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Viral Tracers for the Analysis of Neural Circuits

  • Chapter
Neuroanatomical Tract-Tracing 3

Abstract

Viral transneuronal tracing can be used to analyze neural circuits in the central nervous system (CNS). In particular, the pseudorabies virus (PRV) strain Bartha, an attenuated form of a pig alphaherpesvirus, is an excellent retrograde transneuronal tracer for labeling neural networks. This virus is transported from the axon terminal to the cell body of an infected neuron and enters the nucleus. There, it replicates, producing progeny virions that are distributed throughout the cytoplasm. These new viruses are then transferred into the axon terminals of second-order neurons that innervate the infected neuron, and the process is repeated. This technique has been used to analyze CNS networks involving chains of two or more functionally connected neurons. Due to the high sensitivity of viral transneuronal labeling, false-positive data can be generated, leading to potential pitfalls of interpretation—examples are discussed in this chapter. Protocols for growing PRV and viral tracing methodology are included.

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References

  • Astic, L., Saucier, D., Coulon, P., Lafay, F., and Flamand, A., 1993, The CVS strain of rabies virus as transneuronal tracer in the olfactory system of mice, Brain Res. 619(1–2):146–156.

    Article  PubMed  CAS  Google Scholar 

  • Aston-Jones, G., and Card, J. P., 2000, Use of pseudorabies virus to delineate multisynaptic circuits in brain: opportunities and limitations, J. Neurosci. Methods 103(1):51–61.

    Article  PubMed  CAS  Google Scholar 

  • Aston-Jones, G., Chen, S., Zhu, Y., and Oshinsky, M. L., 2001, A neural circuit for circadian regulation of arousal, Nat. Neurosci. 4(7):732–738.

    Article  PubMed  CAS  Google Scholar 

  • Aston-Jones, G., Zhu, Y., and Card, J. P., 2004, Numerous GABAergic afferents to locus ceruleus in the pericerulear dendritic zone: possible interneuronal pool, J. Neurosci. 24(9):2313–2321.

    Article  PubMed  CAS  Google Scholar 

  • Aujesky, A., 1902, Not readily distinguishable from rabies, with unknown origin (in Hungarian), Veteranarius 25:387–396.

    Google Scholar 

  • Babic, N., Klupp, B., Brack, A., Mettenleiter, T. C., Ugolini, G., and Flamand, A., 1996, Deletion of glycoprotein gE reduces the propagation of pseudorabies virus in the nervous system of mice after intranasal inoculation, Virology 219(1):279–284.

    Article  PubMed  CAS  Google Scholar 

  • Bak, I. J., Markham, C. H., Cook, M. L., and Stevens, J. G., 1977, Intraaxonal transport of Herpes simplex virus in the rat central nervous system, Brain Res. 136(3):415–429.

    Article  PubMed  CAS  Google Scholar 

  • Banfield, B. W., Kaufman, J. D., Randall, J. A., and Pickard, G. E., 2003, Development of pseudorabies virus strains expressing red fluorescent proteins: new tools for multisynaptic labeling applications, J. Virol. 77(18):10106–10112.

    Article  PubMed  CAS  Google Scholar 

  • Billig, I., Foris, J. M., Enquist, L. W., Card, J. P., and Yates, B. J., 2000, Definition of neuronal circuitry controlling the activity of phrenic and abdominal motoneurons in the ferret using recombinant strains of pseudorabies virus, J. Neurosci. 20(19):7446–7454.

    PubMed  CAS  Google Scholar 

  • Blessing, W. W., Li, Y. W., and Wesselingh, S. L., 1991, Transneuronal transport of herpes simplex virus from the cervical vagus to brain neurons with axonal inputs to central vagal sensory nuclei in the rat, Neuroscience 42(1):261–274.

    Article  PubMed  CAS  Google Scholar 

  • Boldogkoi, Z., Reichart, A., Toth, I. E., Sik, A., Erdelyi, F., Medveczky, I., Llorens-Cortes, C., Palkovits, M., and Lenkei, Z., 2002, Construction of recombinant pseudorabies viruses optimized for labeling and neurochemical characterization of neural circuitry, Brain Res. Mol. Brain Res. 109(1–2):105–118.

    Article  PubMed  CAS  Google Scholar 

  • Boldogkoi, Z., Sik, A., Denes, A., Reichart, A., Toldi, J., Gerendai, I., Kovacs, K. J., and Palkovits, M., 2004, Novel tracing paradigms—genetically engineered herpesviruses as tools for mapping functional circuits within the CNS: present status and future prospects, Prog. Neurobiol. 72(6):417–445.

    Article  PubMed  CAS  Google Scholar 

  • Bourgeais, L., Gauriau, C., Monconduit, L., Villanueva, L., and Bernard, J. F., 2003, Dendritic domains of nociceptive-responsive parabrachial neurons match terminal fields of lamina I neurons in the rat, J. Comp. Neurol. 464(2):238–256.

