New ways of looking at synapses

  • Michael FrotscherEmail author
  • Shanting Zhao
  • Werner Graber
  • Alexander Drakew
  • Daniel Studer
Original Paper


Current concepts of synaptic fine-structure are derived from electron microscopic studies of tissue fixed by chemical fixation using aldehydes. However, chemical fixation with glutaraldehyde and paraformaldehyde and subsequent dehydration in ethanol result in uncontrolled tissue shrinkage. While electron microscopy allows for the unequivocal identification of synaptic contacts, it cannot be used for real-time analysis of structural changes at synapses. For the latter purpose advanced fluorescence microscopy techniques are to be applied which, however, do not allow for the identification of synaptic contacts. Here, two approaches are described that may overcome, at least in part, some of these drawbacks in the study of synapses. By focusing on a characteristic, easily identifiable synapse, the mossy fiber synapse in the hippocampus, we first describe high-pressure freezing of fresh tissue as a method that may be applied to study subtle changes in synaptic ultrastructure associated with functional synaptic plasticity. Next, we propose to label presynaptic mossy fiber terminals and postsynaptic complex spines on CA3 pyramidal neurons by different fluorescent dyes to allow for the real-time monitoring of these synapses in living tissue over extended periods of time. We expect these approaches to lead to new insights into the structure and function of central synapses.


Synapse structure High-pressure freezing Real-time microscopy Mossy fiber Dendritic spines 



These studies were supported by the Deutsche Forschungsgemeinschaft (SFB 505, project A3) to MF and AD and the Swiss National Foundation (Grant No.: 105822) to DS. We thank Sigrun Nestel and Cornelia Hofmann for excellent technical assistance.


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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Michael Frotscher
    • 1
    Email author
  • Shanting Zhao
    • 1
  • Werner Graber
    • 2
  • Alexander Drakew
    • 1
  • Daniel Studer
    • 2
  1. 1.Institute of Anatomy and Cell BiologyUniversity of FreiburgFreiburgGermany
  2. 2.Institute of AnatomyUniversity of BernBern 9Switzerland

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