Neuronal Network Dissection with Neurotropic Virus Tracing

Rao, Xiaoping; Wang, Jie

doi:10.1007/s12264-020-00472-z

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…AAVs are useful vectors for therapeutic purpose by delivering genes and drug and for functional studies (Haggerty et al, 2020 ). Although they were used in some studies as neuronal tracers (Wouterlood et al, 2014 ; Rao and Wang, 2020 ; Luchicchi et al, 2021 ) and local injection in the mouse brain revealed Golgi-like detail (Watakabe et al, 2014 ; Lin et al, 2018 ), our data demonstrated that systemically administered AAVs do not have the capacity to define fine morphological profiling of enteric nervous system. In addition, many enteric neurons did not contain AAV in their processes and AAV transduction weakened immunolabeling neurons and nerve fibers, which is an obstacle to characterize the neurochemistry.…”

Section: Discussionmentioning

confidence: 61%

Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice

et al. 2022

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Systemic delivery of adeno-associated virus (AAV) vectors transduces the enteric nervous system. However, less is known on the mapping and morphological and neurochemical characterization in the adult mouse colon. We used AAV9-CAG-GFP (AAV9) and AAV-PHP.S-hSyn1-tdTomato farnesylated (PHP.S-tdTf) to investigate the segmental distribution, morphologies and neurochemical coding of the transduction. The vectors were retro-orbitally injected in male and female adult mice, and 3 weeks later, the colon was prepared for microcopy with or without immunohistochemistry for neuronal and non-neuronal markers. In contrast to the distributions in neonatal and juvenile rodents, the AAV transduction in neurons and/or nerve fibers was the highest in the proximal colon, decreased gradually in the transverse, and was sparse in the distal colon without difference between sexes. In the proximal colon, the AAV9-transduced myenteric neurons were unevenly distributed. The majority of enteric neurons did not have AAV9 expression in their processes, except those with big soma with or without variously shaped dendrites, and a long axon. Immunolabeling demonstrated that about 31% neurons were transduced by AAV9, and the transduction was in 50, 28, and 31% of cholinergic, nitrergic, and calbindin-positive myenteric neurons, respectively. The nerve fiber markers, calcitonin gene-related peptide alpha, tyrosine hydroxylase or vasoactive intestinal polypeptide co-localized with AAV9 or PHP.S-tdTf in the mucosa, and rarely in the myenteric plexus. Unexpectedly, AAV9 expression appeared also in a few c-Kit immunoreactive cells among the heavily populated interstitial cells of Cajal (ICC). In the distal colon, the AAV transduction appeared in a few nerve fibers mostly the interganglionic strands. Other types of AAV9 and AAV-PHP vectors induced a similar colonic segmental difference which is not colon specific since neurons were transduced in the small intestine and gastric antrum, while little in the gastric corpus and none in the lower esophagus.ConclusionThese findings demonstrate that in adult mice colon that there is a rostro-caudal decrease in the transduction of systemic delivery of AAV9 and its variants independent of sex. The characterization of AAV transduction in the proximal colon in cholinergic and nitrergic myenteric neurons along with a few ICC suggests implications in circuitries regulating motility.

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Section: Discussionmentioning

confidence: 61%

Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice

et al. 2022

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“…To discover the complex connection of neural circuits, neurotropic viruses provide new access to trace neural circuits. Neurotropic viruses are a series of viral vectors that can infect neurons and propagate along neural circuits and synapses [7]. Compared with traditional neural circuit-tracing methods, neurotropic viruses can not only transmit across synapses without any signal attenuation but also control the anterograde or retrograde direction of trans-synaptic transmission and also are compatible with many genetic markers [8].…”

Section: Virus Tracingmentioning

confidence: 99%

The influence of the nervous system on social behavior

Jin

2023

TNS

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Social behavior plays an essential role in our daily life, not only in humans but also in other species, contacting with others through sociability can help organisms to contact with comrades and distinguish surrounding environments to survive well in different situations. This paper will focus on some techniques that are used widely in detecting neurons and the role of the nervous system in conducting animals' social behavior through mouse models to provide new ideas for the treatment of social disorders.

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“…Numerous virus vectors were constructed to dissect the structure of neural networks after genetic modifications, such as herpes simplex virus (HSV), pseudorabies virus (PRV), rabies virus (RV), etc. (Nassi, Cepko, Born, & Beier, 2015; Rao & Wang, 2020; Ugolini, 2010). However, most of them can only be used for ex vivo imaging due to their virulence.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal neural connection detection using a ferritin‐encoding adeno‐associated virus vector and in vivo MRI method

Cai

Zheng

Thompson

et al. 2021

Human Brain Mapping

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The investigation of neural circuits is important for interpreting both healthy brain function and psychiatric disorders. Currently, the architecture of neural circuits is always investigated with fluorescent protein encoding neurotropic virus and ex vivo fluorescent imaging technology. However, it is difficult to obtain a whole-brain neural circuit connection in living animals, due to the limited fluorescent imaging depth.Herein, the noninvasive, whole-brain imaging technique of MRI and the hypotoxicity virus vector AAV (adeno-associated virus) were combined to investigate the wholebrain neural circuits in vivo. AAV2-retro are an artificially-evolved virus vector that permits access to the terminal of neurons and retrograde transport to their cell bodies. By expressing the ferritin protein which could accumulate iron ions and influence the MRI contrast, the neurotropic virus can cause MRI signal changes in the infected regions. For mice injected with the ferritin-encoding virus vector (rAAV2-retro-CAG-Aoling Cai and Ning Zheng contributed equally to this work.

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Neuronal Network Dissection with Neurotropic Virus Tracing

Cited by 6 publications

References 9 publications

Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice

Transduction of Systemically Administered Adeno-Associated Virus in the Colonic Enteric Nervous System and c-Kit Cells of Adult Mice

The influence of the nervous system on social behavior

Longitudinal neural connection detection using a ferritin‐encoding adeno‐associated virus vector and in vivo MRI method

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