    Article  PubMed  Google Scholar 

  • Braz, J. M., Rico, B., and Basbaum, A. I., 2002, Transneuronal tracing of diverse CNS circuits by Cre-mediated induction of wheat germ agglutinin in transgenic mice, Proc. Natl. Acad. Sci. U. S. A. 99(23):15148–15153.

    Article  PubMed  CAS  Google Scholar 

  • Brideau, A. D., Card, J. P., and Enquist, L. W., 2000, Role of pseudorabies virus Us9, a type II membrane protein, in infection of tissue culture cells and the rat nervous system, J. Virol. 74(2):834–845.

    Article  PubMed  CAS  Google Scholar 

  • Broussard, D. L., Li, X., and Altschuler, S. M., 1996, Localization of GABAA alpha 1 mRNA subunit in the brainstem nuclei controlling esophageal peristalsis, Brain Res. Mol. Brain Res. 40(1):143–147.

    Article  PubMed  CAS  Google Scholar 

  • Campadelli-Fiume, G., Arsenakis, M., Farabegoli, F., and Roizman, B., 1988, Entry of herpes simplex virus 1 in BJ cells that constitutively express viral glycoprotein D is by endocytosis and results in degradation of the virus, J. Virol. 62(1):159–167.

    PubMed  CAS  Google Scholar 

  • Cano, G., Passerin, A. M., Schiltz, J. C., Card, J. P., Morrison, S. F., and Sved, A. F., 2003, Anatomical substrates for the central control of sympathetic outflow to interscapular adipose tissue during cold exposure, J. Comp. Neurol. 460(3):303–326.

    Article  PubMed  Google Scholar 

  • Card, J. P., 1998, Practical considerations for the use of pseudorabies virus in transneuronal studies of neural circuitry, Neurosci. Biobehav. Rev. 22(6):685–694.

    Article  PubMed  CAS  Google Scholar 

  • Card, J. P., 2000, Pseudorabies virus and the functional architecture of the circadian timing system, J. Biol. Rhythms 15(6):453–461.

    Article  PubMed  CAS  Google Scholar 

  • Card, J. P., Enquist, L. W., and Moore, R. Y., 1999, Neuroinvasiveness of pseudorabies virus injected intracerebrally is dependent on viral concentration and terminal field density, J. Comp. Neurol. 407(3):438–452.

    Article  PubMed  CAS  Google Scholar 

  • Card, J. P., Levitt, P., and Enquist, L. W., 1998, Different patterns of neuronal infection after intracerebral injection of two strains of pseudorabies virus, J. Virol. 72(5):4434–4441.

    PubMed  CAS  Google Scholar 

  • Card, J. P., Rinaman, L., Lynn, R. B., Lee, B. H., Meade, R. P., Miselis, R. R., and Enquist, L. W., 1993, Pseudorabies virus infection of the rat central nervous system: ultrastructural characterization of viral replication, transport, and pathogenesis, J. Neurosci. 13(6):2515–2539.

    PubMed  CAS  Google Scholar 

  • Card, J. P., Whealy, M. E., Robbins, A. K., and Enquist, L.W., 1992, Pseudorabies virus envelope glycoprotein gI influences both neurotropism and virulence during infection of the rat visual system, J. Virol. 66(5):3032–3041.

    PubMed  CAS  Google Scholar 

  • Card, J. P., Whealy, M. E., Robbins, A. K., Moore, R. Y., and Enquist, L. W., 1991, Two alpha-herpesvirus strains are transported differentially in the rodent visual system, Neuron 6(6):957–969.

    Article  PubMed  CAS  Google Scholar 

  • Carr, D. B., O’Donnell, P., Card, J. P., and Sesack, S. R., 1999, Dopamine terminals in the rat prefrontal cortex synapse on pyramidal cells that project to the nucleus accumbens, J. Neurosci. 19(24):11049–11060.

    PubMed  CAS  Google Scholar 

  • Carr, D. B. and Sesack, S. R., 2000, Dopamine terminals synapse on callosal projection neurons in the rat prefrontal cortex, J. Comp. Neurol. 425(2):275–283.

    Article  PubMed  CAS  Google Scholar 

  • Chan-Palay, V., 1976, Serotonin axons in the supra-and subependymal plexuses and in the leptomeninges; their roles in local alterations of cerebrospinal fluid and vasomotor activity, Brain Res. 102(1):103–130.

    Article  PubMed  CAS  Google Scholar 

  • Chen, S., Yang, M., Miselis, R. R., and Aston-Jones, G., 1999, Characterization of transsynaptic tracing with central application of pseudorabies virus, Brain Res. 838(1–2):171–183.

    Article  PubMed  CAS  Google Scholar 

  • Clower, D. M., West, R. A., Lynch, J. C., and Strick, P. L., 2001, The inferior parietal lobule is the target of output from the superior colliculus, hippocampus, and cerebellum, J. Neurosci. 21(16):6283–6291.

