Skip to main content
SpringerLink
Log in

Neurotrophic regulation of the development and function of the neuromuscular synapses

  • Published:
Journal of Neurocytology

Abstract

Recent studies have established that one of the major functions of neurotrophic factors is to regulate synaptic development and plasticity. This owes a great deal to the studies using the neuromuscular junction (NMJ) as a model system. In this review, we summarize the effects of various neurotrophic factors on the development and function of the neuromuscular synapses. We describe experiments addressing the role of neurotrophins, as well as that of other factors (GFLs, TGF-βs, and Wnts). The synaptic effects of neurotrophic factors are divided into two categories: acute effects on synaptic transmission and plasticity occurring within seconds or minutes after cells are exposed to a particular factor, and long-term regulation of synaptic structure and function that takes days to accomplish. We consider the presynaptic effects on the release of the neurotransmitter ACh, as well as the postsynaptic effects on the clustering of ACh receptors. Further studies of the mechanisms underlying these regulatory effects will help us better understand how neurotrophic factors can achieve diverse and synapse-specific modulation in the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • AAKALU, G., SMITH, W. B., NGUYEN, N., JIANG, C. & SCHUMAN, E. M. (2001) Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30, 48–502.

    PubMed  Google Scholar 

  • ABERLE, H., HAGHIGHI, A. P., FETTER, R. D., MCCABE, B. D., MAGALHAES, T. R. & GOODMAN, C. S. (2002) Wishful thinking encodes a BMP type II receptor that regulates synaptic growth in Drosophila. Neuron 33, 54–558.

    PubMed  Google Scholar 

  • AIRAKSINEN, M. S., TITIEVSKY, A. & SAARMA, M. (1999a) GDNFfamily neurotrophic factor signaling: Four masters, one servant? Mol. Cell. Neurosci. 13, 31–325.

    PubMed  Google Scholar 

  • AIRAKSINEN, M. S., TITIEVSKY, A. & SAARMA, M. (1999b) GDNFfamily neurotrophic factor signaling: Four masters, one servant? Mol. Cell. Neurosci. 13, 31–325.

    PubMed  Google Scholar 

  • AIRAKSINEN, M. S. & SAARMA, M. (2002) The GDNF family: Signalling, biological functions and therapeutic value. Nat. Rev. Neurosci. 3, 38–394.

    PubMed  Google Scholar 

  • ARCE, V., POLLOCK, R. A., PHILIPPE, J. M., PENNICA, D., HENDERSON, C. E. & DELAPEYRIERE, O. (1998) Synergistic effects of schwann-and muscle-derived factors on motoneuron survival involve GDNF and cardiotrophin-1 (CT-1). J. Neurosci. 18, 144–1448.

    PubMed  Google Scholar 

  • ATTISANO, L. & WRANA, J. L. (2002) Signal transduction by the TGF-beta superfamily. Science 296, 164–1647.

    PubMed  Google Scholar 

  • BALDELLI, P., MAGNELLI, V. & CARBONE, E. (1999) Selective up-regulation of P-and R-type Ca2+ channels in rat embryo motoneurons by BDNF. Eur. J. Neurosci. 11, 112–1133.

    PubMed  Google Scholar 

  • BALOH, R. H., ENOMOTO, H., JOHNSON, E. M., JR. & MILBRANDT, J. (2000) The GDNF family ligands and receptors—Implications for neural development. Curr. Opin. Neurobiol. 10, 10–110.

    PubMed  Google Scholar 

  • BARBACID, M. (1994) The Trk family of neurotrophin receptors. J. Neurobiol. 25, 138–1403.

    PubMed  Google Scholar 

  • BELLUARDO, N., WESTERBLAD, H., MUDO, G., CASABONA, A., BRUTON, J., CANIGLIA, G., PASTORIS, O., GRASSI, F. & IBANEZ, C. F. (2001) Neuromuscular junction disassembly and muscle fatigue in mice lacking neurotrophin-4. Mol. Cell Neurosci. 18, 5–67.

    PubMed  Google Scholar 

  • BILAK, M. M., SHIFRIN, D. A., CORSE, A. M., BILAK, S. R. & KUNCL, R. W. (1999) Neuroprotective utility and neurotrophic action of neurturin in postnatal motor neurons: Comparison with GDNF and persephin. Mol. Cell Neurosci. 13, 32–336.

    PubMed  Google Scholar 

  • BOTHWELL, M. (1995) Functional interactions of neurotrophins and neurotrophin receptors. Annu. Rev. Neurosci. 18, 22–253.

