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Review
. 2021 Apr;99(4):981-990.
doi: 10.1002/jnr.24774. Epub 2020 Dec 20.

Intersectional targeting of defined neural circuits by adeno-associated virus vectors

Chase A Weinholtz  1 , Michael J Castle  2
Affiliations
Review

Intersectional targeting of defined neural circuits by adeno-associated virus vectors

Chase A Weinholtz et al. J Neurosci Res. 2021 Apr.

Abstract

The mammalian nervous system is a complex network of interconnected cells. We review emerging techniques that use the axonal transport of adeno-associated virus (AAV) vectors to dissect neural circuits. These intersectional approaches specifically target AAV-mediated gene expression to discrete neuron populations based on their axonal connectivity, including: (a) neurons with one defined output, (b) neurons with one defined input, (c) neurons with one defined input and one defined output, and (d) neurons with two defined inputs or outputs. The number of labeled neurons can be directly controlled to trace axonal projections and examine cellular morphology. These approaches can precisely target the expression of fluorescent reporters, optogenetic ion channels, chemogenetic receptors, disease-associated proteins, and other factors to defined neural circuits in mammals ranging from mice to macaques, and thereby provide a powerful new means to understand the structure and function of the nervous system.

Keywords: AAV; anterograde; axonal transport; intersectional; neural circuits; retrograde.

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Conflict of interest statement

Conflict of Interest Statement

The authors declare that no conflict of interest exists.

Figures

Figure 1.
Figure 1.. Intersectional Targeting of Defined Neural Circuits.
(A) Targeting gene expression to neurons with one defined output by retrograde transport of AAV2-retro-hSyn1-Cre. (B) Targeting gene expression to neurons with one defined input by anterograde trans-synaptic transport of AAV1-hSyn1-Cre. (C) Targeting gene expression to neurons with one defined input and one defined output by anterograde trans-synaptic transport of AAV1-hSyn1-Cre and retrograde transport of Cre-dependent AAV2-retro. (D) Targeting gene expression to neurons with two defined inputs by anterograde trans-synaptic transport of both AAV1-hSyn1-Cre and AAV1-hSyn1-Flp.
Figure 2.
Figure 2.. Controlling the Number of Labeled Neurons.
The number of labeled neurons can be directly controlled by local injection of a Cre-dependent AAV-CIAO-Flp vector, which acts as a gate between anterograde trans-synaptic delivery of AAV1-hSyn1-Cre and a Flp-dependent vector such as AAV-FlpDIO-tdTomato. Because only cells that receive AAV-CIAO-Flp can activate gene expression, reducing the dose of this vector reduces the number of labeled cells without altering the strength of gene expression.
See this image and copyright information in PMC

References

    1. Amin SR, Gruszczynski C, Guiard BP, Callebert J, Launay J-M, Louis F, Betancur C, Vialou V, and Gautron S. (2019). Viral vector-mediated Cre recombinase expression in substantia nigra induces lesions of the nigrostriatal pathway associated with perturbations of dopamine-related behaviors and hallmarks of programmed cell death. J. Neurochem. 150 (3), 330–340. doi: 10.1111/jnc.14684. - DOI - PubMed
    1. An K, Zhao H, Miao Y, Xu Q, Li Y-F, Ma Y-Q, Shi Y-M, Shen J-W, Meng J-J, Yao Y-G, Zhang Z, Chen J-T, Bao J, Zhang M, and Xue T. (2020). A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice. Nat. Neurosci. 23 (7), 869–880. doi: 10.1038/s41593-020-0640-8. - DOI - PubMed
    1. Archin NM, and Atherton SS (2002). Rapid spread of a neurovirulent strain of HSV-1 through the CNS of BALB/c mice following anterior chamber inoculation. J. Neurovirol. 8 (2), 122–135. doi: 10.1080/13550280290049570. - DOI - PubMed
    1. Atchison RW, Casto BC, and Hammon WM (1965). Adenovirus-associated Defective Virus Particles. Science 149 (3685), 754–756. doi: 10.1126/science.149.3685.754. - DOI - PubMed
    1. Azim E, Jiang J, Alstermark B, and Jessell TM (2014). Skilled reaching relies on a V2a propriospinal internal copy circuit. Nature 508 (7496), 357–363. doi: 10.1038/nature13021. - DOI - PMC - PubMed

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