    PubMed  CAS  Google Scholar 

  • Cook, M. L. and Stevens, J. G., 1973, Pathogenesis of herpetic neuritis and ganglionitis in mice: evidence for intra-axonal transport of infection, Infect. Immun. 7(2):272–288.

    PubMed  CAS  Google Scholar 

  • DeFalco, J., Tomishima, M., Liu, H., Zhao, C., Cai, X., Marth, J. D., Enquist, L., and Friedman, J. M., 2001, Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus, Science 291(5513):2608–2613.

    Article  PubMed  CAS  Google Scholar 

  • Demmin, G. L., Clase, A. C., Randall, J. A., Enquist, L.W., and Banfield, B.W., 2001, Insertions in the gG gene of pseudorabies virus reduce expression of the upstream Us3 protein and inhibit cell-to-cell spread of virus infection, J. Virol. 75(22):10856–10869.

    Article  PubMed  CAS  Google Scholar 

  • Ding, Z. Q., Li, Y. W., Wesselingh, S. L., and Blessing, W. W., 1993, Transneuronal labelling of neurons in rabbit brain after injection of herpes simplex virus type 1 into the renal nerve, J. Auton. Nerv. Syst. 42(1):23–31.

    Article  PubMed  CAS  Google Scholar 

  • Dobbins, E. G., and Feldman, J. L., 1994, Brainstem network controlling descending drive to phrenic motoneurons in rat, J. Comp. Neurol. 347(1):64–86.

    Article  PubMed  CAS  Google Scholar 

  • Enquist, L.W., 2002, Exploiting circuit-specific spread of pseudorabies virus in the central nervous system: insights to pathogenesis and circuit tracers, J. Infect. Dis. 186(Suppl. 2):S209–S214.

    Article  PubMed  Google Scholar 

  • Enquist, L. W., Dubin, J., Whealy, M. E., and Card, J. P., 1994, Complementation analysis of pseudorabies virus gE and gI mutants in retinal ganglion cell neurotropism, J. Virol. 68(8):5275–5279.

    PubMed  CAS  Google Scholar 

  • Enquist, L. W., Tomishima, M. J., Gross, S., and Smith, G. A., 2002, Directional spread of an alpha-herpesvirus in the nervous system, Vet. Microbiol. 86(1–2):5–16.

    Article  PubMed  CAS  Google Scholar 

  • Farkas, E., Jansen, A. S., and Loewy, A. D., 1998, Periaqueductal gray matter input to cardiacrelated sympathetic premotor neurons, Brain Res. 792(2):179–192.

    Article  PubMed  CAS  Google Scholar 

  • Fukuda, J., Kurata, T., and Yamaguchi, K., 1983, Specific reduction in Na currents after infection with herpes simplex virus in cultured mammalian nerve cells, Brain Res. 268(2): 367–371.

    Article  PubMed  CAS  Google Scholar 

  • Geerling, J. C., Mettenleiter, T. C., and Loewy, A. D., 2003, Orexin neurons project to diverse sympathetic outflow systems, Neuroscience 122(2):541–550.

    Article  PubMed  CAS  Google Scholar 

  • Gerfen, C. R., O’Leary, D. D., and Cowan, W. M., 1982, A note on the transneuronal transport of wheat germ agglutinin-conjugated horseradish peroxidase in the avian and rodent visual systems, Exp. Brain Res. 48(3):443–448.

    Article  PubMed  CAS  Google Scholar 

  • Giles, M. E., Sly, D. J., McKinley, M. J., and Oldfield, B. J., 2001, A method for the identification of pseudorabies virus protein and angiotensin AT(1A) receptor mRNA expression in the same CNS neurons, Brain Res. Brain Res. Protoc. 8(3):153–158.

    Article  PubMed  CAS  Google Scholar 

  • Goodpasture, E. W., 1925, The axis-cylinders of peripheral nerves as portals of entry to the central nervous system for the virus of herpes simplex in experimentally infected rabbits, Am. J. Pathol. 1:11–33.

    Google Scholar 

  • Goodpasture, E. W., and Teague, O., 1923, Transmission of the virus of herpes fibrils along nerves in experimentally infected rabbits, J. Med. Res. 44:139–184.

    Google Scholar 

  • Graf, W., Gerrits, N., Yatim-Dhiba, N., and Ugolini, G., 2002, Mapping the oculomotor system: the power of transneuronal labelling with rabies virus, Eur. J. Neurosci. 15(9):1557–1562.

    Article  PubMed  Google Scholar 

  • Grantyn, A., Brandi, A. M., Dubayle, D., Graf, W., Ugolini, G., Hadjidimitrakis, K., and Moschovakis, A., 2002, Density gradients of trans-synaptically labeled collicular neurons after injections of rabies virus in the lateral rectus muscle of the rhesus monkey, J. Comp. Neurol. 451(4):346–361.

    Article  PubMed  Google Scholar 

  • Gustafson, D. P., 1975, Pseudorabies, In: Dunne, H. W., and Leman, A. D. (eds.), Diseases of Swine, Ames, IA: Iowa State University Press, pp. 209–223.