    PubMed  Google Scholar 

  • BOULANGER, L. & POO, M. M. (1999a) Presynaptic depolarization facilitates neurotrophin-induced synaptic potentiation. Nat. Neurosci. 2, 34–351.

    PubMed  Google Scholar 

  • BOULANGER, L. & POO, M. M. (1999b) Gating of BDNFinduced synaptic potentiation by cAMP. Science 284, 198–1984.

    PubMed  Google Scholar 

  • CHANG, S. & POPOV, S. V. (1999) Long-range signaling within growing neurites mediated by neurotrophin-3. Proc. Natl. Acad. Sci. USA 96, 409–4100.

    PubMed  Google Scholar 

  • CHAO, M. V. (1994) The p75 neurotrophin receptor. J. Neurobiol. 25, 137–1385.

    PubMed  Google Scholar 

  • CHAO, M. V. & BOTHWELL, M. (2002) Neurotrophins: To cleave or not to cleave. Neuron 33,–12.

    PubMed  Google Scholar 

  • CHITNIS, A. B. (1999) Control of neurogenesis—Lessons from frogs, fish and flies. Curr. Opin. Neurobiol. 9, 1–25.

    PubMed  Google Scholar 

  • FU, A. K., IP, F. C., LAI, K. O., TSIM, K. W. & IP, N. Y. (1997) Muscle-derived neurotrophin-3 increases the aggregation of acetylcholine receptors in neuron-muscle cocultures. Neuroreport 8, 389–3900.

    PubMed  Google Scholar 

  • FUNAKOSHI, H., BELLUARDO, N., ARENAS, E., YAMAMOTO, Y., CASABONA, A., PERSSON, H. & IBANEZ, C. F. (1995) Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons. Science 268, 149–1499.

    PubMed  Google Scholar 

  • GAGE, F. H., BATCHELOR, P., CHEN, K. S., CHIN, D., HIGGINS, G. A., KOH, S., DEPUTY, S., ROSENBERG, M. B., FISCHER, W. & BJORKLUND, A. (1989) NGF receptor reexpression and NGF-mediated cholinergic neuronal hypertrophy in the damaged adult neostriatum. Neuron 2, 117–1184.

    PubMed  Google Scholar 

  • GARCES, A., HAASE, G., AIRAKSINEN, M. S., LIVET, J., FILIPPI, P. & DELAPEYRIERE, O. (2000) GFRalpha 1 is required for development of distinct subpopulations of motoneuron. J. Neurosci. 20, 499–5000.

    PubMed  Google Scholar 

  • GOLDEN, J. P., DEMARO, J. A., OSBORNE, P. A., MILBRANDT, J. & JOHNSON, E. M., JR. (1999) Expression of neurturin,GDNF, andGDNFfamily-receptor mRNAin the developing and mature mouse. Exp. Neurol. 158, 50–528.

    PubMed  Google Scholar 

  • GOMEZ-PINILLA, F., YING, Z., OPAZO, P., ROY, R. R. & EDGERTON, V. R. (2001) Differential regulation by exercise of BDNF and NT-3 in rat spinal cord and skeletal muscle. Eur. J. Neurosci. 13, 107–1084.

    PubMed  Google Scholar 

  • GOMEZ-PINILLA, F., YING, Z., ROY, R. R., MOLTENI, R. & EDGERTON, V. R. (2002) Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J. Neurophysiol. 88, 218–2195.

    PubMed  Google Scholar 

  • GONZALEZ, M., RUGGIERO, F. P., CHANG, Q., SHI, Y. J., RICH, M. M., KRANER, S. & BALICEGORDON, R. J. (1999) Disruption of Trkb-mediated signaling induces disassembly of postsynaptic receptor clusters at neuromuscular junctions. Neuron 24, 56–583.

    PubMed  Google Scholar 

  • HALL, A. C., LUCAS, F. R. & SALINAS, P. C. (2000) Axonal remodeling and synaptic differentiation in the cerebellum is regulated by WNT-7a signaling. Cell 100, 52–535.

    PubMed  Google Scholar 

  • HE, X., YANG, F., XIE, Z. & LU, B. (2000) Intracellular Ca2+ and Ca2+/Calmodulin-dependent kinase II mediate acute potentiation of neurotransmitter release by neurotrophin-3. J. Cell Biol. 149, 78–792.

