Pflügers Archiv

, Volume 447, Issue 3, pp 363–370

Mitochondria and release at hippocampal synapses

Synaptic Transmission

Abstract

Mitochondria are present in some, but not all presynaptic terminals in the hippocampus. Mitochondria are capable of sequestering and storing large amounts of calcium, but it is unclear whether they influence release probability at these synapses. Using FM dye imaging techniques and confocal microscopy, we have examined the relationship between mitochondrial presence/absence and presynaptic vesicle release from rat hippocampal neurones in primary dissociated culture at room temperature. Following staining with the mitochondrial dye mitotracker green, we were able to resolve putative individual mitochondria associated with neuronal processes. The majority of mitochondria were positionally stable, although some exhibited periods of rapid motility (up to 0.4 μm/s) interspersed with periods of immobility. Co-staining with mitotracker green and the synaptic vesicle dye FM 4–64 indicated that 180 of 506 (36%) synapses were devoid of mitochondria. A comparison of vesicular release in response to stimulation at 1 Hz and at 10 Hz revealed no differences in release properties between synapses with and without mitochondria.

Keywords

Calcium FM 1–43 Mitochondrion Release probability Synapse 

References

  1. 1.
    Alnaes E, Rahamimoff R (1975) On the role of mitochondria in transmitter release from motor nerve terminals. J Physiol (Lond) 248:285–306Google Scholar
  2. 2.
    Betz WJ, Bewick GS (1992) Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255:200–203PubMedGoogle Scholar
  3. 3.
    Betz WJ, Mao F, Smith CB (1996) Imaging exocytosis and endocytosis. Curr Opin Neurobiol 6:365–371Google Scholar
  4. 4.
    Bouron A, Reuter H (1996) A role of intracellular Na+ in the regulation of synaptic transmission and turnover of the vesicular pool in cultured hippocampal cells. Neuron 17:969–978PubMedGoogle Scholar
  5. 5.
    Czurkó A, Hirase H, Csicsvari J, Buzsáki G (1999) Sustained activity of hippocampal pyramidal cells by ‘space clamping’ in a running wheel. Eur J Neurosci 11:344–352CrossRefPubMedGoogle Scholar
  6. 6.
    David G (1999) Mitochondrial clearance of cytosolic Ca2+ in stimulated lizard motor nerve terminals proceeds without progressive elevation of mitochondrial matrix [Ca2+]. J Neurosci 19:7495–7506PubMedGoogle Scholar
  7. 7.
    David G, Barrett EF (2000) Stimulation-evoked increases in cytosolic [Ca2+] in mouse motor nerve terminals are limited by mitochondrial uptake and are temperature-dependent. J Neurosci 20:7290–7296PubMedGoogle Scholar
  8. 8.
    David G, Barrett JN, Barrett EF (1997) Stimulation-induced changes in [Ca2+] in lizard motor nerve terminals. J Physiol (Lond) 504:83–96Google Scholar
  9. 9.
    David G, Barrett JN, Barrett EF (1998) Evidence that mitochondria buffer physiological Ca2+ loads in lizard motor nerve terminals. J Physiol (Lond) 509:59–65Google Scholar
  10. 10.
    Henkel AW, Lübke J, Betz WJ (1996) FM1–43 dye ultrastructural localization in and release from frog motor nerve terminals. Proc Natl Acad Sci 93:1918–1923CrossRefPubMedGoogle Scholar
  11. 11.
    Hirase H, Czurkó A, Csicsvari J, Buzsáki G (1999) Firing rate and theta-phase coding by hippocampal pyramidal neurons during ‘space clamping’. Eur J Neurosci 11:4373–4380CrossRefPubMedGoogle Scholar
  12. 12.
    Melamed-Book N, Rahamimoff R (1998) The revival of the role of the mitochondrion in regulation of transmitter release. J Physiol (Lond) 509:2Google Scholar
  13. 13.
    Morris RL, Hollenbeck PJ (1993) The regulation of bidirectional mitochondrial transport is coordinated with axonal outgrowth. J Cell Sci 104:917–927PubMedGoogle Scholar
  14. 14.
    Murthy VN (1999) Optical detection of synaptic vesicle exocytosis and endocytosis. Curr Opin Neurobiol 9:314–320CrossRefPubMedGoogle Scholar
  15. 15.
    Overly CC, Rieff HI, Hollenbeck PJ (1996) Organelle motility and metabolism in axons versus dendrites of cultured hippocampal neurons. J Cell Sci 109:971–980PubMedGoogle Scholar
  16. 16.
    Reuter H, Porzig H (1995) Localization and functional significance of the Na+/Ca2+ exchanger in presynaptic boutons of hippocampal cells in culture. Neuron 15:1077–1084PubMedGoogle Scholar
  17. 17.
    Ryan TA, Reuter H, Wendland B, Schweizer FE, Tsien RW, Smith SJ (1993) The kinetics of synaptic vesicle recycling measured at single presynaptic boutons. Neuron 11:713–724PubMedGoogle Scholar
  18. 18.
    Ryan TA, Reuter H, Smith SJ (1997) Optical detection of a quantal presynaptic membrane turnover. Nature 388:478–482CrossRefPubMedGoogle Scholar
  19. 19.
    Scotti AL, Chatton J-Y, Reuter H (1999) Roles of Na+-Ca2+ exchange and of mitochondria in the regulation of presynaptic Ca2+ and spontaneous glutamate release. Philos Trans R Soc Lond Ser B 354:357–364CrossRefGoogle Scholar
  20. 20.
    Shepherd GMG, Harris KM (1998) Three-dimensional structure and composition of CA3-CA1 axons in rat hippocampal slices: implications for presynaptic connectivity and compartmentalization. J Neurosci 18:8300–8310PubMedGoogle Scholar
  21. 21.
    Waters J, Smith SJ (2000) Phorbol esters potentiate evoked and spontaneous release by different presynaptic mechanisms. J Neurosci 20:7863–7870PubMedGoogle Scholar
  22. 22.
    Wiener SI, Paul CA, Eichenbaum H (1989) Spatial and behavioral correlates of hippocampal neuronal activity. J Neurosci 9:2737–2763PubMedGoogle Scholar
  23. 23.
    Zenisek D, Matthews G (2000) The role of mitochondria in presynaptic calcium handling at a ribbon synapse. Neuron 25:229–237PubMedGoogle Scholar

Copyright information

© Springer-Verlag  2003

Authors and Affiliations

  1. 1.Department of Molecular and Cellular Physiology, Beckman CenterStanford Medical SchoolStanfordUSA
  2. 2.Abteilung ZellphysiologieMax-Planck-Institut für medizinische ForschungHeidelbergGermany

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