Abstract

Functional diversity of midbrain dopamine (DA) neurons ranges across multiple scales, from differences in intrinsic properties and connectivity to selective task engagement in behaving animals. Distinct in vitro biophysical features of DA neurons have been associated with different axonal projection targets. However, it is unknown how this translates to different firing patterns of projection-defined DA subpopulations in the intact brain. We combined retrograde tracing with single-unit recording and labelling in mouse brain to create an in vivo functional topography of the midbrain DA system. We identified differences in burst firing among DA neurons projecting to dorsolateral striatum. Bursting also differentiated DA neurons in the medial substantia nigra (SN) projecting either to dorsal or ventral striatum. We found differences in mean firing rates and pause durations among ventral tegmental area (VTA) DA neurons projecting to lateral or medial shell of nucleus accumbens. Our data establishes a high-resolution functional in vivo landscape of midbrain DA neurons.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Navid Farassat

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. ​Kauê Machado Costa

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5562-6495
  3. Strahinja Stovanovic

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Stefan Albert

    Institute for Mathematics, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Lora Kovacheva

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Josef Shin

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Richard Egger

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Mahalakshmi Somayaji

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Sevil Duvarci

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  10. Gaby Schneider

    Institute for Mathematics, Goethe University Frankfurt, Frankfurt, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Jochen Roeper

    Institute for Neurophysiology, Goethe University Frankfurt, Frankfurt, Germany
    For correspondence
    roeper@em.uni-frankfurt.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2145-8742

Funding

National Institutes of Health (R01DA041705)

  • Jochen Roeper

Deutsche Forschungsgemeinschaft (CRC 1080)

  • Jochen Roeper

Gutenberg Forschungskolleg

  • Jochen Roeper

Deutsche Forschungsgemeinschaft (CRC 1193)

  • Jochen Roeper

Deutsche Forschungsgemeinschaft (DFG Priority Program 1665 (SCHN 1370/02-1))

  • Gaby Schneider

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 experiments and procedures involving mice were approved by the German Regierungspräsidium Darmstadt (V54-19c20/15-F40/28).

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 6,697
    views
  • 1,146
    downloads
  • 67
    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. Navid Farassat
  2. ​Kauê Machado Costa
  3. Strahinja Stovanovic
  4. Stefan Albert
  5. Lora Kovacheva
  6. Josef Shin
  7. Richard Egger
  8. Mahalakshmi Somayaji
  9. Sevil Duvarci
  10. Gaby Schneider
  11. Jochen Roeper
(2019)
In vivo functional diversity of midbrain dopamine neurons within identified axonal projections
eLife 8:e48408.
https://doi.org/10.7554/eLife.48408

Share this article

https://doi.org/10.7554/eLife.48408

Further reading

    1. Neuroscience
    Eleni Hackwell, Sharon R Ladyman ... David R Grattan
    Research Article

    The specific role that prolactin plays in lactational infertility, as distinct from other suckling or metabolic cues, remains unresolved. Here, deletion of the prolactin receptor (Prlr) from forebrain neurons or arcuate kisspeptin neurons resulted in failure to maintain normal lactation-induced suppression of estrous cycles. Kisspeptin immunoreactivity and pulsatile LH secretion were increased in these mice, even in the presence of ongoing suckling stimulation and lactation. GCaMP fibre photometry of arcuate kisspeptin neurons revealed that the normal episodic activity of these neurons is rapidly suppressed in pregnancy and this was maintained throughout early lactation. Deletion of Prlr from arcuate kisspeptin neurons resulted in early reactivation of episodic activity of kisspeptin neurons prior to a premature return of reproductive cycles in early lactation. These observations show dynamic variation in arcuate kisspeptin neuronal activity associated with the hormonal changes of pregnancy and lactation, and provide direct evidence that prolactin action on arcuate kisspeptin neurons is necessary for suppressing fertility during lactation in mice.

    1. Neuroscience
    Choongheon Lee, Mohammad Shokrian ... Jong-Hoon Nam
    Research Article

    We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid–structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently suggest that active outer hair cells in the tail region of cochlear traveling waves drive cochlear fluid circulation.