    Google Scholar 

  • Hannibal, J., Vrang, N., Card, J. P., and Fahrenkrug, J., 2001, Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohy-pothalamic tract, J. Biol. Rhythms 16(5):457–470.

    Article  PubMed  CAS  Google Scholar 

  • Haxhiu, M. A., Jansen, A. S., Cherniack, N. S., and Loewy, A. D., 1993, CNS innervation of airway-related parasympathetic preganglionic neurons: a transneuronal labeling study using pseudorabies virus, Brain Res. 618(1):115–134.

    Article  PubMed  CAS  Google Scholar 

  • Hoover, J. E., and Strick, P. L., 1993, Multiple output channels in the basal ganglia, Science 259(5096):819–821.

    Article  PubMed  CAS  Google Scholar 

  • Hoover, J. E., and Strick, P. L., 1999, The organization of cerebellar and basal ganglia outputs to primary motor cortex as revealed by retrograde transneuronal transport of herpes simplex virus type 1, J. Neurosci. 19(4):1446–1463.

    PubMed  CAS  Google Scholar 

  • Horowitz, L. F., Montmayeur, J. P., Echelard, Y., and Buck, L. B., 1999, A genetic approach to trace neural circuits, Proc. Natl. Acad. Sci. U. S. A. 96(6):3194–3199.

    Article  PubMed  CAS  Google Scholar 

  • Husak, P. J., Kuo, T., and Enquist, L. W., 2000, Pseudorabies virus membrane proteins gI and gE facilitate anterograde spread of infection in projection-specific neurons in the rat, J. Virol. 74(23):10975–10983.

    Article  PubMed  CAS  Google Scholar 

  • Irnaten, M., Neff, R. A., Wang, J., Loewy, A. D., Mettenleiter, T. C., and Mendelowitz, D., 2001, Activity of cardiorespiratory networks revealed by transsynaptic virus expressing GFP, J. Neurophysiol. 85(1):435–438.

    PubMed  CAS  Google Scholar 

  • Itaya, S. K., and van Hoesen, G. W., 1982, WGA-HRP as a transneuronal marker in the visual pathways of monkey and rat, Brain Res. 236(1):199–204.

    Article  PubMed  CAS  Google Scholar 

  • Jansen, A. S., Farwell, D. G., and Loewy, A. D., 1993, Specificity of pseudorabies virus as a retrograde marker of sympathetic preganglionic neurons: implications for transneuronal labeling studies, Brain Res. 617(1):103–112.

    Article  PubMed  CAS  Google Scholar 

  • Jansen, A. S., Nguyen, X. V., Karpitskiy, V., Mettenleiter, T. C., and Loewy, A. D., 1995a, Central command neurons of the sympathetic nervous system: basis of the fight-or-flight response, Science 270(5236):644–646.

    Article  PubMed  CAS  Google Scholar 

  • Jansen, A. S., Wessendorf, M. W., and Loewy, A. D., 1995b, Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion, Brain Res. 683(1):1–24.

    Article  PubMed  CAS  Google Scholar 

  • Jasmin, L., Burkey, A. R., Card, J. P., and Basbaum, A. I., 1997, Transneuronal labeling of a nociceptive pathway, the spino-(trigemino-)parabrachio-amygdaloid, in the rat, J. Neurosci. 17(10):3751–3765.

    PubMed  CAS  Google Scholar 

  • Jons, A., and Mettenleiter, T. C., 1997, Green fluorescent protein expressed by recombinant pseudorabies virus as an in vivo marker for viral replication, J. Virol. Methods 66(2):283–292.

    Article  PubMed  CAS  Google Scholar 

  • Kangrga, I. M., and Loewy, A. D., 1995, Whole-cell recordings from visualized C1 adrenergic bulbospinal neurons: ionic mechanisms underlying vasomotor tone, Brain Res. 670(2):215–232.

    Article  PubMed  CAS  Google Scholar 

  • Kaufman, G. D., Mustari, M. J., Miselis, R. R., and Perachio, A. A., 1996, Transneuronal pathways to the vestibulocerebellum, J. Comp. Neurol. 370(4):501–523.

    Article  PubMed  CAS  Google Scholar 

  • Kelly, R. M., and Strick, P. L., 2000, Rabies as a transneuronal tracer of circuits in the central nervous system, J. Neurosci. Methods 103(1):63–71.

    Article  PubMed  CAS  Google Scholar 

  • Kelly, R. M., and Strick, P. L., 2003, Cerebellar loops with motor cortex and prefrontal cortex of a nonhuman primate, J. Neurosci. 23(23):8432–8444.

    PubMed  CAS  Google Scholar 

  • Kerman, I. A., Enquist, L. W., Watson, S. J., and Yates, B. J., 2003, Brainstem substrates of sympatho-motor circuitry identified using trans-synaptic tracing with pseudorabies virus recombinants, J. Neurosci. 23(11):4657–4666.

