Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

  1. William Menegas
  2. Joseph F Bergan
  3. Sachie K Ogawa
  4. Yoh Isogai
  5. Kannan Umadevi Venkataraju
  6. Pavel Osten
  7. Naoshige Uchida
  8. Mitsuko Watabe-Uchida  Is a corresponding author
  1. Harvard University, United States
  2. University of Massachusetts Amherst, United States
  3. Massachusetts Institute of Technology, United States
  4. Cold Spring Harbor Laboratory, United States

Abstract

Combining rabies-virus tracing, optical clearing (CLARITY), and whole-brain light-sheet imaging, we mapped the monosynaptic inputs to midbrain dopamine neurons projecting to different targets (different parts of the striatum, cortex, amygdala, etc.) in mice. We found that most populations of dopamine neurons receive a similar set of inputs rather than forming strong reciprocal connections with their target areas. A common feature among most populations of dopamine neurons was the existence of dense 'clusters' of inputs within the ventral striatum. However, we found that dopamine neurons projecting to the posterior striatum were outliers, receiving relatively few inputs from the ventral striatum and instead receiving more inputs from the globus pallidus, subthalamic nucleus, and zona incerta. These results lay a foundation for understanding the input/output structure of the midbrain dopamine circuit and demonstrate that dopamine neurons projecting to the posterior striatum constitute a unique class of dopamine neurons regulated by different inputs.

Article and author information

Author details

  1. William Menegas

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Joseph F Bergan

    Department of Psychological and Brain Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    Joseph F Bergan, Yoh Isogai and Joseph Bergan have filed a patent application on OptiView.
  3. Sachie K Ogawa

    RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    No competing interests declared.
  4. Yoh Isogai

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    Yoh Isogai, Yoh Isogai and Joseph Bergan have filed a patent application on OptiView.
  5. Kannan Umadevi Venkataraju

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    No competing interests declared.
  6. Pavel Osten

    Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    No competing interests declared.
  7. Naoshige Uchida

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    Competing interests
    Naoshige Uchida, Reviewing editor, eLife.
  8. Mitsuko Watabe-Uchida

    Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States
    For correspondence
    mitsuko@mcb.harvard.edu
    Competing interests
    No competing interests declared.

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 of the animals were handled according to approved Harvard animal care and use committee (IACUC) protocols (#26-03) of Harvard University. All surgery was performed under isofluorane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Sacha B Nelson, Brandeis University, United States

Version history

  1. Received: July 11, 2015
  2. Accepted: August 28, 2015
  3. Accepted Manuscript published: August 31, 2015 (version 1)
  4. Version of Record published: October 9, 2015 (version 2)

Copyright

© 2015, Menegas 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

  • 13,202
    Page views
  • 3,049
    Downloads
  • 209
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

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. William Menegas
  2. Joseph F Bergan
  3. Sachie K Ogawa
  4. Yoh Isogai
  5. Kannan Umadevi Venkataraju
  6. Pavel Osten
  7. Naoshige Uchida
  8. Mitsuko Watabe-Uchida
(2015)
Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass
eLife 4:e10032.
https://doi.org/10.7554/eLife.10032

Share this article

https://doi.org/10.7554/eLife.10032

Further reading

    1. Developmental Biology
    2. Neuroscience
    Simon Desiderio, Frederick Schwaller ... Frederic Marmigere
    Research Article

    Touch sensation is primarily encoded by mechanoreceptors, called low-threshold mechanoreceptors (LTMRs), with their cell bodies in the dorsal root ganglia. Because of their great diversity in terms of molecular signature, terminal endings morphology, and electrophysiological properties, mirroring the complexity of tactile experience, LTMRs are a model of choice to study the molecular cues differentially controlling neuronal diversification. While the transcriptional codes that define different LTMR subtypes have been extensively studied, the molecular players that participate in their late maturation and in particular in the striking diversity of their end-organ morphological specialization are largely unknown. Here we identified the TALE homeodomain transcription factor Meis2 as a key regulator of LTMRs target-field innervation in mice. Meis2 is specifically expressed in cutaneous LTMRs, and its expression depends on target-derived signals. While LTMRs lacking Meis2 survived and are normally specified, their end-organ innervations, electrophysiological properties, and transcriptome are differentially and markedly affected, resulting in impaired sensory-evoked behavioral responses. These data establish Meis2 as a major transcriptional regulator controlling the orderly formation of sensory neurons innervating peripheral end organs required for light touch.

    1. Neuroscience
    Maureen van der Grinten, Jaap de Ruyter van Steveninck ... Yağmur Güçlütürk
    Tools and Resources

    Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or ‘phosphenes’) has limited resolution, and a great portion of the field’s research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator’s suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.