    PubMed  Google Scholar 

  • HENDERSON, C. E., CAMU, W., METTLING, C., GOUIN, A., POULSEN, K., KARIHALOO, M., RULLAMAS, J., EVANS, T., MCMAHON, S. B., ARMANINI, M. P., BERKEMEIER, L., PHILLIPS, H. S. & ROSENTHAL, A. (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363, 26–270.

    Google Scholar 

  • HENDERSON, C. E., PHILLIPS, H. S., POLLOCK, R. A., DAVIES, A. M., LEMEULLE, C., ARMANINI, M., SIMMONS, L., MOFFET, B., VANDLEN, R. A., SIMPSON, L. C., KOLIATSOS, V. E. & ROSENTHAL, A. (1994) GDNF: A potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266, 106–1064.

    PubMed  Google Scholar 

  • HO, T. W., BRISTOL, L. A., COCCIA, C., LI, Y., MILBRANDT, J., JOHNSON, E., JIN, L., BAR-PELED, O., GRIFFIN, J. W. & ROTHSTEIN, J. D. (2000) TGFbeta trophic factors differentially modulate motor axon outgrowth and protection from excitotoxicity. Exp. Neurol. 161, 66–675.

    PubMed  Google Scholar 

  • HUANG, E. J. & REICHARDT, L. F. (2001) Neurotrophins: Roles in neuronal development and function. Ann. Rev. Neurosci. 24, 67–736.

    PubMed  Google Scholar 

  • HUELSKEN, J. & BIRCHMEIER, W. (2001) New aspects of Wnt signaling pathways in higher vertebrates. Current Opinion in Genetics & Development 11, 54–553.

    Google Scholar 

  • KAPLAN, D. R. & MILLER, F. D. (2000) Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 10, 38–391.

    PubMed  Google Scholar 

  • KELLER-PECK, C. R., FENG, G., SANES, J. R., YAN, Q., LICHTMAN, J. W. & SNIDER, W. D. (2001) Glial cell line-derived neurotrophic factor administration in postnatal life results in motor unit enlargement and continuous synaptic remodeling at the neuromuscular junction. J. Neurosci. 21, 613–6146.

    PubMed  Google Scholar 

  • KLEIMAN, R. J., TIAN, N., KRIZAJ, D., HWANG, T. N., COPENHAGEN, D. R. & REICHARDT, L. F. (2000) BDNF-Induced potentiation of spontaneous twitching in innervated myocytes requires calcium release fromintracellular stores. J. Neurophysiol. 84, 47–483.

    PubMed  Google Scholar 

  • KOLIATSOS, V. E., CLATTERBUCK, R. E., WINSLOW, J. W., CAYOUETTE, M. H. & PRICE, D. L. (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10, 35–367.

    PubMed  Google Scholar 

  • KRIEGLSTEIN, K., HENHEIK, P., FARKAS, L., JASZAI, J., GALTER, D., KROHN, K. & UNSICKER, K. (1998) Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons. J. Neurosci. 18, 982–9834.

    PubMed  Google Scholar 

  • KRYLOVA, O., HERREROS, J., CLEVERLEY, K. E., EHLER, E., HENRIQUEZ, J. P., HUGHES, S. M. & SALINAS, P. C. (2002) WNT-3, expressed by motoneurons, regulates terminal arborization of neurotrophin-3-responsive spinal sensory neurons. Neuron 35, 104–1056.

    PubMed  Google Scholar 

  • LEE, R., KERMANI, P., TENG, K. K. & HEMPSTEAD, B. L. (2002) Regulation of cell survival by secreted proneurotrophins. Science 294, 194–1948.

    Google Scholar 

  • LEITNER, M. L., MOLLIVER, D. C., OSBORNE, P. A., VEJSADA, R., GOLDEN, J. P., LAMPE, P. A., KATO, A. C., MILBRANDT, J. & JOHNSON, E. M., JR. (1999) Analysis of the retrograde transport of glial cell line-derived neurotrophic factor (GDNF), neurturin, and persephin suggests that in vivo signaling for the GDNF family is GFRalpha coreceptor-specific. J. Neurosci. 19, 932–9331.

    PubMed  Google Scholar 

  • LEWIN, G. R. & BARDE, Y.-A. (1996) Physiology of the neurotrophins. Annu. Rev. Neurosci. 19, 28–317.

    PubMed  Google Scholar 

  • LI, H. S., XU, X. Z. & MONTELL, C. (1999) Activation of a TRPC3-dependent cation current through the neurotrophin BDNF. Neuron 24, 26–273.