    PubMed  CAS  Google Scholar 

  • Kim, J. S., Enquist, L.W., and Card, J. P., 1999, Circuit-specific coinfection of neurons in the rat central nervous system with two pseudorabies virus recombinants, J. Virol. 73(11):9521–9531.

    PubMed  CAS  Google Scholar 

  • Klupp, B. G., Hengartner, C. J., Mettenleiter, T. C., and Enquist, L. W., 2004, Complete, annotated sequence of the pseudorabies virus genome, J. Virol. 78(1):424–440.

    Article  PubMed  CAS  Google Scholar 

  • Kristensson, K., Lycke, E., and Sjostrand, J., 1971, Spread of herpes simplex virus in peripheral nerves, Acta Neuropathol. (Berl.) 17(1):44–53.

    Article  CAS  Google Scholar 

  • Kristensson, K., Nennesmo, L., Persson, L., and Lycke, E., 1982, Neuron to neuron transmission of herpes simplex virus. Transport of virus from skin to brainstem nuclei, J. Neurol. Sci. 54(1):149–156.

    Article  PubMed  CAS  Google Scholar 

  • Kritas, S. K., Pensaert, M. B., and Mettenleiter, T. C., 1994, Role of envelope glycoproteins gI, gp63 and gIII in the invasion and spread of Aujeszky’s disease virus in the olfactory nervous pathway of the pig, J. Gen. Virol. 75(Pt 9):2319–2327.

    PubMed  CAS  Google Scholar 

  • Krout, K. E., Mettenleiter, T. C., and Loewy, A. D., 2003, Single CNS neurons link both central motor and cardiosympathetic systems: a double-virus tracing study, Neuroscience 118(3):853–866.

    Article  PubMed  CAS  Google Scholar 

  • Kuypers, H. G., and Ugolini, G., 1990, Viruses as transneuronal tracers, Trends Neurosci. 13(2):71–75.

    Article  PubMed  CAS  Google Scholar 

  • Larsen, P. J., Enquist, L.W., and Card, J. P., 1998, Characterization of the multisynaptic neuronal control of the rat pineal gland using viral transneuronal tracing, Eur. J. Neurosci. 10(1):128–145.

    Article  PubMed  CAS  Google Scholar 

  • Levatte, M. A., Mabon, P. J., Weaver, L. C., and Dekaban, G. A., 1998, Simultaneous identification of two populations of sympathetic preganglionic neurons using recombinant herpes simplex virus type 1 expressing different reporter genes, Neuroscience 82(4):1253–1267.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y. W., Ding, Z. Q., Wesselingh, S. L., and Blessing, W. W., 1992a, Renal and adrenal sympathetic preganglionic neurons in rabbit spinal cord: tracing with herpes simplex virus, Brain Res. 573(1):147–152.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y. W., Ding, Z. Q., Wesselingh, S. L., and Blessing, W. W., 1993, Renal sympathetic preganglionic neurons demonstrated by herpes simplex virus transneuronal labelling in the rabbit: close apposition of neuropeptide Y-immunoreactive terminals, Neuroscience 53(4):1143–1152.

    Article  PubMed  CAS  Google Scholar 

  • Li, Y.W., Wesselingh, S. L., and Blessing, W.W., 1992b, Projections from rabbit caudal medulla to C1 and A5 sympathetic premotor neurons, demonstrated with phaseolus leucoagglutinin and herpes simplex virus, J. Comp. Neurol. 317(4):379–395.

    Article  PubMed  CAS  Google Scholar 

  • Loewy, A. D., and Haxhiu, M. A., 1993, CNS cell groups projecting to pancreatic parasympathetic preganglionic neurons, Brain Res. 620(2):323–330.

    Article  PubMed  CAS  Google Scholar 

  • Lomniczi, B., Blankenship, M. L., and Ben-Porat, T., 1984, Deletions in the genomes of pseudorabies virus vaccine strains and existence of four isomers of the genomes, J. Virol. 49(3):970–979.

    PubMed  CAS  Google Scholar 

  • Luppi, P. H., Aston-Jones, G., Akaoka, H., Chouvet, G., and Jouvet, M., 1995, Afferent projections to the rat locus coeruleus demonstrated by retrograde and anterograde tracing with cholera-toxin B subunit and Phaseolus vulgaris leucoagglutinin, Neuroscience 65(1):119–160.

    Article  PubMed  CAS  Google Scholar 

  • Lynch, J. C., Hoover, J. E., and Strick, P. L., 1994, Input to the primate frontal eye field from the substantia nigra, superior colliculus, and dentate nucleus demonstrated by transneuronal transport, Exp. Brain Res. 100(1):181–186.

    Article  PubMed  CAS  Google Scholar 

  • Manning, K. A., Erichsen, J. T., and Evinger, C., 1990, Retrograde transneuronal transport properties of fragment C of tetanus toxin, Neuroscience 34(1):251–263.

