Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2017

Open Access 01-12-2017 | Methodology

Anterograde monosynaptic transneuronal tracers derived from herpes simplex virus 1 strain H129

Authors: Wen-Bo Zeng, Hai-Fei Jiang, Ya-Dong Gang, Yi-Ge Song, Zhang-Zhou Shen, Hong Yang, Xiao Dong, Yong-Lu Tian, Rong-Jun Ni, Yaping Liu, Na Tang, Xinyan Li, Xuan Jiang, Ding Gao, Michelle Androulakis, Xiao-Bin He, Hui-Min Xia, Ying-Zi Ming, Youming Lu, Jiang-Ning Zhou, Chen Zhang, Xue-Shan Xia, Yousheng Shu, Shao-Qun Zeng, Fuqiang Xu, Fei Zhao, Min-Hua Luo

Published in: Molecular Neurodegeneration | Issue 1/2017

Login to get access

Abstract

Background

Herpes simplex virus type 1 strain 129 (H129) has represented a promising anterograde neuronal circuit tracing tool, which complements the existing retrograde tracers. However, the current H129 derived tracers are multisynaptic, neither bright enough to label the details of neurons nor capable of determining direct projection targets as monosynaptic tracer.

Methods

Based on the bacterial artificial chromosome of H129, we have generated a serial of recombinant viruses for neuronal circuit tracing. Among them, H129-G4 was obtained by inserting binary tandemly connected GFP cassettes into the H129 genome, and H129-ΔTK-tdT was obtained by deleting the thymidine kinase (TK) gene and adding tdTomato coding gene to the H129 genome. Then the obtained viral tracers were tested in vitro and in vivo for the tracing capacity.

Results

H129-G4 is capable of transmitting through multiple synapses, labeling the neurons by green florescent protein, and visualizing the morphological details of the labeled neurons. H129-ΔTK-tdT neither replicates nor spreads in neurons alone, but transmits to and labels the postsynaptic neurons with tdTomato in the presence of complementary expressed TK from a helper virus. H129-ΔTK-tdT is also capable to map the direct projectome of the specific neuron type in the given brain regions in Cre transgenic mice. In the tested brain regions where circuits are well known, the H129-ΔTK-tdT tracing patterns are consistent with the previous results.

