Skip to main content
Log in

Axonal terminals of sensory neurons and their morphological diversity

  • Published:
Journal of Neurocytology

Abstract

The application of electron microscopy to defining the fine structural characteristics of axon terminals and synapses was followed by a half century of intensive exploration of the molecular concomitants of synaptic activity. The summer of 2003 marks the 50th anniversary of the earliest accounts of synapses by Palay and Palade.

Prompted by recent findings of specialization in the fine structure of nociceptor terminals that lack contacts remotely resembling a synapse, we present a survey of arrangements, contacts and axoplasmic contents of peripheral sensory axon terminals. The morphological principles underlying the variety of small, clear, spherical vesicles, mitochondrial aggregation, the membrane thickenings associated with sensory terminals and the organelles or inclusions associated with the site of transduction apparently do not conform to a simple parsimonious rule. It is also evident that the terminal of the central branch of bifurcated sensory axons differs structurally from its distal counterparts. This brief illustrated account addresses some important unresolved problems in the functional interpretation of the diverse morphological features exhibited in both synaptic and non-synaptic sensory axon terminals with the aim of identifying and emphasizing some key questions amenable to resolution with contemporary morphological and physiological techniques.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • AKERT, K., PFENNINGER, K., SANDRI, C. & MOOR, H. (1972) Freeze etching and cytochemistry of vesicles and membrane complexes in synapses of the central nervous system. In Structure and Function of Synapses (edited by Pappas, G. D. & Purpura, D. P.) pp. 67–86. New York: Raven Press.

    Google Scholar 

  • ALVAREZ, F. J., KAVOOKJIAN, A. M. & LIGHT, A. R. (1993) Ultrastructural morphology, synaptic relationships, and CGRP immunoreactivity of physiologically identified C-fiber terminals in the monkey spinal cord. Journal of Comparative Neurology 329, 472–490.

    PubMed  Google Scholar 

  • ANDRES, K. H. (1969) On the ultrastructure of various mechanoreceptors of higher vertebrates. Anatomischer Anzeiger 124, 551–565.

    PubMed  Google Scholar 

  • ANDRES, K. H. & VON DÑRING, M. (1973) Morphology of cutaneous receptors. In Handbook of Sensory Physiology (edited by Iggo, A.) pp. 3–28. Berlin,NewYork: Springer-Verlag.

    Google Scholar 

  • BELL, J., BOLANOWSKI, S. & HOLMES, M. H. (1994) The structure and function of Pacinian corpuscles: A review. Progress in Neurobiology 42, 79–128.

    PubMed  Google Scholar 

  • BOLANOWSKI, S. J., SCHYULER, J. E. & SLEPECKY, N. B. (1994) Semi-serial electron-micrographic reconstruction of putative transducer sites in Pacinian corpuscles. Somatosensory and Motor Research 11, 205–218.

    PubMed  Google Scholar 

  • BRITTIS, P. A., LU, Q. & FLANAGAN, J. G. (2002) Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. Cell 110, 223–235.

    PubMed  Google Scholar 

  • BURGESS, P. R. & PERL, E. R. (1967) Myelinated afferent fibres responding specifically to noxious stimulation of the skin. Journal of Physiology 190, 541–562.

    PubMed  Google Scholar 

  • CARLTON, S. M., HARGETT, G. L. & COGGESHALL, R. E. (1995) Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. Neuroscience Letters 197, 25–28.

    PubMed  Google Scholar 

  • CARLTON, S. M., ZHOU, S. & COGGESHALL, R. E. (1998) Evidence for the interaction of glutamate and NK1 receptors in the periphery. Brain Research 790, 160–169.

    PubMed  Google Scholar 

  • CATERINA, M. J. & JULIUS, D. (2001) The vanilloid receptor: A molecular gateway to the pain pathway. Annual Review of Neuroscience 24, 487–517.

    PubMed  Google Scholar 

  • CHEN, C. C., AKOPIAN, A. N., SIVILOTTI, L., COLQUHOUN, D., BURNSTOCK, G. & WOOD, J. N. (1995) A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377, 428–431.

    PubMed  Google Scholar 

  • CHUANG, H. H., PRESCOTT, E. D., KONG, H., SHIELDS, S., JORDT, S. E., BASBAUM, A. I., CHAO, M. V. & JULIUS, D. (2001) Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411, 957–962.