    Article  PubMed  CAS  Google Scholar 

  • Martin, X., and Dolivo, M., 1983, Neuronal and transneuronal tracing in the trigeminal system of the rat using the herpes virus suis, Brain Res. 273(2):253–276.

    Article  PubMed  CAS  Google Scholar 

  • Mettenleiter, T. C., 2003, Pathogenesis of neurotropic herpesviruses: role of viral glycoproteins in neuroinvasion and transneuronal spread, Virus Res. 92(2):197–206.

    Article  PubMed  CAS  Google Scholar 

  • Mettenleiter, T. C., Schreurs, C., Zuckermann, F., Ben-Porat, T., and Kaplan, A. S., 1988, Role of glycoprotein gIII of pseudorabies virus in virulence, J. Virol. 62(8):2712–2717.

    PubMed  CAS  Google Scholar 

  • Mettenleiter, T. C., Zsak, L., Kaplan, A. S., Ben-Porat, T., and Lomniczi, B., 1987, Role of a structural glycoprotein of pseudorabies in virus virulence, J. Virol. 61(12):4030–4032.

    PubMed  CAS  Google Scholar 

  • Middleton, F. A., and Strick, P. L., 1994, Anatomical evidence for cerebellar and basal ganglia involvement in higher cognitive function, Science 266(5184):458–461.

    Article  PubMed  CAS  Google Scholar 

  • Middleton, F. A., and Strick, P. L., 1996, The temporal lobe is a target of output from the basal ganglia, Proc. Natl. Acad. Sci. U.S.A. 93(16):8683–8687.

    Article  PubMed  CAS  Google Scholar 

  • Middleton, F. A., and Strick, P. L., 2001, Cerebellar projections to the prefrontal cortex of the primate, J. Neurosci. 21(2):700–712.

    PubMed  CAS  Google Scholar 

  • Middleton, F. A., and Strick, P. L., 2002, Basal-ganglia ‘projections’ to the prefrontal cortex of the primate, Cereb. Cortex 12(9):926–935.

    Article  PubMed  Google Scholar 

  • Moore, R. Y., Speh, J. C., and Card, J. P., 1995, The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells, J. Comp. Neurol. 352(3):351–366.

    Article  PubMed  CAS  Google Scholar 

  • Moschovakis, A. K., Gregoriou, G. G., Ugolini, G., Doldan, M., Graf, W., Guldin, W., Hadjidimitrakis, K., and Savaki, H. E., 2004, Oculomotor areas of the primate frontal lobes: a transneuronal transfer of rabies virus and [14C]-2-deoxyglucose functional imaging study, J. Neurosci. 24(25):5726–5740.

    Article  PubMed  CAS  Google Scholar 

  • Nichol, P. F., Chang, J. Y., Johnson, E. M., Jr., and Olivo, P. D., 1994, Infection of sympathetic and sensory neurones with herpes simplex virus does not elicit a shut-off of cellular protein synthesis: implications for viral latency and herpes vectors, Neurobiol. Dis. 1(1–2): 83–94.

    Article  PubMed  CAS  Google Scholar 

  • Norgren, R. B., Jr., and Lehman, M. N., 1998, Herpes simplex virus as a transneuronal tracer, Neurosci. Biobehav. Rev. 22(6):695–708.

    Article  PubMed  Google Scholar 

  • Norgren, R. B., Jr., McLean, J. H., Bubel, H. C., Wander, A., Bernstein, D. I., and Lehman, M. N., 1992, Anterograde transport of HSV-1 and HSV-2 in the visual system, Brain Res. Bull. 28(3):393–399.

    Article  PubMed  Google Scholar 

  • O’Donnell, P., Lavin, A., Enquist, L. W., Grace, A. A., and Card, J. P., 1997, Interconnected parallel circuits between rat nucleus accumbens and thalamus revealed by retrograde transsynaptic transport of pseudorabies virus, J. Neurosci. 17(6):2143–2167.

    PubMed  CAS  Google Scholar 

  • Oldfield, B. J., Giles, M. E., Watson, A., Anderson, C., Colvill, L. M., and McKinley, M. J., 2002, The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat, Neuroscience 110(3):515–526.

    Article  PubMed  CAS  Google Scholar 

  • Pickard, G. E., Smeraski, C. A., Tomlinson, C. C., Banfield, B. W., Kaufman, J., Wilcox, C. L., Enquist, L. W., and Sollars, P. J., 2002, Intravitreal injection of the attenuated pseudorabies virus PRV Bartha results in infection of the hamster suprachiasmatic nucleus only by retrograde transsynaptic transport via autonomic circuits, J. Neurosci. 22(7): 2701–2710.

    PubMed  CAS  Google Scholar 

  • Ricardo, J. A., and Koh, E. T., 1978, Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat, Brain Res. 153(1):1–26.

    Article  PubMed  CAS  Google Scholar 

  • Rinaman, L., Card, J. P., and Enquist, L.W., 1993, Spatiotemporal responses of astrocytes, ramified microglia, and brain macrophages to central neuronal infection with pseudorabies virus, J. Neurosci. 13(2):685–702.

