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Cyclic AMP induces functional presynaptic boutons in hippocampal CA3–CA1 neuronal cultures

Nature Neuroscience volume 2, pages 24–30 (1999)Cite this article

Abstract

Long-term forms of synaptic plasticity that may underlie learning and memory have been suggested to depend on changes in the number of synapses between presynaptic and postsynaptic neurons. Here we have investigated a form of synaptic plasticity in cultures of hippocampal CA3 and CA1 neurons related to the late phase of long-term potentiation, which depends on cAMP and protein synthesis. Using the fluorescent dye FM 1-43 to label active presynaptic terminals, we find that a membrane permeable analog of cAMP enhances the number of active presynaptic terminals and that this effect requires protein synthesis.

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Figure 1: Sp-cAMPS increases the number of presynaptic boutons labeled in an activity-dependent manner.
Figure 2: Quantitation of changes in the mean number and intensity of boutons stained in an activity-dependent manner by FM 1-43.
Figure 3: Rp-cAMPS, anisomycin or glutamate antagonists prevent Sp-cAMPS from enhancing the number of active boutons.
Figure 4: Effects of inhibitors of the cAMP cascade, protein synthesis or glutamate receptors on the ability of Sp-cAMPS to enhance the number of active boutons.
Figure 5: Sp-cAMPS may recruit pre-existing, functionally silent boutons.
Figure 6: Comparison of changes in the mean number of boutons stained in an activity-independent and in an activity-dependent manner.

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Acknowledgements

We thank Kelsey Martin for help and advice throughout this project, Danny Baranes for help in initial experiments and Eric Odell for help with the figures. We also thank Craig Bailey, Vadim Bolshakov, Mary Chen, Bob Hawkins, Kelsey Martin and Paul Pavlidis for comments on the manuscript. This work was partially supported by a grant from NIH and HHMI.

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Authors and Affiliations

  1. Departments of Pharmacology, 722 W. 168 St., New York, 10032, New York, USA

    Li Ma & Steven A. Siegelbaum

  2. Departments of Physiology, Psychiatry and Biochemistry, 722 W. 168 St., New York, 10032, New York, USA

    Eric R. Kandel

  3. Departments of Center for Neurobiology and Behavior, 722 W. 168 St., New York, 10032, New York, USA

    Leonard Zablow, Eric R. Kandel & Steven A. Siegelbaum

  4. Departments of Howard Hughes Medical Institute, Columbia University, 722 W. 168 St., New York, 10032, New York, USA

    Li Ma, Leonard Zablow, Eric R. Kandel & Steven A. Siegelbaum

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Correspondence to Steven A. Siegelbaum.

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Ma, L., Zablow, L., Kandel, E. et al. Cyclic AMP induces functional presynaptic boutons in hippocampal CA3–CA1 neuronal cultures. Nat Neurosci 2, 24–30 (1999). https://doi.org/10.1038/4525

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