Macromolecular connections of active zone material to docked synaptic vesicles and presynaptic membrane at neuromuscular junctions of mouse

Electron tomography was used to view macromolecules composing active zone material (AZM) in axon terminals at mouse neuromuscular junctions. Connections of the macromolecules to each other, to calcium channels in the presynaptic membrane, and to synaptic vesicles docked on the membrane prior to fusing with it during synaptic transmission were similar to those of AZM macromolecules at frog neuromuscular junctions previously examined by electron tomography and support the hypothesis that AZM regulates vesicle docking and fusion. A species difference in the arrangement of AZM relative to docked vesicles may help account for a greater vesicle‐presynaptic membrane contact area during docking and a greater probability of fusion during synaptic transmission in mouse. Certain AZM macromolecules in mouse were connected to synaptic vesicles contacting the presynaptic membrane at sites where fusion does not occur. These secondary docked vesicles had a different relationship to the membrane and AZM macromolecules than primary docked vesicles, consistent with their having a different AZM‐regulated behavior. J. Comp. Neurol. 513:457–468, 2009. © 2009 Wiley‐Liss, Inc.

[1]  E. Wright,et al.  Conical Electron Tomography of a Chemical Synapse: Polyhedral Cages Dock Vesicles to the Active Zone , 2008, The Journal of Neuroscience.

[2]  Maryann E Martone,et al.  The combination of chemical fixation procedures with high pressure freezing and freeze substitution preserves highly labile tissue ultrastructure for electron tomography applications. , 2008, Journal of structural biology.

[3]  Paul Greengard,et al.  Three-Dimensional Architecture of Presynaptic Terminal Cytomatrix , 2007, The Journal of Neuroscience.

[4]  Helmut Grubmüller,et al.  Molecular Anatomy of a Trafficking Organelle , 2006, Cell.

[5]  L M Zampighi,et al.  Conical electron tomography of a chemical synapse: vesicles docked to the active zone are hemi-fused. , 2006, Biophysical journal.

[6]  I. Meinertzhagen,et al.  Development and structure of synaptic contacts in Drosophila. , 2006, Seminars in cell & developmental biology.

[7]  R. C. Morrison,et al.  Appendix a a " Flip-flop " Rotation Stage for Routine Dual-axis Electron Cryotomography , 2005 .

[8]  W. Betz,et al.  Synaptic vesicle pools , 2005, Nature Reviews Neuroscience.

[9]  David B Ress,et al.  Methods for generating high-resolution structural models from electron microscope tomography data. , 2004, Structure.

[10]  H. Bellen,et al.  The architecture of the active zone in the presynaptic nerve terminal. , 2004, Physiology.

[11]  D. Agard,et al.  An improved strategy for automated electron microscopic tomography. , 2004, Journal of structural biology.

[12]  T. Sudhof,et al.  The synaptic vesicle cycle. , 2004, Annual review of neuroscience.

[13]  David Ress,et al.  Optimization method for isodensity surface models obtained with electron microscope tomography data , 2003, Proceedings of the 25th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (IEEE Cat. No.03CH37439).

[14]  Arne Stoschek,et al.  The architecture of active zone material at the frog's neuromuscular junction , 2001, Nature.

[15]  C. Garner,et al.  The presynaptic cytomatrix of brain synapses , 2001, Cellular and Molecular Life Sciences CMLS.

[16]  R. S. Wilkinson,et al.  Endocytic Active Zones: Hot Spots for Endocytosis in Vertebrate Neuromuscular Terminals , 1999, The Journal of Neuroscience.

[17]  D Ress,et al.  Automatic acquisition of fiducial markers and alignment of images in tilt series for electron tomography. , 1999, Journal of electron microscopy.

[18]  P. Pawson,et al.  Quantitative freeze-fracture analysis of the frog neuromuscular junction synapse – I. Naturally occurring variability in active zone structure , 1998, Journal of neurocytology.