    PubMed  CAS  Google Scholar 

  • Rinaman, L., and Schwartz, G., 2004, Anterograde transneuronal viral tracing of central viscerosensory pathways in rats, J. Neurosci. 24(11):2782–2786.

    Article  PubMed  CAS  Google Scholar 

  • Rotto-Percelay, D. M., Wheeler, J. G., Osorio, F. A., Platt, K. B., and Loewy, A. D., 1992, Transneuronal labeling of spinal interneurons and sympathetic preganglionic neurons after pseudorabies virus injections in the rat medial gastrocnemius muscle, Brain Res. 574(1–2):291–306.

    Article  PubMed  CAS  Google Scholar 

  • Rouiller, E. M., Capt, M., Dolivo, M., and De Ribaupierre, F., 1986, Tensor tympani reflex pathways studied with retrograde horseradish peroxidase and transneuronal viral tracing techniques, Neurosci. Lett. 72(3):247–252.

    Article  PubMed  CAS  Google Scholar 

  • Rouiller, E. M., Capt, M., Dolivo, M., and De Ribaupierre, F., 1989, Neuronal organization of the stapedius reflex pathways in the rat: a retrograde HRP and viral transneuronal tracing study, Brain Res. 476(1):21–28.

    Article  PubMed  CAS  Google Scholar 

  • Sabin, A. B., 1938, Progression of different nasally instilled viruses along different nervous pathways in the same host, Proc. Soc. Exp. Biol. 38:270–275.

    Google Scholar 

  • Sams, J. M., Jansen, A. S., Mettenleiter, T. C., and Loewy, A. D., 1995, Pseudorabies virus mutants as transneuronal markers, Brain Res. 687(1–2):182–190.

    Article  PubMed  CAS  Google Scholar 

  • Smeraski, C. A., Sollars, P. J., Ogilvie, M. D., Enquist, L.W., and Pickard, G. E., 2004, Suprachiasmatic nucleus input to autonomic circuits identified by retrograde transsynaptic transport of pseudorabies virus from the eye, J. Comp. Neurol. 471(3):298–313.

    Article  PubMed  Google Scholar 

  • Smiley, J. R., 2004, Herpes simplex virus virion host shutoff protein: immune evasion mediated by a viral Rnase? J. Virol. 78(3):1063–1068.

    Article  PubMed  CAS  Google Scholar 

  • Smith, B. N., Banfield, B. W., Smeraski, C. A., Wilcox, C. L., Dudek, F. E., Enquist, L. W., and Pickard, G. E., 2000, Pseudorabies virus expressing enhanced green fluorescent protein: a tool for in vitro electrophysiological analysis of transsynaptically labeled neurons in identified central nervous system circuits, Proc. Natl. Acad. Sci. U. S. A. 97(16):9264–9269.

    Article  PubMed  CAS  Google Scholar 

  • Song, C. K., and Bartness, T. J., 2001, CNS sympathetic outflow neurons to white fat that express MEL receptors may mediate seasonal adiposity, Am. J. Physiol. Regul. Integr. Comp. Physiol. 281(2):R666–R672.

    PubMed  CAS  Google Scholar 

  • Stornetta, R. L., McQuiston, T. J., and Guyenet, P. G., 2004, GABAergic and glycinergic presympathetic neurons of rat medulla oblongata identified by retrograde transport of pseudorabies virus and in situ hybridization, J. Comp. Neurol. 479(3):257–270.

    Article  PubMed  CAS  Google Scholar 

  • Strack, A. M., and Loewy, A. D., 1990, Pseudorabies virus: a highly specific transneuronal cell body marker in the sympathetic nervous system, J. Neurosci. 10(7):2139–2147.

    PubMed  CAS  Google Scholar 

  • Strack, A. M., Sawyer, W. B., Hughes, J. H., Platt, K. B., and Loewy, A. D., 1989a, A general pattern of CNS innervation of the sympathetic outflow demonstrated by transneuronal pseudorabies viral infections, Brain Res. 491(1):156–162.

    Article  PubMed  CAS  Google Scholar 

  • Strack, A. M., Sawyer, W. B., Platt, K. B., and Loewy, A. D., 1989b, CNS cell groups regulating the sympathetic outflow to adrenal gland as revealed by transneuronal cell body labeling with pseudorabies virus, Brain Res. 491(2):274–296.

    Article  PubMed  CAS  Google Scholar 

  • Sylvester, C. M., Krout, K. E., and Loewy, A. D., 2002, Suprachiasmatic nucleus projection to the medial prefrontal cortex: a viral transneuronal tracing study, Neuroscience 114(4):1071–1080.

    PubMed  CAS  Google Scholar 

  • Tang, Y., Rampin, O., Giuliano, F., and Ugolini, G., 1999, Spinal and brain circuits to motoneurons of the bulbospongiosus muscle: retrograde transneuronal tracing with rabies virus, J. Comp. Neurol. 414(2):167–192.