    PubMed  Google Scholar 

  • DELAY, R. J. & ROPER, S. D. (1988) Ultrastructure of taste cells and synapses in the mudpuppy Necturus maculosus. Journal of Comparative Neurology 277, 268–280.

    PubMed  Google Scholar 

  • DEMEMES, D., SEOANE, A., VENTEO, S. & DESMADRYL, G. (2000) Efferent function of vestibular afferent endings? Similar localization of N-type calcium channels, synaptic vesicle and synaptic membraneassociated proteins. Neuroscience 98, 377–384.

    PubMed  Google Scholar 

  • DIAMOND, J., MILLS, L. R. & MEAROW, K. M. (1988) Evidence that the Merkel cell is not the transducer in the mechanosensory Merkel cell-neurite complex. Progress in Brain Research 74, 51–56.

    PubMed  Google Scholar 

  • DROZ, B., RAMBOURG, A. & KOENIG, H. L. (1975) The smooth endoplasmic reticulum: Structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport. Brain Research 93, 1–13.

    PubMed  Google Scholar 

  • DUGGAN, A., GARCIA-ANOVEROS, J. & COREY, D. P. (2002) The PDZ domain protein PICK1 and the sodium channel BNaC1 interact and localize at mechanosensory terminals of dorsal root ganglion neurons and dendrites of central neurons. Journal of Biological Chemistry 277, 5203–5208.

    PubMed  Google Scholar 

  • EDMONDS, B., GREGORY, F. D. & SCHWEIZER, F. E. (submitted) Undocked vesicles contribute to fast exocytosis in frog saccular hair cells.

  • GARCIA-ANOVEROS, J., SAMAD, T. A., ZUVELAJELASKA, L., WOOLF, C. J. & COREY, D. P. (2001) Transport and localization of theDEG/ENaCion channel BNaC1alpha to peripheral mechanosensory terminals of dorsal root ganglia neurons. Journal of Neuroscience 21, 2678–2686.

    PubMed  Google Scholar 

  • GIUDITTA, A., KAPLAN, B. B., VAN MINNEN, J., ALVAREZ, J. & KOENIG, E. (2002) Axonal and presynaptic protein synthesis: New insights into the biology of the neuron. Trends in Neurosciences 25, 400–404.

    PubMed  Google Scholar 

  • GRAY, J. A. B. & MATTHEWS, P. B. C. (1951) A comparison of the adaptation of the Pacinian corpuscle with the adaptation of its own axon. Journal of Physiology 114, 454–464.

    PubMed  Google Scholar 

  • GRAY, J. A. B. & SATO, M. (1953) Properties of the receptor potential in Pacinian corpuscles. Journal of Physiology 122, 610–636.

    PubMed  Google Scholar 

  • GUNTHORPE, M. J., BENHAM, C. D., RANDALL, A. & DAVIS, J. B. (2002) The diversity in the vanilloid (TRPV) receptor family of ion channels. Trends in Pharmacological Sciences 23, 183–191.

    PubMed  Google Scholar 

  • GUO, A., VULCHANOVA, L., WANG, J., LI, X. & ELDE, R. (1999) Immunocytochemical localization of the vanilloid receptor 1 (VR1): Relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. European Journal of Neuroscience 11, 946–958.

    PubMed  Google Scholar 

  • HEPPLEMANN, B., MESSLINGER, K., NEISS, W. F. & SCHMIDT, R. F. (1990) The sensory terminal tree of “free nerve endings” in the articular capsule of the knee. In The Primary Afferent Neuron:ASurvey of Recent Morpho-Functional Aspects (edited by Zenker, W. & Neuhuber, W. L.), pp. 73–85. New York: Plenum Press.

    Google Scholar 

  • IMMKE, D. C. & MCCLESKEY, E. W. (2001) Lactate enhances the acid-sensing Na+ channel on ischemiasensing neurons. Nature Neuroscience 4, 869–870.

    PubMed  Google Scholar 

  • IMMKE, D. C. & MCCLESKEY, E. W. (2003) Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade. Neuron 37, 75–84.