    PubMed  Google Scholar 

  • LIN, L. F., DOHERTY, D. H., LILE, J. D., BEKTESH, S. & COLLINS, F. (1993) GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260, 113–1132.

    PubMed  Google Scholar 

  • LINDEN, D. J. (1996) A protein synthesis-dependent late phase of cerebellar long-term depression. Neuron 17, 48–490.

    PubMed  Google Scholar 

  • LIOU, J. C. & FU, W. M. (1997) Regulation of quantal secretion from developing motoneurons by postsynaptic activity-dependent release of NT-3. J. Neurosci. 17, 245–2468.

    PubMed  Google Scholar 

  • LIOU, J. C., YANG, R. S. & FU, W. M. (1997) Regulation of quantal secretion by neurotrophic factors at developing motoneurons in Xenopus cell cultures. J. Physiol. (Lond.) 503, 12–139.

    Google Scholar 

  • LOEB, J. A. & FISCHBACH, G. D. (1997) Neurotrophic factors increase neuregulin expression in embryonic ventral spinal cord neurons. J. Neurosci. 17, 141–1424.

    PubMed  Google Scholar 

  • LOEB, J. A., HMADCHA, A., FISCHBACH, G. D., LAND, S. J. & ZAKARIAN, V. L. (2002) Neuregulin expression at neuromuscular synapses is modulated by synaptic activity and neurotrophic factors. J. Neurosci. 22, 220–2214.

    PubMed  Google Scholar 

  • LOHOF, A. M., IP, N. Y. & POO, M. M. (1993) Potentiation of developing neuromuscular synapses by the neurotrophins NT-3 and BDNF. Nature 363, 35–353.

    PubMed  Google Scholar 

  • LU, B. & FIGUROV, A. (1997) Role of neurotrophins in synapse development and plasticity. Rev. Neurosci. 8, –12.

    PubMed  Google Scholar 

  • MARQUES, G., BAO, H., HAERRY, T. E., SHIMELL, M. J., DUCHEK, P., ZHANG, B. & O'CONNOR, M. B. (2002) The Drosophila BMP type II receptor Wishful Thinking regulates neuromuscular synapse morphology and function. Neuron 33, 52–543.

    PubMed  Google Scholar 

  • MASSAGUE, J. (1998) TGF-beta signal transduction. Annu. Rev. Biochem. 67, 75–791.

    PubMed  Google Scholar 

  • MASSAGUE, J. (2000) How cells read TGF-beta signals. Nat. Rev. Mol. Cell Biol. 1, 16–178.

    PubMed  Google Scholar 

  • MCLENNAN, I. S. & KOISHI, K. (1994) Transforming growth factor-beta-2 (TGF-beta 2) is associated with mature rat neuromuscular junctions. Neuroscience Letters 177, 15–154.

    PubMed  Google Scholar 

  • MIKAELS, A., LIVET, J., WESTPHAL, H., DE LAPEYRIERE, O. & ERNFORS, P. (2000) A dynamic regulation of GDNF-family receptors correlates with a specific trophic dependency of cranial motor neuron subpopulations during development. Eur. J. Neurosci. 12, 44–456.

    PubMed  Google Scholar 

  • MILBRANDT, J., DE SAUVAGE, F. J., FAHRNER, T. J., BALOH, R. H., LEITNER, M. L., TANSEY, M. G., LAMPE, P. A., HEUCKEROTH, R. O., KOTZBAUER, P. T., SIMBURGER, K. S., GOLDEN, J. P., DAVIES, J. A., VEJSADA, R., KATO, A. C., HYNES, M., SHERMAN, D., NISHIMURA, M., WANG, L. C., VANDLEN, R., MOFFAT, B., KLEIN, R. D., POULSEN, K., GRAY, C., GARCES, A., JOHNSON, E. M., JR. et al. (1998) Persephin, a novel neurotrophic factor related to GDNF and neurturin. Neuron 20, 24–253.

    PubMed  Google Scholar 

  • MING, G. L., WONG, S. T., HENLEY, J., YUAN, X. B., SONG, H. J., SPITZER, N. C. & POO, M. M. (2002) Adaptation in the chemotactic guidance of nerve growth cones. Nature 417, 41–418.

    PubMed  Google Scholar 

  • MOORE, M. W., KLEIN, R. D., FARINAS, I., SAUER, H., ARMANINI, M., PHILLIPS, H., REICHARDT, L. F., RYAN, A. M., CARVER, M. K. & ROSENTHAL, A. (1996) Renal and neuronal abnormalities in mice lacking GDNF. Nature 382, 7–79.

