Letter | Published:

Genetic dissection of the circuit for hand dexterity in primates

Nature volume 487, pages 235238 (12 July 2012) | Download Citation


It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates1,2,3. However, the role of the ‘phylogenetically older’ indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs)4,5,6, which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex–PN–motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.

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We thank S. Nakanishi, H. Jingami and C. Akazawa for continuous encouragement. We thank P. Redgrave for comments on the earlier version of the manuscript. This study was supported by the Strategic Research Program for Brain Sciences by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan. B.A. was supported by the Swedish Research Council. We thank T. Oishi for providing macaque brain sample tissue. We thank P. Phongphanphanee, M. Togawa, Y. Yamanishi, T. Katoh, K. Shimizu, N. Takahashi and K. Takada for technical support.

Author information


  1. Department of Developmental Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan

    • Masaharu Kinoshita
    • , Kaoru Isa
    • , Yukio Nishimura
    •  & Tadashi Isa
  2. Department of Molecular and System Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

    • Ryosuke Matsui
    • , Taku Hasegawa
    • , Hironori Kasahara
    •  & Dai Watanabe
  3. Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan

    • Shigeki Kato
    •  & Kazuto Kobayashi
  4. Division of Brain Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan

    • Akiya Watakabe
    •  & Tetsuo Yamamori
  5. The Graduate University for Advanced Studies (Sokendai), Hayama, Kanagawa 240-0193, Japan

    • Akiya Watakabe
    • , Tetsuo Yamamori
    • , Yukio Nishimura
    •  & Tadashi Isa
  6. Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Chiyoda, Tokyo 102-0076, Japan

    • Yukio Nishimura
  7. Department of Integrative Medical Biology, section of Physiology, Umeå University, S-901 87 Umeå, Sweden

    • Bror Alstermark


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Author Contributions M.K., D.W., K.K., B.A. and T.I. designed the experiments and wrote the paper. M.K., B.A., K.I. and T.I. conducted the surgery, behavioural, electrophysiological and histological experiments and analysed the data. R.M., T.H., S.K., H.K., D.W. and K.K. made the viral vectors. A.W. and T.Y. contributed to the histological processing. Y.N. contributed to behavioural analysis and electrophysiological experiments.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Tadashi Isa.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    This file contains Supplementary Figures 1-8, Supplementary Tables 1-2, and Supplementary References.


  1. 1.

    Supplementary Movie 1

    This movie shows examples of “precision grip errors” in monkey H.

  2. 2.

    Supplementary Movie 2

    This movie shows examples of “slit-hit errors” in monkey K.

  3. 3.

    Supplementary Movie 3

    This movie shows examples of “wandering errors” in monkey K.

  4. 4.

    Supplementary Movie 4

    This movie shows movement deficit and recovery in monkey H, which mainly showed “precision grip errors”. Reach and grasp movements of monkey H, on days 0, 2, and 5 after the start of Dox administration. Note that extension of the thumb was impaired on day 2, but the movements became normal again on day 5.

  5. 5.

    Supplementary Movie 5

    This movie shows movement deficit and recovery in monkey K, which mainly showed “slit-hit errors” and “wandering errors”. Reach and grasp movements of monkey K on days 0, 4, and 8 of the first Dox round (Dox1), days 3 and 7 of the 2nd Dox round (Dox2) and days 2 and 5.5 of the 3rd Dox round (Dox3). Note that the deficit in reaching was repeated and recovered.

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