Conclusions

With the assistance of the helper virus complimentarily expressing TK, H129-ΔTK-tdT replicates in the initially infected neuron, transmits anterogradely through one synapse, and labeled the postsynaptic neurons with tdTomato. The H129-ΔTK-tdT anterograde monosynaptic tracing system offers a useful tool for mapping the direct output in neuronal circuitry. H129-G4 is an anterograde multisynaptic tracer with a labeling signal strong enough to display the details of neuron morphology.
Appendix
Available only for authorised users
Literature
1.
2.
Wojaczynski GJ, Engel EA, Steren KE, Enquist LW, Patrick Card J. The neuroinvasive profiles of H129 (herpes simplex virus type 1) recombinants with putative anterograde-only transneuronal spread properties. Brain Struct Funct. 2015;220:1395–420.CrossRefPubMed
3.
McGovern AE, Driessen AK, Simmons DG, Powell J, Davis-Poynter N, Farrell MJ, Mazzone SB. Distinct brainstem and forebrain circuits receiving tracheal sensory neuron inputs revealed using a novel conditional anterograde transsynaptic viral tracing system. J Neurosci. 2015;35:7041–55.CrossRefPubMed
4.
Zemanick MC, Strick PL, Dix RD. Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent. Proc Natl Acad Sci U S A. 1991;88:8048–51.CrossRefPubMedPubMedCentral
5.
LaVail JH, Topp KS, Giblin PA, Garner JA. Factors that contribute to the transneuronal spread of herpes simplex virus. J Neurosci Res. 1997;49:485–96.CrossRefPubMed
6.
Sun N, Cassell MD, Perlman S. Anterograde, transneuronal transport of herpes simplex virus type 1 strain H129 in the murine visual system. J Virol. 1996;70:5405–13.PubMedPubMedCentral
7.
Barnett EM, Evans GD, Sun N, Perlman S, Cassell MD. Anterograde tracing of trigeminal afferent pathways from the murine tooth pulp to cortex using herpes simplex virus type 1. J Neurosci. 1995;15:2972–84.PubMed
8.
Rinaman L, Schwartz G. Anterograde transneuronal viral tracing of central viscerosensory pathways in rats. J Neurosci. 2004;24:2782–6.CrossRefPubMed
9.
Kelly RM, Strick PL. Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate. J Neurosci. 2003;23:8432–44.PubMed
10.
Archin NM, Atherton SS. Rapid spread of a neurovirulent strain of HSV-1 through the CNS of BALB/c mice following anterior chamber inoculation. J Neuro-Oncol. 2002;8:122–35.
11.
Lo L, Anderson DJ. A Cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons. Neuron. 2011;72:938–50.CrossRefPubMedPubMedCentral
12.
McGovern AE, Davis-Poynter N, Rakoczy J, Phipps S, Simmons DG, Mazzone SB. Anterograde neuronal circuit tracing using a genetically modified herpes simplex virus expressing EGFP. J Neurosci Methods. 2012;209:158–67.CrossRefPubMed
13.
Beier KT, Mundell NA, Pan YA, Cepko CL: Anterograde or Retrograde Transsynaptic Circuit Tracing in Vertebrates with Vesicular Stomatitis Virus Vectors. Curr Protoc Neurosci. 2016;74:1 26 21–27.
14.
Beier KT, Saunders A, Oldenburg IA, Miyamichi K, Akhtar N, Luo L, Whelan SP, Sabatini B, Cepko CL. Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors. Proc Natl Acad Sci U S A. 2011;108:15414–9.CrossRefPubMedPubMedCentral
15.
Quan T, Zhou H, Li J, Li S, Li A, Li Y, Lv X, Luo Q, Gong H, Zeng S. NeuroGPS-tree: automatic reconstruction of large-scale neuronal populations with dense neurites. Nat Methods. 2016;13:51–4.PubMed
16.
Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, et al. Genome of the Chinese tree shrew. Nat Commun. 2013;4:1426.CrossRefPubMed
17.
Li L, Li Z, Wang E, Yang R, Xiao Y, Han H, Lang F, Li X, Xia Y, Gao F, et al. Herpes simplex virus 1 infection of tree shrews differs from that of mice in the severity of acute infection and viral transcription in the peripheral nervous system. J Virol. 2015;90:790–804.CrossRefPubMedPubMedCentral
18.
Taylor AM, Blurton-Jones M, Rhee SW, Cribbs DH, Cotman CW, Jeon NL. A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods. 2005;2:599–605.CrossRefPubMedPubMedCentral
19.
Katz LC, Crowley JC. Development of cortical circuits: lessons from ocular dominance columns. Nat Rev Neurosci. 2002;3:34–42.CrossRefPubMed
20.
21.
Viaene AN, Petrof I, Sherman SM. Synaptic properties of thalamic input to the subgranular layers of primary somatosensory and auditory cortices in the mouse. J Neurosci. 2011;31:12738–47.CrossRefPubMedPubMedCentral
22.
Viaene AN, Petrof I, Sherman SM. Synaptic properties of thalamic input to layers 2/3 and 4 of primary somatosensory and auditory cortices. J Neurophysiol. 2011;105:279–92.CrossRefPubMed
23.
Viaene AN, Petrof I, Sherman SM. Properties of the thalamic projection from the posterior medial nucleus to primary and secondary somatosensory cortices in the mouse. Proc Natl Acad Sci U S A. 2011;108:18156–61.CrossRefPubMedPubMedCentral
24.
Weir JP. Infection of human NT2 cells and differentiated NT-neurons with herpes simplex virus and replication-incompetent herpes simplex virus vectors. J Neuro-Oncol. 2001;7:43–51.
25.
de Castro F. Wiring olfaction: the cellular and molecular mechanisms that guide the development of synaptic connections from the nose to the cortex. Front Neurosci. 2009;3:52.PubMedPubMedCentral
26.
Martinez-Marcos A. On the organization of olfactory and vomeronasal cortices. Prog Neurobiol. 2009;87:21–30.CrossRefPubMed