    PubMed  Google Scholar 

  • JUNG, J., HWANG, S. W., KWAK, J., LEE, S. Y., KANG, C. J., KIM, W. B., KIM, D. & OH, U. (1999) Capsaicin binds to the intracellular domain of the capsaicinactivated ion channel. Journal of Neuroscience 19, 529–538.

    PubMed  Google Scholar 

  • KELLENBERGER, S. & SCHILD, L. (2002) Epithelial sodium channel/degenerin family of ion channels:Avariety of functions for a shared structure. Physiological Reviews 82, 735–767.

    PubMed  Google Scholar 

  • KINNAMON, J. C., SHERMAN, T. A. & ROPER, S. D. (1988) Ultrastructure of mouse vallate taste buds: III. Patterns of synaptic connectivity. Journal of Comparative Neurology 270, 1–10, 56–57.

    PubMed  Google Scholar 

  • KINNAMON, J. C., TAYLOR, B. J., DELAY, R. J. & ROPER, S. D. (1985) Ultrastructure of mouse vallate taste buds. I. Taste cells and their associated synapses. Journal of Comparative Neurology 235, 48–60.

    PubMed  Google Scholar 

  • KRUGER, L., KAVOOKJIAN, A. M., KUMAZAWA, T., LIGHT, A. R. & MIZUMURA, K. (2003) Nociceptor structural specialization in canine and rodent testicular “free” nerve endings. Journal of Comparative Neurology 463, 197–211.

    PubMed  Google Scholar 

  • KRUGER, L. & MANTYH, P. W. (1989) Gustatory and related chemosensory systems. In Handbook of Chemical Neuroanatomy, vol.7: Integrated Systems of the CNS, Part II (edited by Björklund, A., Hökfelt, T. & Swanson, L. W.) pp. 323–411. Amsterdam: Elsevier.

    Google Scholar 

  • KRUGER, L., PERL, E. R. & SEDIVEC, M. J. (1981) Fine structure of myelinated mechanical nociceptor endings in cat hairy skin. Journal of Comparative Neurology 198, 137–154.

    PubMed  Google Scholar 

  • KUMAZAWA, T. (1996) The polymodal receptor: Biowarning and defense system. Progress in Brain Research 113, 3–18.

    PubMed  Google Scholar 

  • LEWIS, C., NEIDHART, S., HOLY, C., NORTH, R. A., BUELL, G. & SURPRENANT, A. (1995) Coexpression of P2X2 and P2X3 receptor subunits can account forATPgated currents in sensory neurons. Nature 377, 432–435.

    PubMed  Google Scholar 

  • LINDSEY, J. D. & ELLISMAN, M. H. (1985) The neuronal endomembrane system. I. Direct links between rough endoplasmic reticulum and the cis element of the Golgi apparatus. Journal of Neuroscience 5, 3111–3123.

    PubMed  Google Scholar 

  • LYSAKOWSKI, A. & GOLDBERG, J. M. (1997) A regional ultrastructural analysis of the cellular and synaptic architecture in the chinchilla cristae ampullares. Journal of Comparative Neurology 389, 419–443.

    PubMed  Google Scholar 

  • MARTINEZ-DUNST, C., MICHAELS, R. L. & FUCHS, P. A. (1997) Release sites and calcium channels in hair cells of the chick's cochlea. Journal of Neuroscience 17, 9133–9144.

    PubMed  Google Scholar 

  • McCLESKEY, E. W. & GOLD, M. S. (1999) Ion channels of nociception. Annual Review of Physiology 61, 835–856.

    PubMed  Google Scholar 

  • MESSLINGER, K. (1996) Functional morphology of nociceptive and other fine sensory endings (free nerve endings) in different tissues. Progress in Brain Research 113, 273–298.

    PubMed  Google Scholar 

  • MONTELL, C. (1997) New light on TRP and TRPL. Molecular Pharmacology 52, 755–763.

    PubMed  Google Scholar 

  • NORTH, R. A. (2002) Molecular physiology of P2X receptors. Physiological Reviews 82, 1013–1067.

    PubMed  Google Scholar 

  • OGAWA, H. (1996) The Merkel cell as a possible mechanoreceptor cell. Progress in Neurobiology 49, 317–334.

