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Genetic dissection of the circuit for hand dexterity in primates
Abstract
It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. 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), 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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“Recent studies successfully applied V16 to control transgene expression in mice [85, 86] and non-human primates [62, 87].”
From Tet-On Systems For Doxycycline-inducible Gene Expression (2016) · cites this paper as [87]
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Metadata
- Authors
- Kinoshita, M., Matsui, R., Kato, S., Hasegawa, T., Kasahara, H., Isa, K., Watakabe, A., Yamamori, T., Nishimura, Y., Alstermark, B., Watanabe, D., Kobayashi, K., & Isa, T.
- Affiliations
- National Institute for Physiological Sciences (JP)
- Kyoto University (JP)
- Fukushima Medical University (JP)
- National Institute for Basic Biology (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Umeå University (SE)
- Corresponding author
- Isa, Tadashi
- ORCID
- Venue
- Nature
- Published
- 2012-06-17
- Volume
- 487
- Issue
- 7406
- Pages
- 235-238
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2052129348
- Cited by
- 259
- References
- 34
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 9 · 2023: 11 · 2022: 18 · 2021: 26 · 2020: 15 · 2019: 31 · 2018: 17 · 2017: 16 · 2016: 20 · 2015: 26 · 2014: 20 · 2013: 20 · 2012: 5
- FWCI
- 11.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Vetenskapsrådet
- Japan Society for the Promotion of Science (22123009, 24220009, 20240030)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- manual dexterity, propriospinal neurons, motor cortex, spinal interneurons, tetanus neurotoxin, viral vectors, adeno-associated virus, synaptic transmission blockade, macaque
- MeSH terms
- Dependovirus, Animals, Hand, Macaca, Metalloendopeptidases, Motor Cortex, Motor Neurons, Synaptic Transmission, Neurosciences, Tetanus Toxin, Green Fluorescent Proteins
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