Serotonergic neurons signal reward and punishment on multiple timescales

  1. Jeremiah Y Cohen  Is a corresponding author
  2. Mackenzie W Amoroso
  3. Naoshige Uchida
  1. Harvard University, United States

Abstract

Serotonin's function in the brain is unclear. One challenge in testing the numerous hypotheses about serotonin's function has been observing the activity of identified serotonergic neurons in animals engaged in behavioral tasks. We recorded the activity of dorsal raphe neurons while mice experienced a task in which rewards and punishments varied across blocks of trials. We 'tagged' serotonergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to light. We found three main features of serotonergic neuron activity: (1) a large fraction of serotonergic neurons modulated their tonic firing rates over the course of minutes during reward versus punishment blocks; (2) most were phasically excited by punishments; and (3) a subset was phasically excited by reward-predicting cues. By contrast, dopaminergic neurons did not show firing rate changes across blocks of trials. These results suggest that serotonergic neurons signal information about reward and punishment on multiple timescales.

Article and author information

Author details

  1. Jeremiah Y Cohen

    Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States
    For correspondence
    jeremiah.cohen@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.
  2. Mackenzie W Amoroso

    Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Naoshige Uchida

    Department of Molecular and Cellular Biology, Center for Brain Science, Harvard University, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Timothy Behrens, Oxford University, United Kingdom

Ethics

Animal experimentation: All surgical and experimental procedures were in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Harvard or Johns Hopkins Institutional Animal Care and Use Committees.

Version history

  1. Received: January 6, 2015
  2. Accepted: February 24, 2015
  3. Accepted Manuscript published: February 25, 2015 (version 1)
  4. Version of Record published: April 8, 2015 (version 2)

Copyright

© 2015, Cohen 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

  • 9,921
    views
  • 2,842
    downloads
  • 270
    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. Jeremiah Y Cohen
  2. Mackenzie W Amoroso
  3. Naoshige Uchida
(2015)
Serotonergic neurons signal reward and punishment on multiple timescales
eLife 4:e06346.
https://doi.org/10.7554/eLife.06346

Share this article

https://doi.org/10.7554/eLife.06346

Further reading

    1. Neuroscience
    Amanda Chu, Nicholas T Gordon ... Michael A McDannald
    Research Article

    Pavlovian fear conditioning has been extensively used to study the behavioral and neural basis of defensive systems. In a typical procedure, a cue is paired with foot shock, and subsequent cue presentation elicits freezing, a behavior theoretically linked to predator detection. Studies have since shown a fear conditioned cue can elicit locomotion, a behavior that - in addition to jumping, and rearing - is theoretically linked to imminent or occurring predation. A criticism of studies observing fear conditioned cue-elicited locomotion is that responding is non-associative. We gave rats Pavlovian fear discrimination over a baseline of reward seeking. TTL-triggered cameras captured 5 behavior frames/s around cue presentation. Experiment 1 examined the emergence of danger-specific behaviors over fear acquisition. Experiment 2 examined the expression of danger-specific behaviors in fear extinction. In total, we scored 112,000 frames for nine discrete behavior categories. Temporal ethograms show that during acquisition, a fear conditioned cue suppresses reward seeking and elicits freezing, but also elicits locomotion, jumping, and rearing - all of which are maximal when foot shock is imminent. During extinction, a fear conditioned cue most prominently suppresses reward seeking, and elicits locomotion that is timed to shock delivery. The independent expression of these behaviors in both experiments reveal a fear conditioned cue to orchestrate a temporally organized suite of behaviors.

    1. Neuroscience
    Salima Messaoudi, Ada Allam ... Isabelle Caille
    Research Article

    The fragile X syndrome (FXS) represents the most prevalent form of inherited intellectual disability and is the first monogenic cause of autism spectrum disorder. FXS results from the absence of the RNA-binding protein FMRP (fragile X messenger ribonucleoprotein). Neuronal migration is an essential step of brain development allowing displacement of neurons from their germinal niches to their final integration site. The precise role of FMRP in neuronal migration remains largely unexplored. Using live imaging of postnatal rostral migratory stream (RMS) neurons in Fmr1-null mice, we observed that the absence of FMRP leads to delayed neuronal migration and altered trajectory, associated with defects of centrosomal movement. RNA-interference-induced knockdown of Fmr1 shows that these migratory defects are cell-autonomous. Notably, the primary Fmrp mRNA target implicated in these migratory defects is microtubule-associated protein 1B (MAP1B). Knocking down MAP1B expression effectively rescued most of the observed migratory defects. Finally, we elucidate the molecular mechanisms at play by demonstrating that the absence of FMRP induces defects in the cage of microtubules surrounding the nucleus of migrating neurons, which is rescued by MAP1B knockdown. Our findings reveal a novel neurodevelopmental role for FMRP in collaboration with MAP1B, jointly orchestrating neuronal migration by influencing the microtubular cytoskeleton.