    PubMed  Google Scholar 

  • PALADE, G. E. & PALAY, S. L. (1954) Electron microscope observations of interneuronal and neuromuscular synapses. Anatomical Record 118, 335–336.

    Google Scholar 

  • PALAY, S. L. (1992) A concatenation of accidents. In The Neurosciences: Pathways of Discovery, II (edited by Samson, F. E. & Adelman, G.) pp. 191–212. Boston: Birkhäuser.

    Google Scholar 

  • PARSONS, T. D. & STERLING, P. (2003) Synaptic ribbon. Conveyor belt or safety belt? Neuron 37, 379–382.

    PubMed  Google Scholar 

  • PEASE, D. C. & QUILLIAM, T. A. (1957) Electron microscopy of the Pacinian corpuscle. Journal of Biophysical and Biochemical Cytology 3, 331–357.

    PubMed  Google Scholar 

  • PETERS, A., PALAY, S. L. & WEBSTER, H. D. (1991) The Fine Structure of the Nervous System. New York, Oxford: Oxford University Press.

    Google Scholar 

  • PFENNINGER, K., AKERT, K., MOOR, H. & SANDRI, C. (1972) The fine structure of freeze-fractured presynaptic membranes. Journal of Neurocytology 1, 129–149.

    PubMed  Google Scholar 

  • ROPER, S. D. (1992) The microphysiology of peripheral taste organs. Journal of Neuroscience 12, 1127–1134.

    PubMed  Google Scholar 

  • ROSS, M. D. (1997) Morphological evidence for local microcircuits in rat vestibular maculae. Journal of Comparative Neurology 379, 333–346.

    PubMed  Google Scholar 

  • SANKARANARAYANAN, S., ATLURI, P. P. & RYAN, T. A. (2003) Actin has a molecular scaffolding, not propulsive, role in presynaptic function. Nature Neuroscience 6, 127–135.

    PubMed  Google Scholar 

  • SCARFONE, E., DEMEMES, D., JAHN, R., DE CAMILLI, P. & SANS, A. (1988) Secretory function of the vestibular nerve calyx suggested by presence of vesicles, synapsin I, and synaptophysin. Journal of Neuroscience 8, 4640–4645.

    PubMed  Google Scholar 

  • SILVERMAN, J. D. & KRUGER, L. (1990) Selective neuronal glycoconjugate expression in sensory and autonomic ganglia: Relation of lectin reactivity to peptide and enzyme markers. Journal of Neurocytology 19, 789–801.

    PubMed  Google Scholar 

  • SOBKOWICZ, H. M., ROSE, J. E., SCOTT, G. L. & LEVENICK, C. V. (1986) Distribution of synaptic ribbons in the developing organ of Corti. Journal of Neurocytology 15, 693–714.

    PubMed  Google Scholar 

  • THIERS, F. A., BURGESS, B. J. & NADOL, J. B., JR. (2002) Reciprocal innervation of outer hair cells in a human infant. Journal of the Association for Research in Otolaryngology 3, 269–278.

    PubMed  Google Scholar 

  • VULCHANOVA, L., RIEDL, M. S., SHUSTER, S. J., STONE, L. S., HARGREAVES, K. M., BUELL, G., SURPRENANT, A., NORTH, R. A. & ELDE, R. (1998) P2X3 is expressed by DRG neurons that terminate in inner lamina II. European Journal of Neuroscience 10, 3470–3478.

    PubMed  Google Scholar 

  • YAMASHITA, M. & OHMORI, H. (1991) Synaptic bodies and vesicles in the calix type synapse of chicken semicircular canal ampullae. Neuroscience Letters 129, 43–46.

    PubMed  Google Scholar 

  • ZENISEK, D., DAVILA, V., WAN, L. & ALMERS, W. (2003) Imaging calcium entry sites and ribbon structures in two presynaptic cells. Journal of Neuroscience 23, 2538–2548.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kruger, L., Light, A.R. & Schweizer, F.E. Axonal terminals of sensory neurons and their morphological diversity. J Neurocytol 32, 205–216 (2003). https://doi.org/10.1023/B:NEUR.0000010080.62031.f0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NEUR.0000010080.62031.f0

Keywords

Navigation