    Article  PubMed  CAS  Google Scholar 

  • Ter Horst, G. J., 2000, Transneuronal retrograde dual viral labelling of central autonomic circuitry: possibilities and pitfalls, Auton. Neurosci. 83(3):134–139.

    Article  PubMed  Google Scholar 

  • Ter Horst, G. J., Hautvast, R.W., De Jongste, M. J., and Korf, J., 1996, Neuroanatomy of cardiac activity-regulating circuitry: a transneuronal retrograde viral labelling study in the rat, Eur. J. Neurosci. 8(10):2029–2041.

    Article  PubMed  Google Scholar 

  • Tomishima, M. J., and Enquist, L. W., 2001, A conserved alpha-herpesvirus protein necessary for axonal localization of viral membrane proteins, J. Cell Biol. 154(4):741–752.

    Article  PubMed  CAS  Google Scholar 

  • Tomishima, M. J., Smith, G. A., and Enquist, L. W., 2001, Sorting and transport of alpha herpesviruses in axons, Traffic 2(7):429–436.

    Article  PubMed  CAS  Google Scholar 

  • Ueyama, T., Krout, K. E., Nguyen, X. V., Karpitskiy, V., Kollert, A., Mettenleiter, T. C., and Loewy, A. D., 1999, Suprachiasmatic nucleus: a central autonomic clock, Nat. Neurosci. 2(12):1051–1053.

    Article  PubMed  CAS  Google Scholar 

  • Ugolini, G., 1995, Specificity of rabies virus as a transneuronal tracer of motor networks: transfer from hypoglossal motoneurons to connected second-order and higher order central nervous system cell groups, J. Comp. Neurol. 356(3):457–480.

    Article  PubMed  CAS  Google Scholar 

  • Ugolini, G., Kuypers, H. G., and Simmons, A., 1987, Retrograde transneuronal transfer of herpes simplex virus type 1 (HSV 1) from motoneurones, Brain Res. 422(2):242–256.

    Article  PubMed  CAS  Google Scholar 

  • Ugolini, G., Kuypers, H. G., and Strick, P. L., 1989, Transneuronal transfer of herpes virus from peripheral nerves to cortex and brainstem, Science 243(4887):89–91.

    Article  PubMed  CAS  Google Scholar 

  • Vahlne, A., Nystrom, B., Sandberg, M., Hamberger, A., and Lycke, E., 1978, Attachment of herpes simplex virus to neurons and glial cells, J. Gen. Virol. 40(2):359–371.

    Article  PubMed  CAS  Google Scholar 

  • Wesselingh, S. L., Li, Y. W., and Blessing, W. W., 1989, PNMT-containing neurons in the rostral medulla oblongata (C1, C3 groups) are transneuronally labelled after injection of herpes simplex virus type 1 into the adrenal gland, Neurosci. Lett. 106(1–2):99–104.

    Article  PubMed  CAS  Google Scholar 

  • Westerhaus, M. J., and Loewy, A. D., 1999, Sympathetic-related neurons in the preoptic region of the rat identified by viral transneuronal labeling, J. Comp. Neurol. 414(3):361–378.

    Article  PubMed  CAS  Google Scholar 

  • Westerhaus, M. J., and Loewy, A. D., 2001, Central representation of the sympathetic nervous system in the cerebral cortex, Brain Res. 903(1–2):117–127.

    Article  PubMed  CAS  Google Scholar 

  • Whealy, M. E., Card, J. P., Robbins, A. K., Dubin, J. R., Rziha, H. J., and Enquist, L. W., 1993, Specific pseudorabies virus infection of the rat visual system requires both gI and gp63 glycoproteins, J. Virol. 67(7):3786–3797.

    PubMed  CAS  Google Scholar 

  • Wiesel, T. N., Hubel, D. H., and Lam, D. M., 1974, Autoradiographic demonstration of oculardominance columns in the monkey striate cortex by means of transneuronal transport, Brain Res. 79(2):273–279.

    Article  PubMed  CAS  Google Scholar 

  • Zemanick, M. C., Strick, P. L., and Dix, R. D., 1991, Direction of transneuronal transport of herpes simplex virus 1 in the primate motor system is strain-dependent, Proc. Natl. Acad. Sci. U.S.A. 88(18):8048–8051.

    Article  PubMed  CAS  Google Scholar 

  • Zou, Z., Horowitz, L. F., Montmayeur, J. P., Snapper, S., and Buck, L. B., 2001, Genetic tracing reveals a stereotyped sensory map in the olfactory cortex, Nature 414(6860):173–179.

    Article  PubMed  CAS  Google Scholar 

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Geerling, J.C., Mettenleiter, T.C., Loewy, A.D. (2006). Viral Tracers for the Analysis of Neural Circuits. In: Zaborszky, L., Wouterlood, F.G., Lanciego, J.L. (eds) Neuroanatomical Tract-Tracing 3. Springer, Boston, MA . https://doi.org/10.1007/0-387-28942-9_9

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