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Three Types of A11 Neurons Project to the Rat Spinal Cord

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Abstract

The A11 dopaminergic cell group is the only group among the A8–A16 dopaminergic cell groups that includes neurons innervating the spinal cord, and a decrease in dopaminergic transmission at the spinal cord is thought to contribute to the pathogenesis of restless legs syndrome. However, the mechanisms regulating the neuronal activity of A11 dopaminergic neurons remain to be elucidated. Unraveling the neuronal composition, distribution and connectivity of A11 neurons would provide insights into the mechanisms regulating the spinal dopaminergic system. To address this, we performed immunohistochemistry for calcium-binding proteins such as calbindin (Calb) and parvalbumin (PV), in combination with the retrograde tracer Fluorogold (FG) injected into the spinal cord. Immunohistochemistry for Calb, PV, or tyrosine hydroxylase (TH), a marker for dopaminergic neurons, revealed that there were at least three types of neurons in the A11 region: neurons expressing Calb, TH, or both TH and Calb, whereas there were no PV-immunoreactive (IR) cell bodies. Both Calb- and PV-IR processes were found throughout the entire A11 region, extending in varied directions depending on the level relative to bregma. We found retrogradely labeled FG-positive neurons expressing TH, Calb, or both TH and Calb, as well as FG-positive neurons lacking both TH and Calb. These findings indicate that the A11 region is composed of a variety of neurons that are distinct in their neurochemical properties, and suggest that the diencephalospinal dopamine system may be regulated at the A11region by both Calb-IR and PV-IR processes, and at the terminal region of the spinal cord by Calb-IR processes derived from the A11 region.

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Acknowledgements

This work was supported by Dokkyo Medical University. H.O. is the recipient of a Young Investigator award (No. 2015-21) from Dokkyo Medical University. We would like to thank Shukuko Nihei for excellent technical assistance.

Funding

This study was funded by a Young Investigator Award (Grant No. 2015-21 for H.O.) from Dokkyo Medical University.

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    Authors and Affiliations

    1. Department of Anesthesiology, Dokkyo Medical University School of Medicine, Tochigi, Japan

      Hidechika Ozawa, Shinsuke Hamaguchi & Shigeki Yamaguchi

    2. Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, 880 Kita-kobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, 321-0293, Japan

      Tsuyoshi Yamaguchi & Shuichi Ueda

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    1. Hidechika Ozawa
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    2. Tsuyoshi Yamaguchi
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    Correspondence to Shuichi Ueda.

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    All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

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    Hidechika Ozawa and Tsuyoshi Yamaguchi have contributed equally to do this work.

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    Ozawa, H., Yamaguchi, T., Hamaguchi, S. et al. Three Types of A11 Neurons Project to the Rat Spinal Cord. Neurochem Res 42, 2142–2153 (2017). https://doi.org/10.1007/s11064-017-2219-7

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    • DOI: https://doi.org/10.1007/s11064-017-2219-7

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