[19]  J. Frank,et al.  Double-tilt electron tomography. , 1995, Ultramicroscopy.

[20]  J. Walrond,et al.  Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  Richard Robitaille,et al.  Functional colocalization of calcium and calcium-gated potassium channels in control of transmitter release , 1993, Neuron.

[22]  A J Hudspeth,et al.  Colocalization of ion channels involved in frequency selectivity and synaptic transmission at presynaptic active zones of hair cells , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[23]  N. Hirokawa,et al.  The cytoskeletal architecture of the presynaptic terminal and molecular structure of synapsin 1 , 1989, The Journal of cell biology.

[24]  A. Engel,et al.  Lambert‐eaton myasthenic syndrome IgG depletes presynaptic membrane active zone particles by antigenic modulation , 1988, Annals of neurology.

[25]  J. Walrond,et al.  Structural and functional correlates of synaptic transmission in the vertebrate neuromuscular junction. , 1988, Journal of electron microscopy technique.

[26]  T. Reese,et al.  The organization of cytoplasm at the presynaptic active zone of a central nervous system synapse , 1988, Neuron.

[27]  J. Molgó,et al.  The levator auris longus muscle of the mouse: A convenient preparation for studies of short- and long-term presynaptic effects of drugs or toxins , 1987, Neuroscience Letters.

[28]  C. Peers,et al.  The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. , 1987, The Journal of physiology.

[29]  A. Engel,et al.  Lambert‐Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones , 1987, Annals of neurology.

[30]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[31]  J. Walrond,et al.  Structure of axon terminals and active zones at synapses on lizard twitch and tonic muscle fibers , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[32]  J. Heuser,et al.  Endocytosis of synaptic vesicle membrane at the frog neuromuscular junction , 1984, The Journal of cell biology.

[33]  A. Engel,et al.  Passive transfer of Lambert-Eaton myasthenic syndrome with IgG from man to mouse depletes the presynaptic membrane active zones. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Banker,et al.  Neuromuscular transmission and correlative morphology in young and old mice , 1983, The Journal of physiology.

[35]  M. Fahim,et al.  Scanning and light microscopic study of age changes at a neuromuscular junction in the mouse , 1983, Journal of neurocytology.

[36]  A. Engel,et al.  Paucity and disorganization of presynaptic membrane active zones in the lambert‐eaton myasthenic syndrome , 1982 .

[37]  T. Reese,et al.  Structural changes after transmitter release at the frog neuromuscular junction , 1981, The Journal of cell biology.

[38]  Mark Ellisman,et al.  Studies of excitable membranes. II. A comparison of specializations at neuromuscular junctions and nonjunctional sarcolemmas of mammalian fast and slow twitch muscle fibers , 1976, The Journal of cell biology.

[39]  Mark Ellisman,et al.  STUDIES OF EXCITABLE MEMBRANES: I. Macromolecular Specializations of the Neuromuscular Junction and the Nonjunctional Sarcolemma , 1974 .

[40]  T. Reese,et al.  Functional changes in frog neuromuscular junctions studied with freeze-fracture , 1974, Journal of neurocytology.

[41]  T. Reese,et al.  EVIDENCE FOR RECYCLING OF SYNAPTIC VESICLE MEMBRANE DURING TRANSMITTER RELEASE AT THE FROG NEUROMUSCULAR JUNCTION , 1973, The Journal of cell biology.

[42]  M. Carpenter.  The Fine Structure of the Nervous System , 1970, Neurology.

[43]  V. Tennyson.  The Fine Structure of the Nervous System. , 1970 .

[44]  J. Simpson.  THE RELEASE OF NEURAL TRANSMITTER SUBSTANCES , 1969 .

[45]  E. Gray.  Problems of Interpreting the Fine Structure of Vertebrate and Invertebrate Synapses , 1966 .

[46]  Karl Pearson F.R.S..  LIII. On lines and planes of closest fit to systems of points in space , 1901 .