Fast Retrograde Access to Projection Neuron Circuits Underlying Vocal Learning in Songbirds

Düring, Daniel Normen; Dittrich, Falk; Rocha, Mariana Diales da; Tachibana, Ryosuke O.; Mori, Chihiro; Okanoya, Kazuo; Boehringer, Roman; Ehret, Benjamin; Grewe, Benjamin F.; Gerber, Stefan; Ma, Shouwen; Rauch, Melanie; Paterna, Jean-Charles; Kasper, Robert; Gahr, Manfred; Hahnloser, Richard H. R.

doi:10.1016/j.celrep.2020.108364

Cited by 27 publications

(19 citation statements)

References 62 publications

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“…These results indicate that PCs in lobules VIII–X directly project their axons to the ipsilateral MPB, but not those in lobules VI–VII (Hashimoto et al, 2018 ). Recently, retrograde properties have also been reported for serotype AAV2/DJ and mouse brain striatal injections, which targeted cells in the substantia nigra (Düring et al, 2020 ). The CNS retrograde capabilities of AAV2 and other serotypes are summarized in Table 1 (Itoga et al, 2019 ; Jara et al, 2012 ; Zheng et al, 2020 ).…”

Section: Introductionmentioning

confidence: 98%

Retrograde capabilities of adeno-associated virus vectors in the central nervous system

Surdyka¹,

Figiel²

2021

bta

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Adeno-associated virus (AAV) vectors delivered at the axonal terminals can be retrogradely transported toward neuronal cell bodies throughout the axons. This retrograde phenomenon can serve as a powerful tool for experiments and gene therapy using AAVs. The advantages of using AAV vectors delivered retrogradely are greater cellular specificity, high transduction efficiency, increased safety, and absence of cytotoxicity. The numerous axonal projections in the nervous system provide a neuronal network for the convenient and widespread distribution of viral vectors between adjacent brain structures and over long distances. The retrograde efficiency of AAVs in the neurons of the central nervous system (CNS) depends on AAV serotype, the region of injection, and the type of neurons. In this review, we describe AAV serotypes and their retrograde transport properties after injection and discuss brain structures or types of cells that are targeted for retrograde transport. In particular, AAV serotypes 2, 5, 8, 9, rh10, and PHP.eB are extensively reviewed as they demonstrate retrograde transport potential suitable for use in gene therapy applications.

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Section: Introductionmentioning

confidence: 98%

Retrograde capabilities of adeno-associated virus vectors in the central nervous system

Surdyka¹,

Figiel²

2021

bta

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“…It is well appreciated in the avian field that viral transduction of neurons in vivo is challenging 32 . However, a handful of recent reports show partial success following the use of common recombinant adeno-associated viruses, for instance, AAV1 in pigeons 32 , barn owls 14 and zebra finches 36 , 37 (and other serotypes in canaries 7 , finches 38 , and more 39 , 40 ). Thus, we first examined whether AAV1 would also be suitable for the transduction of neurons of Japanese quails in vivo.…”

Section: Resultsmentioning

confidence: 99%

A custom-made AAV1 variant (AAV1-T593K) enables efficient transduction of Japanese quail neurons in vitro and in vivo

et al. 2023

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The widespread use of rodents in neuroscience has prompted the development of optimized viral variants for transduction of brain cells, in vivo. However, many of the viruses developed are less efficient in other model organisms, with birds being among the most resistant to transduction by current viral tools. Resultantly, the use of genetically-encoded tools and methods in avian species is markedly lower than in rodents; likely holding the field back. We sought to bridge this gap by developing custom viruses towards the transduction of brain cells of the Japanese quail. We first develop a protocol for culturing primary neurons and glia from quail embryos, followed by characterization of cultures via immunostaining, single cell mRNA sequencing, patch clamp electrophysiology and calcium imaging. We then leveraged the cultures for the rapid screening of various viruses, only to find that all yielded poor to no infection of cells in vitro. However, few infected neurons were obtained by AAV1 and AAV2. Scrutiny of the sequence of the AAV receptor found in quails led us to rationally design a custom-made AAV variant (AAV1-T593K; AAV1*) that exhibits improved transduction efficiencies in vitro and in vivo (14- and five-fold, respectively). Together, we present unique culturing method, transcriptomic profiles of quail’s brain cells and a custom-tailored AAV1 for transduction of quail neurons in vitro and in vivo.

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“…Currently, AAV is among the most commonly used viruses for neuroscience research [52] and the leading platform for in vivo delivery of gene therapies [53], have been extensively used as vehicles for gene transfer to the nervous system enabling gene expression and knockdown, gene editing [54,55], circuit modulation [56,57], in vivo imaging [58,59], disease model development [60], and the evaluation of therapeutic candidates for the treatment of neurological diseases [18]. Focus on the application of AAV vectors in central nervous system related issues, in addition to the delivery of the gene of interest by in situ injection, the infection types of AAV mainly include across the blood-brain barrier via intravenous injection [61][62][63][64], anterograde transsynaptic spread [37], and retrograde labeling by axon terminal absorption [20][21][22][23]65].…”

Section: Discussionmentioning

confidence: 99%

AAV11 permits efficient retrograde targeting of projection neurons

Han

Luo

Kou

et al. 2022

Preprint

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Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.

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Fast Retrograde Access to Projection Neuron Circuits Underlying Vocal Learning in Songbirds

Cited by 27 publications

References 62 publications

Retrograde capabilities of adeno-associated virus vectors in the central nervous system

Retrograde capabilities of adeno-associated virus vectors in the central nervous system

A custom-made AAV1 variant (AAV1-T593K) enables efficient transduction of Japanese quail neurons in vitro and in vivo

AAV11 permits efficient retrograde targeting of projection neurons

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