1. Neuroscience
Download icon

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
Research Article
  • Cited 124
  • Views 9,887
  • Annotations
Cite this article as: eLife 2015;4:e10032 doi: 10.7554/eLife.10032

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

Publication 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

  • 9,887
    Page views
  • 2,638
    Downloads
  • 124
    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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Neuroscience
    Pratish Thakore et al.
    Research Article Updated

    Cerebral blood flow is dynamically regulated by neurovascular coupling to meet the dynamic metabolic demands of the brain. We hypothesized that TRPA1 channels in capillary endothelial cells are stimulated by neuronal activity and instigate a propagating retrograde signal that dilates upstream parenchymal arterioles to initiate functional hyperemia. We find that activation of TRPA1 in capillary beds and post-arteriole transitional segments with mural cell coverage initiates retrograde signals that dilate upstream arterioles. These signals exhibit a unique mode of biphasic propagation. Slow, short-range intercellular Ca2+ signals in the capillary network are converted to rapid electrical signals in transitional segments that propagate to and dilate upstream arterioles. We further demonstrate that TRPA1 is necessary for functional hyperemia and neurovascular coupling within the somatosensory cortex of mice in vivo. These data establish endothelial cell TRPA1 channels as neuronal activity sensors that initiate microvascular vasodilatory responses to redirect blood to regions of metabolic demand.

    1. Neuroscience
    Timothy S Balmer et al.
    Research Article Updated

    Synapses of glutamatergic mossy fibers (MFs) onto cerebellar unipolar brush cells (UBCs) generate slow excitatory (ON) or inhibitory (OFF) postsynaptic responses dependent on the complement of glutamate receptors expressed on the UBC’s large dendritic brush. Using mouse brain slice recording and computational modeling of synaptic transmission, we found that substantial glutamate is maintained in the UBC synaptic cleft, sufficient to modify spontaneous firing in OFF UBCs and tonically desensitize AMPARs of ON UBCs. The source of this ambient glutamate was spontaneous, spike-independent exocytosis from the MF terminal, and its level was dependent on activity of glutamate transporters EAAT1–2. Increasing levels of ambient glutamate shifted the polarity of evoked synaptic responses in ON UBCs and altered the phase of responses to in vivo-like synaptic activity. Unlike classical fast synapses, receptors at the UBC synapse are virtually always exposed to a significant level of glutamate, which varies in a graded manner during transmission.