    PubMed  Google Scholar 

  • NGUYEN, Q. T., PARSADANIAN, A. S., SNIDER, W. D. & LICHTMAN, J. W. (1998) Hyperinnervation of neuromuscular junctions caused by GDNF overexpression in muscle. Science 279, 172–1729.

    PubMed  Google Scholar 

  • NICK, T. A. & RIBERA, A. B. (2000) Synaptic activity modulates presynaptic excitability. Nat. Neurosci. 3, 14– 149.

    PubMed  Google Scholar 

  • OLAFSSON, P., SOARES, H. D., WANG, T., HERZOG, K.-H., MORGAN, J. I. & LU, B. (1997) The Ca2+ binding protein frequenin is a nervous system-specific protein preferentially localized in neurites. Mol. Brain Res. 44, 7–82.

    PubMed  Google Scholar 

  • OPPENHEIM, R. W., YIN, Q.-W., PREVETTE, D. & YAN, Q. (1992) Brain-derived neurotrophic factor rescues developing avian motorneurons fromcell death. Nature 360, 75–757.

    PubMed  Google Scholar 

  • OPPENHEIM, R. W., HOUENOU, L. J., JOHNSON, J. E., LIN, L. F., LI, L., LO, A. C., NEWSOME, A. L., PREVETTE, D. M. & WANG, S. (1995) Developing motor neurons rescued from programmed and axotomyinduced cell death by GDNF. Nature 373, 34–346.

    PubMed  Google Scholar 

  • OPPENHEIM, R. W., HOUENOU, L. J., PARSADANIAN, A. S., PREVETTE, D., SNIDER, W. D. & SHEN, L. (2000) Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: Regulation of programmed cell death among motoneuron subtypes. J. Neurosci. 20, 500–5011.

    PubMed  Google Scholar 

  • PACKARD, M., KOO, E. S., GORCZYCA, M., SHARPE, J., CUMBERLEDGE, S. & BUDNIK, V. (2002) The Drosophila Wnt, wingless, provides an essential signal for pre-and postsynaptic differentiation. Cell 111, 31–330.

    PubMed  Google Scholar 

  • SANCHEZ, M. P., SILOS, S. I., FRISEN, J., HE, B., LIRA, S. A. & BARBACID, M. (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382, 7–73.

    PubMed  Google Scholar 

  • SANES, J. R. & LICHTMAN, J. W. (1999) Development of the vertebrate neuromuscular junction. Annu. Rev. Neurosci. 22, 38–442.

    PubMed  Google Scholar 

  • SENDTNER, M., HOLTMANN, B., KOLBECK, R., THOENEN, H. & BARDE, Y.-A. (1992) Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section. Nature 360, 75–759.

    PubMed  Google Scholar 

  • SONG, H., MING, G., HE, Z., LEHMANN, M., TESSIERLAVIGNE, M. & POO, M. (1998) Conversion of neuronal growth cone responses from repulsion to attraction by cyclic nucleotides. Science 281, 151–1518.

    PubMed  Google Scholar 

  • SONG, H. J. & POO, M. M. (1999) Signal transduction underlying growth cone guidance by diffusible factors. Curr. Opin. Neurobiol. 9, 35–363.

    PubMed  Google Scholar 

  • STOOP, R. & POO, M. M. (1995) Potentiation of transmitter release by ciliary neurotrophic factor requires somatic signaling. Science 267, 69–699.

    PubMed  Google Scholar 

  • STOOP, R. & POO, M. M. (1996) Synaptic modulation by neurotrophic factors: Differential and synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor. J. Neurosci. 16, 325–3264.

    PubMed  Google Scholar 

  • SWEENEY, S. T. & DAVIS, G. W. (2002) Unrestricted synaptic growth in spinster—A late endosomal protein implicated in TGF-[Beta;]-mediated synaptic growth regulation. Neuron 36, 40–416.

    PubMed  Google Scholar 

  • TAKEI, N., KAWAMURA, M., HARA, K., YONEZAWA, K. & NAWA, H. (2001) Brain-derived neurotrophic factor enhances neuronal translation by activating multiple initiation processes: Comparison with the effects of insulin. J. Biol. Chem. 276, 4281–42825.