27.
Lee Y, Messing A, Su M, Brenner M. GFAP promoter elements required for region-specific and astrocyte-specific expression. Glia. 2008;56:481–93.CrossRefPubMed
28.
Saunders A, Johnson CA, Sabatini BL. Novel recombinant adeno-associated viruses for Cre activated and inactivated transgene expression in neurons. Front Neural Circuits. 2012;6:47.CrossRefPubMedPubMedCentral
29.
Cowan RL, Wilson CJ, Emson PC, Heizmann CW. Parvalbumin-containing GABAergic interneurons in the rat neostriatum. J Comp Neurol. 1990;302:197–205.CrossRefPubMed
30.
Halassa MM, Siegle JH, Ritt JT, Ting JT, Feng G, Moore CI. Selective optical drive of thalamic reticular nucleus generates thalamic bursts and cortical spindles. Nat Neurosci. 2011;14:1118–20.CrossRefPubMedPubMedCentral
31.
Kuan L, Li Y, Lau C, Feng D, Bernard A, Sunkin SM, Zeng H, Dang C, Hawrylycz M, Ng L. Neuroinformatics of the Allen mouse brain connectivity atlas. Methods. 2015;73:4–17.CrossRefPubMed
32.
Rosen ZB, Cheung S, Siegelbaum SA. Midbrain dopamine neurons bidirectionally regulate CA3-CA1 synaptic drive. Nat Neurosci. 2015;18:1763–71.CrossRefPubMed
33.
34.
Munch-Petersen B. Enzymatic regulation of cytosolic thymidine kinase 1 and mitochondrial thymidine kinase 2: a mini review. Nucleosides Nucleotides Nucleic Acids. 2010;29:363–9.CrossRefPubMed
35.
Song CK, Schwartz GJ, Bartness TJ. Anterograde transneuronal viral tract tracing reveals central sensory circuits from white adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2009;296:R501–11.CrossRefPubMed
36.
Kennedy PG, Al-Saadi SA, Clements GB. Reactivation of latent herpes simplex virus from dissociated identified dorsal root ganglion cells in culture. J Gen Virol. 1983;64(Pt 7):1629–35.CrossRefPubMed
37.
Callaway EM. Transneuronal circuit tracing with neurotropic viruses. Curr Opin Neurobiol. 2008;18:617–23.CrossRefPubMed
38.
39.
Seibenhener ML, Wooten MW. Isolation and culture of hippocampal neurons from prenatal mice. J Vis Exp. 2012.
40.
Park JW, Vahidi B, Taylor AM, Rhee SW, Jeon NL. Microfluidic culture platform for neuroscience research. Nat Protoc. 2006;1:2128–36.CrossRefPubMed
41.
Meberg PJ, Miller MW. Culturing hippocampal and cortical neurons. Methods Cell Biol. 2003;71:111–27.CrossRefPubMed
42.
Malin SA, Davis BM, Molliver DC. Production of dissociated sensory neuron cultures and considerations for their use in studying neuronal function and plasticity. Nat Protoc. 2007;2:152–60.CrossRefPubMed
43.
Zhao F, Shen ZZ, Liu ZY, Zeng WB, Cheng S, Ma YP, Rayner S, Yang B, Qiao GH, Jiang HF, et al. Identification and BAC construction of Han, the first characterized HCMV clinical strain in China. J Med Virol. 2015.
44.
Yu D, Smith GA, Enquist LW, Shenk T. Construction of a self-excisable bacterial artificial chromosome containing the human cytomegalovirus genome and mutagenesis of the diploid TRL/IRL13 gene. J Virol. 2002;76:2316–28.CrossRefPubMedPubMedCentral
45.
Zheng T, Yang Z, Li A, Lv X, Zhou Z, Wang X, Qi X, Li S, Luo Q, Gong H, Zeng S. Visualization of brain circuits using two-photon fluorescence micro-optical sectioning tomography. Opt Express. 2013;21:9839–50.CrossRefPubMed
46.
Xiong HQ, Zhou ZQ, Zhu MQ, Lv XH, Li AA, Li SW, Li LH, Yang T, Wang SM, Yang ZQ, et al. Chemical reactivation of quenched fluorescent protein molecules enables resin-embedded fluorescence microimaging. Nat Commun. 2014;5
47.
Gong H, Zeng SQ, Yan C, Lv XH, Yang ZQ, Xu TH, Feng Z, Ding WX, Qi XL, Li AA, et al. Continuously tracing brain-wide long-distance axonal projections in mice at a one-micron voxel resolution. NeuroImage. 2013;74:87–98.CrossRefPubMed
48.
Harris J, Lee H, Vahidi B, Tu C, Cribbs D, Jeon NL, Cotman C. Fabrication of a Microfluidic Device for the Compartmentalization of Neuron Soma and Axons. JoVE. 2007;261:e261.
49.
Paxinos G, Franklin KBJ. The mouse brain in Stereotaxic coordinates. Elsevier Academic Press; 2004.
Metadata
Title
Anterograde monosynaptic transneuronal tracers derived from herpes simplex virus 1 strain H129
Authors
Wen-Bo Zeng
Hai-Fei Jiang
Ya-Dong Gang
Yi-Ge Song
Zhang-Zhou Shen
Hong Yang
Xiao Dong
Yong-Lu Tian
Rong-Jun Ni
Yaping Liu
Na Tang
Xinyan Li
Xuan Jiang
Ding Gao
Michelle Androulakis
Xiao-Bin He
Hui-Min Xia
Ying-Zi Ming
Youming Lu
Jiang-Ning Zhou
Chen Zhang
Xue-Shan Xia
Yousheng Shu
Shao-Qun Zeng
Fuqiang Xu
Fei Zhao
Min-Hua Luo
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2017
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-017-0179-7

Other articles of this Issue 1/2017

Molecular Neurodegeneration 1/2017 Go to the issue

Research article

Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency

Research article

Together JUN and DDIT3 (CHOP) control retinal ganglion cell death after axonal injury

Erratum

Erratum to: Glymphatic distribution of CSF-derived apoE into brain is isoform specific and suppressed during sleep deprivation

Review

Iron regulatory protein (IRP)-iron responsive element (IRE) signaling pathway in human neurodegenerative diseases

Commentary

Diurnal oscillation of CSF Aβ and other AD biomarkers

Review

Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk