Viral vector-mediated selective and reversible blockade of the pathway for visual orienting in mice
Open accessAbstract
Recently, by using a combination of two viral vectors, we developed a technique for pathway-selective and reversible synaptic transmission blockade, and successfully induced a behavioral deficit of dexterous hand movements in macaque monkeys by affecting a population of spinal interneurons. To explore the capacity of this technique to work in other pathways and species, and to obtain fundamental methodological information, we tried to block the crossed tecto-reticular pathway, which is known to control orienting responses to visual targets, in mice. A neuron-specific retrograde gene transfer vector with the gene encoding enhanced tetanus neurotoxin (eTeNT) tagged with enhanced green fluorescent protein (EGFP) under the control of a tetracycline responsive element was injected into the left medial pontine reticular formation. 7-17 days later, an adeno-associated viral vector with a highly efficient Tet-ON sequence, rtTAV16, was injected into the right superior colliculus. 5-9 weeks later, the daily administration of doxycycline (Dox) was initiated. Visual orienting responses toward the left side were impaired 1-4 days after Dox administration. Anti-GFP immunohistochemistry revealed that a number of neurons in the intermediate and deep layers of the right superior colliculus were positively stained, indicating eTeNT expression. After the termination of Dox administration, the anti-GFP staining returned to the baseline level within 28 days. A second round of Dox administration, starting from 28 days after the termination of the first Dox administration, resulted in the reappearance of the behavioral impairment. These findings showed that pathway-selective and reversible blockade of synaptic transmission also causes behavioral effects in rodents, and that the crossed tecto-reticular pathway clearly controls visual orienting behaviors.
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Recent studies successfully applied V16 to control transgene expression in mice and non-human primates.
“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 [85]
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- Authors
- Sooksawate, T., Isa, K., Matsui, R., Kato, S., Kinoshita, M., Kobayashi, K., Watanabe, D., Kobayashi, K., & Isa, T.
- Affiliations
- Chulalongkorn University (TH)
- National Institute for Physiological Sciences (JP)
- Kyoto University (JP)
- Fukushima Medical University (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Corresponding author
- Sooksawate, Thongchai
- Isa, Tadashi
- ORCID
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 7
- Pages
- 162-162
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC3795302
- OpenAlex
- W1996084629
- Cited by
- 46
- References
- 44
- Citations by year
- 2025: 6 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 10 · 2014: 3
- FWCI
- 3.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (24220009, 25560436)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- visual orienting, adeno-associated virus vectors, tetracycline-inducible expression, superior colliculus, doxycycline
- MeSH terms
- Animals, Genetic Vectors, Synaptic Transmission, Neurons, Orientation, Reticular Formation, Superior Colliculi, Visual Perception, Mice
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