cognitive neuroscientific studies present mixed evidence for social-specific learning mechanisms: some studies find dissociable neural correlates for social and individual learning whereas others find the same brain areas and, dopamine-mediated, computations involved in both. Here we demonstrate that, like individual learning, social learning is modulated by the dopamine D2 receptor antagonist haloperidol when social information is the primary learning source, but not when it comprises a secondary, additional element. Two groups (total N = 43) completed a decision-making task which required primary learning, from own experience, and secondary learning from an additional source. For one group the primary source was social, and secondary was individual; for the other group this was reversed. Haloperidol affected primary learning irrespective of social/individual nature, with no effect on learning from the secondary source. Thus, we illustrate that dopaminergic mechanisms underpinning learning can be dissociated along a primary-secondary but not a social-individual axis. These results resolve conflict in the literature and support an expanding field showing that, rather than being specialised for particular inputs, neurochemical pathways in the human brain can process both social and non-social cues and arbitrate between the two depending upon which cue is primarily relevant for the task at hand.

Data availability

All raw data and analysis scripts can be accessed at the Open Science Framework data repository:​​https://osf.io/398w4/?view_only=08c062a9694a4b00ac7cbc52ee333628

Article and author information

Author details

  1. Alicia J Rybicki

    University of Birmingham, Birmingham, United Kingdom
    For correspondence
    axr783@bham.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6668-1214
  2. Sophie L Sowden

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9913-0515
  3. Bianca Schuster

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Jennifer L Cook

    University of Birmingham, Birmingham, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4916-8667

Funding

Biotechnology and Biological Sciences Research Council (Midlands Integrative Biosciences Training Partnership (MIBTP) Doctoral Funding)

  • Alicia J Rybicki

H2020 European Research Council (757583 - Brain2Bee)

  • Sophie L Sowden
  • Bianca Schuster
  • Jennifer L Cook

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

Reviewing Editor

  1. Steve W C Chang, Yale University, United States

Ethics

Human subjects: Informed consent was obtained from each subject. The study was in line with the local ethical guidelines approved by the local ethics committee (ERN_18_1588) and in accordance with the Helsinki Declaration of 1975.

Version history

  1. Received: October 20, 2021
  2. Preprint posted: December 3, 2021 (view preprint)
  3. Accepted: March 14, 2022
  4. Accepted Manuscript published: March 15, 2022 (version 1)
  5. Accepted Manuscript updated: March 16, 2022 (version 2)
  6. Version of Record published: April 21, 2022 (version 3)

Copyright

© 2022, Rybicki 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

  • 1,311
    views
  • 142
    downloads
  • 10
    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. Alicia J Rybicki
  2. Sophie L Sowden
  3. Bianca Schuster
  4. Jennifer L Cook
(2022)
Dopaminergic challenge dissociates learning from primary versus secondary sources of information
eLife 11:e74893.
https://doi.org/10.7554/eLife.74893

Share this article

https://doi.org/10.7554/eLife.74893

Further reading

    1. Biochemistry and Chemical Biology
    2. Neuroscience
    Katarzyna Marta Zoltowska, Utpal Das ... Lucía Chávez-Gutiérrez
    Research Article

    Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer’s disease (AD). However, molecular cascades underlying their toxicity are poorly defined. Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aβ42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events. We conducted kinetic analyses of γ-secretase activity in cell-free systems in the presence of Aβ, as well as cell-based and ex vivo assays in neuronal cell lines, neurons, and brain synaptosomes to assess the impact of Aβ on γ-secretases. We show that human Aβ42 peptides, but neither murine Aβ42 nor human Aβ17–42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75, and pan-cadherin. Moreover, Aβ42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems. Our findings raise the possibility that pathological elevations in Aβ42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aβ toxicity in the context of γ-secretase-dependent homeostatic signaling.

    1. Computational and Systems Biology
    2. Neuroscience
    Sara Ibañez, Nilapratim Sengupta ... Christina M Weaver
    Research Article

    Normal aging leads to myelin alterations in the rhesus monkey dorsolateral prefrontal cortex (dlPFC), which are positively correlated with degree of cognitive impairment. It is hypothesized that remyelination with shorter and thinner myelin sheaths partially compensates for myelin degradation, but computational modeling has not yet explored these two phenomena together systematically. Here, we used a two-pronged modeling approach to determine how age-related myelin changes affect a core cognitive function: spatial working memory. First, we built a multicompartment pyramidal neuron model fit to monkey dlPFC empirical data, with an axon including myelinated segments having paranodes, juxtaparanodes, internodes, and tight junctions. This model was used to quantify conduction velocity (CV) changes and action potential (AP) failures after demyelination and subsequent remyelination. Next, we incorporated the single neuron results into a spiking neural network model of working memory. While complete remyelination nearly recovered axonal transmission and network function to unperturbed levels, our models predict that biologically plausible levels of myelin dystrophy, if uncompensated by other factors, can account for substantial working memory impairment with aging. The present computational study unites empirical data from ultrastructure up to behavior during normal aging, and has broader implications for many demyelinating conditions, such as multiple sclerosis or schizophrenia.