    PubMed  Google Scholar 

  • TREANOR, J. J., GOODMAN, L., DE, S. F., STONE, D. M., POULSEN, K. T., BECK, C. D., GRAY, C., ARMANINI, M. P., POLLOCK, R. A., HEFTI, F., PHILLIPS, H. S., GODDARD, A., MOORE, M. W., BUJ, B. A., DAVIES, A. M., ASAI, N., TAKAHASHI, M., VANDLEN, R., HENDERSON, C. E. & ROSENTHAL, A. (1996) Characterization of a multicomponent receptor for GDNF. Nature 382, 8–83.

    PubMed  Google Scholar 

  • WANG, C., YANG, F., HE, X., CHOW, A., DU, J., RUSSELL, J. & LU, B. (2001) Ca2+-binding protein frequenin mediates GDNF-induced synaptic facilitation by potentiating Ca2+ channels. Neuron 32, 9–112.

    Google Scholar 

  • WANG, C. Y., YANG, F., HE, X. P., JE, H. S., ZHOU, J. Z., ECKERMANN, K., KAWAMURA, D., FENG, L., SHEN, L. & LU, B. (2002) Regulation of neuromuscular synapse development by glial cell line-derived neurotrophic factor and neurturin. J. Biol. Chem. 277, 1061–10625.

    PubMed  Google Scholar 

  • WANG, T., XIE, K. W. & LU, B. (1995) Neurotrophins promote maturation of developing neuromuscular synapses. J. Neurosci. 15, 479–4805.

    PubMed  Google Scholar 

  • WANG, X. H. & POO, M. M. (1997) Potentiation of developing synapses by postsynaptic release of neurotrophin-4. Neuron 19, 82–835.

    PubMed  Google Scholar 

  • WELLS, D. G., MCKECHNIE, B. A., KELKAR, S. & FALLON, J. R. (1999) Neurotrophins regulate agrininduced postsynaptic differentiation. Proc. Natl. Acad. Sci. USA 96, 111–1117.

    PubMed  Google Scholar 

  • WIDENFALK, J., NOSRAT, C., TOMAC, A., WESTPHAL, H., HOFFER, B. & OLSON, L. (1997) Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs. J. Neurosci. 17, 850–8519.

    PubMed  Google Scholar 

  • WONG, V., ARRIAGA, R., IP, N. Y. & LINDSAY, R. M. (1993) The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, upregulate the cholinergic phenotype of developing motor neurons. Eur. J. Neurosci. 5, 46–474.

    PubMed  Google Scholar 

  • XIE, K., WANG, T., OLAFSSON, P., MIZUNO, K. & LU, B. (1997) Activity-dependent expression of NT-3 in muscle cells in culture: Implication in the development of neuromuscular junctions. J. Neurosci. 17, 294–2958.

    PubMed  Google Scholar 

  • YAN, Q., ELLIOTT, J. & SNIDER, W. D. (1992) Brainderived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Nature 360, 75–755.

    PubMed  Google Scholar 

  • YAN, Q., ELLIOTT, J. L., MATHESON, C., SUN, J., ZHANG, L., MU, X., REX, K. L. & SNIDER, W. D. (1993) Influences of neurotrophins on mammalian motoneurons in vivo. J. Neurobiol. 24, 155–1577.

    PubMed  Google Scholar 

  • YAN, Q., MATHESON, C. & LOPEZ, O. T. (1995) In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons. Nature 373, 34–344.

    PubMed  Google Scholar 

  • YANG, F., HE, X., FENG, L., MIZUNO, K., LIU, X., RUSSELL, J., XIONG, W. & LU, B. (2001) PI3 kinase and IP3 are both necessary and sufficient to mediate NT3-induced synaptic potentiation. Nature Neurosci. 4, 1–28.

    PubMed  Google Scholar 

  • ZHANG, X. & POO, M. M. (2002) Localized synaptic potentiation by BDNF requires local protein synthesis in the developing axon. Neuron 36, 67–688.

    PubMed  Google Scholar 

  • ZWICK, M., TENG, L., MU, X., SPRINGER, J. E. & DAVIS, B. M. (2001) Overexpression of GDNF induces and maintains hyperinnervation of muscle fibers and multiple end-plate formation. Exp. Neurol. 171, 34– 350.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Section on Neural Development & Plasticity, NICHD, NIH, Bethesda, MD, 20892-4480, USA

    Bai Lu & Hyun-Soo Je

Authors
  1. Bai Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyun-Soo Je
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, B., Je, HS. Neurotrophic regulation of the development and function of the neuromuscular synapses. J Neurocytol 32, 931–941 (2003). https://doi.org/10.1023/B:NEUR.0000020633.93430.db

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEUR.0000020633.93430.db

Keywords

Search

Navigation